concanavalin-a and Hodgkin-Disease

Over the past 5 years, parameters of immunological function have been determined in all children with biopsy-proven Hodgkin's disease in the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center. This report summarizes the in vitro responses of lymphocytes to stimulation by mitogens and antigens (between January 1975 and December 1976) in 33 of these previously untreated patients. In nine of these patients, responses of the splenic lymphocytes were studied concomitantly with the responses of peripheral blood lymphocytes. Peripheral blood from normal children and adults was used as the control. Our results have demonstrated no significant differences between the responses of normal children and adult controls. The absolute necessity for concomitant studies of the controls and the patients was shown. The value of examining multiple concentrations of a single mitogen was also well defined. In the children with Hodgkin's disease, there was a consistent failure of the peripheral blood lymphocytes to respond to the lower concentration dose of phytohemagglutinin. However, this abnormality was not found in the splenic lymphocytes.

Topics: Adolescent; Adult; Age Factors; Antigens; Antigens, Bacterial; Antigens, Fungal; Candida albicans; Child; Child, Preschool; Concanavalin A; Escherichia coli; Female; Hodgkin Disease; Humans; Lectins; Lymphocyte Activation; Male; Mitogens; Spleen; Staphylococcus aureus

Topics: Abrin; Agglutination; Animals; Antineoplastic Agents; Binding Sites; Cell Membrane; Cell Transformation, Neoplastic; Cells, Cultured; Concanavalin A; Glycoproteins; Hodgkin Disease; Humans; Immunity, Cellular; In Vitro Techniques; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Neoplasms; Receptors, Drug; Ricin

PICOT was originally discovered as a protein kinase C (PKC) binding protein in human Jurkat T-lymphocytes in which it was found to modulate PKCtheta-dependent functions. In addition, RT-PCR analysis suggested the expression of PICOT in a wide range of organs and cell types, including cells that are devoid of PKCtheta. We aimed at analyzing the expression of the PICOT protein in mouse lymphoid organs, and to compare them with those of Jurkat T-lymphocytes and other cell lines. We also analyzed whether PICOT expression in T-lymphocytes is dependent on the presence of PKCtheta, and whether it correlates with cell growth rate. Western blot analyses demonstrated PICOT expression in all lymphoid organs and cell lines tested. In addition, similar expression levels were observed in lymphoid organs of wild-type and PKCtheta-null mice, suggesting that PICOT expression in T-lymphocytes is independent of PKCtheta. However, PICOT expression levels were higher in Jurkat T-lymphocytes and other lymphoma cell lines compared to freshly isolated lymphocytes, while T-lymphocyte mitogens, such as concanavalin A, increased PICOT expression concomitantly with the induction of a faster T-lymphocyte growth rate. Finally, immunohistochemistry of freshly-isolated lymph nodes from Hodgkin's lymphoma patients revealed significantly higher levels of PICOT in Hodgkin's cells, compared to the normal surrounding lymphocytes. The present results show a direct correlation between PICOT expression levels and increased cell growth, both in vitro and in vivo, and suggest that immunostaining of PICOT might be useful for in situ identification of transformed cells, such as those of Hodgkin's lymphoma.

Topics: Animals; Carrier Proteins; Cell Line, Transformed; Concanavalin A; Female; Hodgkin Disease; Humans; Isoenzymes; Jurkat Cells; Lymph Nodes; Male; Mice; Mice, Knockout; Protein Kinase C; Protein Kinase C-theta; RNA, Messenger; Spleen; T-Lymphocytes; Thymus Gland

Genetic factors are known to be important in the development of Hodgkin lymphoma (HL). Interleukin-10 (IL-10) secretion by both malignant and reactive cells is thought to be important in the pathogenesis of HL especially Epstein-Barr virus (EBV) positive cases. Polymorphisms of the IL-10 gene have been reported to be associated with susceptibility to EBV infection. The cytotoxic response to EBV is determined by a Th1 biased immune response which is characterised by interferon gamma (IFNgamma) secretion. We therefore investigated polymorphisms in the IL-10 (-1082 G/A and -592 C/A) and IFNgamma (intron 1 CA repeat) genes as predisposing factors in the development 147 cases of HL. A difference of borderline statistical significance was demonstrated for the IFNgamma gene polymorphism but significance was lost when analysis was restricted to the common genotypes. No significant differences in the distributions of genotypes were found for the IL-10 gene polymorphisms. IL-10 and IFNgamma levels were also measured on 26 patients with HL. No statistically significant differences were detected when the results were analysed by genotype. We found little evidence IL-10 and IFNgamma genotypes predispose to the development of HL or influence the inflammatory host response.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Concanavalin A; Female; Genotype; Haplotypes; Herpesvirus 4, Human; Hodgkin Disease; Humans; Inflammation; Interferon-gamma; Interleukin-10; Introns; Male; Middle Aged; Polymorphism, Genetic

Indirect data supporting a preexisting immunologic impairment in patients with Hodgkin's disease (HD) have been presented in recent years. These immunologic defects are supposed to be related to genetic and/or environmental factors. In this study, 65 first-degree relatives and 12 spouses of 21 consecutive patients with HD were studied immunologically. Furthermore, seven twin pairs in which one partner had HD and four additional nonmatched healthy co-twins were also included in the study. A decreased lymphocyte DNA synthesis induced by Concanavalin A, a high spontaneous DNA synthesis, or a low CD4+/8+ ratio was found in 21 (32%) consanguineous, two (17%) nonconsanguineous relatives, and five (50%) healthy co-twins. The corresponding figures for the untreated patients with HD and the control series were 14 of 21 (65%) and 21 of 127 (16%), respectively. Total lymphocyte counts or lymphocyte subpopulations did not differ between HD relatives and controls. The increased frequency of blood lymphocyte defects among consanguineous first-degree relatives favors the existence of a genetically determined immune deficiency in at least a proportion of apparently healthy relatives of patients with HD. However, nongenetic factors such as age and environment may add to the defect.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Concanavalin A; DNA; Family Health; Female; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Lymphocytes; Male; Middle Aged; Twins

Antibodies directed against the human T cell receptor or the closely associated CD3 molecule stimulate polyclonal T cell proliferation via mechanisms that mimic a primary immune response. We have investigated the requirement for IL-1 production in anti-CD3 (OKT3)-mediated mitogenesis using a Hodgkin's disease cell line (L428) as the accessory cell. L428 cells did not produce detectable IL-1 following stimulation with lipopolysaccharide or phorbol ester (PMA), nor did they transcribe detectable levels of mRNA for IL-1 alpha or beta after such treatment. Despite their inability to produce IL-1, as few as 1 X 10(4) L428 cells reconstituted the proliferative response of accessory cell-depleted T cells to anti-CD3. Although larger numbers of non-rosette-forming (E-) cells were required for maximal responsiveness to anti-CD3, the maximal degree of proliferation was higher with E- cells than with L428 cells. L428-mediated T cell proliferation did not result from residual accessory cells in the responding population or an allogeneic effect since L428 cells were also capable of providing accessory cell activity for the anti-CD3-dependent generation of IL-2 by the Jurkat T cell line. Although the mechanism by which L428 cells provide accessory functions remains incompletely characterized, the ability of anti-HLA-DR F(ab')2 fragments to completely abrogate L428 and monocyte-mediated anti-CD3 mitogenesis, despite the addition of exogenous IL-1, provides evidence for the participation HLA-DR molecules in this response. These data indicate that anti-CD3-induced proliferation of unprimed human T lymphocytes can occur independently of IL-1 production by accessory cells and may involve the participation of HLA-DR molecules.

Topics: Antibodies, Monoclonal; Antigen-Presenting Cells; Antigens, Differentiation, T-Lymphocyte; CD3 Complex; Cell Separation; Concanavalin A; HLA-DR Antigens; Hodgkin Disease; Humans; Interleukin-1; Interleukin-2; Leukocytes, Mononuclear; Lymphocyte Activation; Receptors, Antigen, T-Cell; RNA, Messenger; T-Lymphocytes; Tumor Cells, Cultured

In this study we evaluated some immunological features in both patients and healthy relatives within five families with multiple cases of Hodgkin's disease (HD). Such familial groups (at 'high risk' of HD), represent, in our opinion, a suitable opportunity to investigate the role of immune-deficiency in HD. The results obtained in the patient group confirm the well known persistent immune derangement in long term HD survivors. Regarding the group of relatives, we found a pattern similar to that of the patients. In particular, a decrease in the T helper lymphocyte subset and a lower response to Con-A mitogen were detected, which were statistically significant. These findings, confirmed in other studies of multiple case families, could support the hypothesis of a preexisting immune-deficiency in HD. This in turn would greatly contribute towards a better understanding of the role of immune-deficiency in the etiopathogenesis of the disease.

Topics: Adolescent; Adult; Aged; Concanavalin A; Female; Hodgkin Disease; Humans; Immune Tolerance; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Pedigree; Phytohemagglutinins

The lymphoid tissues from patients with infectious mononucleosis or, less frequently, with other reactive conditions may contain Reed-Sternberg (RS)-like cells. These tissues also contain cells resembling the lacunar cells or lymphocytic/histiocytic (L/H) variants, which are present in the lymphocyte-predominant type of Hodgkin's disease. The phenotype of these RS- and L/H-like cells was determined with a large panel of antibodies and lectins. The cells expressed sialylated Leu-M1, Con A, LN-2, and, less frequently, interleukin-1, S-100, and peanut agglutinin receptor. They reacted negatively with two markers for RS cells, Ki-1 and HeFi-1. These RS-like cells were consistently negative for T- and B-cell markers, including immunoglobulins. The markers of the RS-like cells are distinctly different from those in B-immunoblasts, but closely resemble those in interdigitating reticulum cells. It is concluded that interdigitating reticulum cells, when stimulated, can be transformed into lacunar-, L/H-, or RS-like cells.

Topics: Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Concanavalin A; Histiocytes; Hodgkin Disease; Humans; Infectious Mononucleosis; Interleukin-1; Lymphocytes; Lymphoid Tissue; Phenotype; S100 Proteins

Morphologic variations of Concanavalin A-binding histiocytes were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (72 asymptomatic, and 68 with constitutional symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Three morphologic types of stromal histiocytes were recognized: medium-sized cells similar to those seen in reactive follicles, characterized by distinct cytoplasm and cell borders, and uniform nuclei (Type A); damaged-appearing Type A cells marked by rarefied or ragged cytoplasm, disrupted or indistinct cell borders, and varying sized nuclei (Type B); and large spindling or stellate cells (Type C). Type A cells were predominant in 52 patients; Type B cells in 51; Type C cells in seven; and Type A cells were mixed with Type B in 30. Fever was present in one of 52 patients (1.9%) with Type A predominance; 43 of 51 (84.3%) with Type B cell predominance; none of seven (0%) with Type C predominance; and 13 of 30 (43.3%) with mixed Type A and B cells. Logistic regression analysis of the data showed that the association of fever with Type B cell predominance was highly significant, and was not attributable to the known association of fever with other variables. Morphologic evidence suggests that fever in Hodgkin's disease may be a clinical manifestation of damaged macrophage-histiocytes rather than an acute-phase response of inflammatory or immune reaction.

Topics: Adolescent; Adult; Biopsy; Concanavalin A; Female; Fever; Histiocytes; Histocytochemistry; Hodgkin Disease; Humans; Macrophages; Male; Middle Aged

Staining with Concanavalin agglutinin (Con A) reveals a far greater number of macrophage-histiocytes (M-H) in paraffin sections than any other staining method. With Con A staining, the shapes of stromal M-H are clearly visualized, thus enabling a study of their morphologic variations. Con A staining patterns were also unchanged in specimens left at room temperature for 24 to 28 hours before fixation. The appearance of Con A-binding histiocytes was studied in tumors, recurrent as well as original, of 18 patients with biopsy-proven early relapse (within 26 months of diagnosis), and compared with those of 26 patients who were in complete remission (lasting 48 months at the minimum). The early-relapse patients were diagnosed from 1977 through 1984, and all received intensive combination chemotherapy. The relapse-free patients were treated in various manners, and included six patients diagnosed in the 1960s who were treated with radiation alone. Three forms of Con A-binding histiocytes were easily recognized: medium-sized cells similar to those seen in reactive follicles, characterized by uniform nuclei and distinct, abundant cytoplasm (Type A); cells of varying size and shape with altered cytoplasm, rarefied and ragged with indistinct cell borders, or globular (Type B); and large cells, stellate or spindling (Type C). Large numbers of Type A cells were present in all tumors of the relapse-free patients but were virtually absent in the original and recurrent tumors of the early-relapse group. Conversely, Type B cells were rare in the relapse-free group, but were the most common type in the patients with early relapse. Type C cells were not seen in the former group, but were present in the latter. These observations suggest that the morphologic variations of Con A-binding histiocytes in Hodgkin's disease are associated with tumor behavior. Con A staining, which can best depict stromal histiocytes in paraffin sections, may be used to identify patients at a high risk of early relapse.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Concanavalin A; Female; Fixatives; Histiocytes; Histocytochemistry; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Palatine Tonsil; Prognosis; Staining and Labeling; Time Factors

The effects of BM 12 531, a 2-cyanaziridinyl derivative, on in vitro generation of Con A induced suppressor cells as well as generation of spontaneous suppressor cells in peripheral blood lymphocytes of 9 chronic myeloid leukemia (CML) patients in remission, 9 patients with active Hodgkin's disease (HD) and 12 normal healthy donors were studied. The suppressor cells generated spontaneously and with Con A, in the presence and absence of the drug, were tested for their modulating effect on mitogenic (PHA) response of autologous lymphocytes. The results indicate that the addition of the drug at the time of generation of suppressor cells decreased the spontaneous suppressor cell activity in 2/4 healthy donors, 3/7 CML patients and 4/6 HD patients. Con A induced suppressor cell activity generated in presence of the drug was significantly reduced in 7/12 healthy donors, 6/9 CML patients and 3/9 HD patients.

Topics: Aziridines; Azirines; Cells, Cultured; Concanavalin A; Hodgkin Disease; Humans; Leukemia, Myeloid; Lymphocyte Activation; T-Lymphocytes, Regulatory

Expression of class II major histocompatibility (MHC) antigens by peripheral blood monocytes from 12 patients with Hodgkin's disease (HD) were studied employing antiserum and complement-mediated cytotoxicity. Overall, the expression of class II MHC antigens was significantly decreased on HD monocytes (cytotoxicity index [C.I.] = 60.2 +/- 5.8% vs 77.6 +/- 2.8%, P less than .02). This decrease was most marked in patients with more severe disease. In fact, mean alloantigen expression for patients with advanced stages of disease was 58% of that observed in controls. The number of human lymphocyte antigen (HLA)-DR antigenic sites per cell was also reduced as determined by monoclonal anti-DR antibody and FACS analysis. There was 38% more HLA-DR per cell in normal controls than in moderately advanced Hodgkin's patients. Class II MHC antigen expression on HD monocytes were increased partially by an IFN-gamma containing concanavalin A-stimulated human mononuclear cell culture supernatants (Con A sup), although remaining subnormal. When monocytes were cultured with Con A sup and indomethacin, alloantigen expression was increased in HD and control monocytes, but indomethacin failed to normalize class II MHC antigen expression on HD monocytes (C.I. = 72.3 +/- 4.7% vs 90.2 +/- 1.8%, P less than .01). We conclude that PGE accounts only inpart for the decreased alloantigen expression by HD monocytes. Interleukin (IL) 1 production by patients' monocytes was not reduced as compared to normals and therefore does not contribute to the decreased MHC II antigen expression. Decreases in alloantigen expression may be an important determinant of the T cell-mediated immune abnormalities in Hodgkin's disease.

Topics: Adult; Concanavalin A; Female; Histocompatibility Antigens Class II; HLA-DR Antigens; Hodgkin Disease; Humans; Indomethacin; Interleukin-1; Leukocyte Count; Male; Middle Aged; Monocytes; Prostaglandins E

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was purified from 3 liters of serum-free conditioned medium of the Hodgkin's tumor cell line L428 KSA. The conditioned medium contained a high specific activity of 2.5 X 10(5) units of total colony-stimulating factor per mg protein. Colony-stimulating factor activity was determined by colony formation by human fetal liver cells or mouse bone marrow cells. The latter bioassay discriminated colony-stimulating factor 1, a subclass specific for monocyte/macrophage production, and G-CSF, specific for granulopoiesis, from GM-CSF. The starting material contained predominantly GM-CSF with CSF-1 and G-CSF constituting 10% and 12%, respectively, of the total activity. A seven-stage purification scheme was employed. The first stage involved concentration by batch chromatography on calcium phosphate gel. Subsequent stages involved gel filtration on Ultrogel AcA44, affinity chromatography on concanavalin A-Sepharose, batch chromatography on calcium phosphate gel and high-performance liquid chromatography on C1 reversed-phase (TSK TMS-250), gel permeation and C8 reversed-phase columns. The purified material showed a single disperse band, having an Mr of 30,000, by silver staining on sodium dodecyl sulfate polyacrylamide gel electrophoresis. An amino-terminal sequence of 20 amino acids was determined in a gas-phase sequencer with 500 ng of purified material. The sequence was identical to that predicted from the cDNA sequence. It was active on human fetal liver cells with half-maximum colony formation at 1 X 10(-12) M, but was not active on mouse bone narrow cells.

Topics: Amino Acid Sequence; Cell Line; Chromatography, Affinity; Colony-Stimulating Factors; Concanavalin A; Culture Media; DNA; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Hodgkin Disease; Humans; Interleukin-3; Liver; Molecular Weight; Neoplasm Proteins

The patients with Hodgkins disease possessed an increased number of the T gamma-cells, a decreased number of T mu cells and higher endogenic suppressor activity as compared with healthy donors. Subpopulation of ferritin-carrying lymphocytes was found only in patients, whereas in donors these cells were not revealed at all. It was shown that ferritin receptors expressed only on T gamma-cells. For determination of the functional role of T-cell subpopulation before and after Con-A stimulation were studied. The suppression activity correlated with the T gamma-cell levels.

Topics: Adult; Cell Membrane; Child; Concanavalin A; Culture Media; Ferritins; Hodgkin Disease; Humans; In Vitro Techniques; Leukocyte Count; Lymphocyte Activation; Rosette Formation; T-Lymphocytes; T-Lymphocytes, Regulatory

The origin of the Reed-Sternberg cells of Hodgkin's disease is controversial with proponents of transformed lymphocyte and macrophage histiocyte derivations. Lectin receptors are potentially useful new cell markers in the investigation of lymphoproliferative disease. In this study, the lectin-binding properties of the Reed-Sternberg cell were investigated in an effort to clarify the cell of origin. Utilizing a simple peroxidase technique applicable to formalin-fixed, paraffin-embedded tissue, lectin binding was studied in 13 cases of Hodgkin's disease. Reed-Sternberg cells were found to bind cytoplasmic concanavalin A, but not Arachis hypogaea (peanut agglutinin) or Lotus tetragonolobus (asparagus pea). These are the lectin-binding properties of macrophage histiocytes rather than transformed lymphocytes. Lectin-binding studies support the macrophage origin of the neoplastic cells of Hodgkin's disease.

Topics: Adolescent; Adult; Aged; Child, Preschool; Concanavalin A; Female; Histiocytes; Hodgkin Disease; Humans; Lectins; Macrophages; Male; Middle Aged; Monocytes; Peanut Agglutinin; Plant Lectins; Receptors, Concanavalin A; Receptors, Mitogen; Staining and Labeling

Indirect evidence suggests that abnormal regulation of B cells exists in Hodgkin's disease (HD) due, perhaps, to the sequestration of regulatory T-lymphocyte subpopulations in the spleen in this condition. Other work implicates the B-cell itself in this abnormality. In this study we have attempted to measure regulatory T-cell function by quantitating spontaneous and Concanavalin A(Con A)-induced suppressor activity in T-enriched spleen cells from control and HD spleens for pokeweed mitogen(PWM)-induced immunoglobulin (Ig) production. Using this polyclonal system, HD patients' spleen T-lymphocytes could not be shown to differ markedly from the control series. Cells capable of spontaneous and mitogen-induced modulation of Ig synthesis were present in both populations and showed a reciprocal relationship implying the activation of the same cell type. In this respect HD and control spleen resembled peripheral blood. A limited parallel investigation of PWM-regulatory activity in cells from spleen and peripheral blood from individual patients was also undertaken. Individual patients showed wide variation in suppression between the two compartments and, therefore, measurements of functional capacity in blood alone may not provide a true estimate of total regulatory capacity in lymphoma patients.

Topics: B-Lymphocytes; Cell Survival; Concanavalin A; Hodgkin Disease; Humans; Immunoglobulins; Lymphocyte Activation; Pokeweed Mitogens; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory

Sixty-three patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) were studied to analyze the mechanisms responsible for impaired in vitro lymphocyte reactivities to the mitogen concanavalin A. Lymphocytes from 43 of the 52 untreated patients acquired enhanced in vitro responsiveness after preculturing in media alone for 3 days. However, 38 of the untreated patients failed to achieve entirely normal lymphocyte responses after preculturing . Suppressor cells were detected in 25 patients, but the intensity of suppression was much less than expected when compared with the severity of in vitro impairments. Suppressor activity did correlate with certain clinical characteristics in NHL, whereas no correlation was observed for HD. In contrast to the untreated patients, successfully treated patients demonstrated either normal responses or profound, irreversible impairments. The data indicate that several mechanisms which usually coexist can contribute to the impaired in vitro lymphocyte responses in untreated HD and NHL, and that a single, irreversible type of mechanism explains the impaired reactivities in successfully treated patients.

Topics: Adult; Cell Division; Cells, Cultured; Concanavalin A; Female; Hodgkin Disease; Humans; Lymphocyte Culture Test, Mixed; Lymphoma; Male; Middle Aged; Monocytes; T-Lymphocytes, Regulatory

Purified human peripheral blood T cells that have been depleted of Ia-bearing cells and adherent cells do not proliferate in response to concanavalin A. The addition of as few as 1% radiated L428 tumor cells restores the proliferative capacity of the T cells. The L428 cell line is a long-term tissue culture line of Reed-Sternberg cells obtained from a patient with Hodgkin's disease. The proliferation of the T cells plus the L428 cells follows the same kinetics and has the same response to varying doses of mitogen as either unfractionated mononuclear leukocytes or purified T cells plus allogeneic adherent cells. The L428 cells are 30 times more potent as accessory cells than allogeneic adherent cells. The accessory cell function of the L428 cells is not blocked in cultures containing anti-Ia antibody. Neither supernatant from the L428 cell cultures nor human IL 1 replaces the accessory cells. The ability of the L428 cells to restore the proliferative capacity of purified T cells isolated from patients with active Hodgkin's disease was also studied. Patients with early stages of the disease had normal proliferative responses in the presence of the L428 accessory cells. However, the proliferative response of the poor prognosis, advanced-stage patients was reduced as compared to age- and sex-matched controls, supporting a deficit in their T cell function. The L428 tumor cells share many properties such as accessory cell function, morphology, and cell surface markers with the dendritic cells described in animal and human systems.

Topics: Adult; Antibodies, Monoclonal; Cell Line; Cell Transformation, Neoplastic; Concanavalin A; Dose-Response Relationship, Immunologic; Histocompatibility Antigens Class II; Hodgkin Disease; Humans; Interleukin-1; Kinetics; Lymphocyte Activation; Lymphocyte Cooperation; Male; Middle Aged; T-Lymphocytes

The occurrence and staining patterns of Concanavalin A (Con A) binding histiocytes were studied in diagnostic lymph node specimens of 133 patients with Hodgkin's disease. Varying numbers of Con A binding histiocytes were present in all tumors. Two distinct cytoplasmic staining patterns of the Con A binding histiocytes were noted: diffuse, and a pattern termed "globular" which represents a dense, solitary paranuclear aggregate of binding sites. The diffuse binding pattern was seen in the majority of histiocytes with no apparent nuclear atypia, but was also occasionally seen in Reed-Sternberg cells. Globular binding was present in both benign and malignant-looking histiocytes, including rare Reed-Sternberg cells. Based on the number of histiocytes in which globular binding of Con A (G-cells) was observed, tumors were grouped in the following three categories: Group 1: tumors with large numbers of G-cells (42 cases); Group 2: tumors with a small number of G-cells (16); and Group 3: tumors with rare or no G-cells (75). Tumors with large numbers of G-cells were seen more frequently in patients with disseminated disease than in those with localized (69.0% versus 31.0%; P less than or equal to 0.002), and more often in patients with B-symptoms than in those without (73.8% versus 26.2%; P less than or equal to 0.001). Large numbers of G-cells were present in most tumors of the lymphocyte depletion type (14/16), whereas rare or no G-cells were seen in the majority of the nodular sclerosis type (46/59). These observations suggest that the G-cells may represent an abnormal variant of histiocytes, the occurrence of which is associated with unfavorable clinical and pathologic features of Hodgkin's disease.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Female; Histiocytes; Hodgkin Disease; Humans; Lymph Nodes; Macrophages; Male; Middle Aged

When stained for reactive sialyl groups with fluorescein-labelled Aprotinin (FLA), lymphocytes of three diffuse lymphomas were uniformly faintly fluorescent. The nodules of a nodular lymphocytic lymphoma showed dimly fluorescing lymphocytes surrounded by brightly fluorescing, apparently normal cells. The spleens of eight patients with Hodgkin's disease showed involvement in six cases. With FLA, the two uninvolved spleens contained only brightly fluorescing lymphocytes, whereas the foci of Hodgkin's lesions in the six spleens and in eight involved lymph nodes from a further eight patients contained varying proportions of brightly and dimly fluorescing lymphoid cells. Mononuclear Hodgkin's cells and bi- or multinucleated Reed-Sternberg cells fluoresced faintly. Fluorescein-labelled Ricinus communis agglutinin (FL-RCA) for galactose, and Concanavalin A (FL-Con A) for mannose or glucose, showed eosinophils, reticulin and collagen fibres especially in nodular sclerosing Hodgkin's disease, whereas all lymphocytes, Hodgkin and Reed-Sternberg cells stained faintly with either lectin. The reduction of reactive sialyl groups in malignant lymphocytes of lymphomas and Hodgkin's lesions is similar to that in lymphocytic leukaemias. It is suggested that in Hodgkin's disease these lymphocytes together with the Hodgkin and Reed-Sternberg cells represent the malignant component, whereas the brightly fluorescent normal lymphocytes, together with histiocytes, eosinophils (and neutrophils) represent a reactive component in the lesions. Similarly, the reactive lymphocytes in sarcoid lesions and sinus histiocytosis were brightly fluorescing.

Topics: Aprotinin; Bone Marrow; Concanavalin A; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Lectins; Lymph Nodes; Lymphocytes; Lymphoma; Plant Lectins; Sialic Acids; Spleen; Staining and Labeling

Untreated patients with Hodgkin's disease are known to have significant impairment of cellular immunity. Recent studies have demonstrated that effector T cells from these patients have increased sensitivity to the suppression mediated by two normal immunoregulatory cells, ie, suppressor monocytes and suppressor T cells. Thus, increased sensitivity to suppression may be a common cause of multiple abnormalities of cellular immunity. Patients achieving long-term disease-free survival after chemotherapy have also been studied. Although they are no longer anergic, they have persistent reductions in peripheral blood E rosettes and T cell proliferation. Increased sensitivity to suppressor monocytes and T cells also persists. These abnormalities do not appear to be caused by the treatment since they were not detected in diffuse histiocytic lymphoma patients surviving after similar chemotherapy. Immunologic studies in family members are required to determine whether these abnormalities are a permanent immunologic deficit acquired only with the development of Hodgkin's disease or an inherited characteristic that predisposes a patient to develop Hodgkin's disease.

Topics: Concanavalin A; Hodgkin Disease; Humans; Immunity, Cellular; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphoma; T-Lymphocytes; T-Lymphocytes, Regulatory

We have studied the function of T cells in the peripheral blood obtained from long term survivors with Hodgkin's disease in order to determine the sensitivity of those T cells to normal suppressor cell immunoregulatory mechanisms. Concanavalin A-activated suppressor cells from normal donors suppressed the proliferation of lymphocytes obtained from 11 patients (56.8 +/- 3.5 percent) and from 28 allogeneic normal control subjects (39.8 +/- 2.7 percent [p less than 0.001]). When suppressor monocytes from the normal donors were studied, the mean proliferation of lymphocytes from 19 patients was suppressed 76.3 +/- 4.8 percent whereas proliferation of lymphocytes from 26 normal donors was suppressed 46.6 +/- 4.4 percent (p less than 0.0001). There was no tendency for the increased sensitivity to suppression that was observed in either assay system to return to normal as the patients' disease free interval increased from 1.5 years to 12 years. Furthermore, long-term survivors with diffuse histiocytic lymphoma, who had been treated with comparable chemotherapy, had normal sensitivity to the suppressor monocytes (45.1 +/- 3.8 percent). In Hodgkin's disease, the persistent increased sensitivity of T cells to two different normal immunoregulatory cells suggests that the response of the T cell to regulatory signals may be an important cause of the depressed cellular immunity observed in Hodgkin's disease and a clue to the etiology of the disease.

Topics: Concanavalin A; Hodgkin Disease; Humans; Immunosuppression Therapy; Lymphocyte Activation; Monocytes; T-Lymphocytes; T-Lymphocytes, Regulatory; Time Factors

The effect of sera from patients with Hodgkin's disease (HD) on monocyte dependent ConA and MLC-activation of normal lymphocytes to DNA synthesis was studied. Lymphocyte stimulation was greatly enhanced in the presence of monocytes at a monocyte : lymphocyte ratio of less than or equal to 8 : 1. Higher ratios were usually suppressive. Some HD sera suppressed monocyte mediated enhancement of ConA and MLC-stimulation efficiently. The degree of inhibition by the individual HD serum remained similar in the absence of monocytes and at various monocyte : lymphocyte ratios. Pretreatment of monocytes or lymphocytes with HD serum had no effect. Inhibition was only noted when serum was present during the whole culture period. It is concluded that HD sera do not hamper the activity of monocytes to augment lymphocyte growth. The effect may be explained by direct effects of serum factors on lymphocytes.

Topics: Concanavalin A; Hodgkin Disease; Humans; Immune Tolerance; In Vitro Techniques; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Monocytes

In the present study the number of E-RFC and the in vitro response to PHA and ConA were determined for lymphocytes obtained from spleens and lymph nodes of untreated HD patients. The results were correlated with tissue involvement and with the histological pattern of the disease. Our investigation has revealed: (1) involved spleens and lymph nodes contained a higher percentage of T-lymphocytes than uninvolved tissues. The differences was statistically significant for lymph nodes. (2) A statistically significant correlation was not found between T-lymphocyte numbers and histology. (3) Lymphocytes from uninvolved spleens were significantly more reactive to both mitogens than cells from involved spleens and control non-neoplastic spleens as well. (4) Similar results were obtained with lymph node lymphocytes; however, a significant difference was observed only when cells were stimulated with ConA. (5) The difference in proliferative response between uninvolved and involved tissues was maximally expressed in MC and progressively decreased in NS and LP. (6) T-cell enrichment does not alter the difference between uninvolved and involved spleens. (7) Cells from uninvolved and involved spleens, cultured for 24 hours, maintained unchanged their proliferative capacity. In this study evidence is provided that in HD T-lymphocytes from uninvolved tissues are characterized by an increased reactivity in mitogens, whereas cells from involved tissues are normally responsive.

Topics: Adolescent; Adult; Cell Division; Cells, Cultured; Child; Child, Preschool; Concanavalin A; Female; Hodgkin Disease; Humans; Lymph Nodes; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Spleen; T-Lymphocytes

In this study of 127 previously untreated adult patients with Hodgkin's disease and 167 age- and sex-matched controls, highly purified blood lymphocytes were studied for E+ receptors; their spontaneous DNA synthesis and that induced by concanavalin A, pokeweed mitogen, or purified protein derivative of tuberculin were measured as incorporation of 14C-thymidine. T-cell counts and the response to mitogens and antigen were significantly decreased in the patients, while the spontaneous lymphocyte activity was increased. Forty-nine patients had died after a mean observation time of 6 years. In these patients, there had been an increase in spontaneous DNA synthesis and a decrease in that induced by mitogens and antigen. These differences also remained significant when patients who died were compared with surviving patients in stages I-II. The 5-year survival rate of "bad immunology" patients was 30% as compared to 80% for the remainder. We suggest that these lymphocyte tests should be considered in an "immunologic staging system," which may give guidance in the future management of patients with Hodgkin's disease.

Topics: Adolescent; Adult; Aged; Concanavalin A; Female; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Pokeweed Mitogens; Rosette Formation; Skin Tests

Monocyte functions were studied in 16 patients with Hodgkin's disease, 11 untreated and five in unmaintained complete remission. Eleven untreated patients with non-Hodgkin's lymphomas and 21 healthy persons were used as controls. Monocytes were isolated from peripheral blood and enriched to greater than 90%. Lymphoma monocytes showed normal ability to lyse human RBC coated with anti-D IgG antibodies as evaluated by a 51Cr-release assay. The ability of monocytes to augment or suppress concanavalin A stimulation of lymphocytes purified to greater than 98% was studied by incubation of a number of lymphocytes with increasing amounts of purified monocytes. The incorporation of 14C-thymidine was potentiated by a factor of 10 in the presence of equal amounts of monocytes. There was no difference between monocytes from Hodgkin, non-Hodgkin or healthy controls to augment patients' autologous or normal lymphocytes. Patient monocytes also suppressed the response at the same monocyte-lymphocyte ratio as normal monocytes. Stimulation of patient lymphocytes without the addition of monocytes was usually lower than that of normal control lymphocytes. The difference between patient and control lymphocyte stimulation was preserved in the presence of monocytes. It is concluded that monocytes from patients with active Hodgkin's disease or non-Hodgkin's lymphoma have normal helper and suppressor effects on patient or normal lymphocytes stimulated by Con A and normal antibody-dependent cytotoxicity.

Topics: Antibody-Dependent Cell Cytotoxicity; Concanavalin A; Hemolysis; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphoma; Monocytes; Phagocytosis

Spleen lymphocytes from five patients with Hodgkin's disease (HD) type mixed cellularity and five normal controls were studied. An increased percentage of 'null cells' was observed in three out of the five patients studied. The two other patients had increased percentage of T lymphocytes. Lymphocytes from spleen with HD had a decreased ability to respond to suboptimal concentrations of T cell mitogens. When these cells were fractionated in a discontinuous density gradient a subpopulation of cells, unable to respond to Con A, was recovered from the dense cell fractions. The implications of the present findings to the understanding of the physiopathological changes in HD are discussed.

Topics: Adolescent; Adult; Cells, Cultured; Centrifugation, Density Gradient; Child; Concanavalin A; Dose-Response Relationship, Drug; Female; Hodgkin Disease; Humans; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Lymphocytes, Null; Male; Phytohemagglutinins; Rosette Formation; Spleen

Topics: Adolescent; Adult; Cell Adhesion; Concanavalin A; Female; Hodgkin Disease; Humans; Indomethacin; Lymphocytes; Male; Middle Aged; Mitomycins; T-Lymphocytes, Regulatory

Topics: Adult; Concanavalin A; Female; Hodgkin Disease; Humans; Immunity, Cellular; Immunologic Capping; Lymphocyte Activation; Male; Phytohemagglutinins; T-Lymphocytes; T-Lymphocytes, Regulatory

Serum IgE levels were evaluated in 119 untreated and 112 treated patients with Hodgkin's disease (HD). 38 of the nonatopic untreated patients showed significantly increased (> 300 IU/ml) IgE concentrations. No relationship could be found between increased IgE levels and depressed lymphocyte response to phytohemagglutinin (PHA) or the imbalance of TM and TG lymphocyte subsets. On the other hand, the mean level of suppressor activity elicitable from cells of untreated HD patients by concanavalin A preincubation did not differ significantly from that of healthy control subjects. In contrast, in treated patients, where there was a significant reduction in the number of circulating T lymphocytes, a further depression of the lymphocyte response to PHA, a more marked disproportion of TM and TG cell subsets and a noticeable fall in IgE concentration was found. These data suggest that increased IgE concentrations seen in untreated patients with HD are unrelated to the T-cell defects. They also suggest that hyperproduction of IgE is probably not invariably a consequence of a suppressor cell deficiency.

Topics: Cell Division; Concanavalin A; Hodgkin Disease; Humans; Immunoglobulin E; Lymphocytes; Lymphoma; T-Lymphocytes

Blood lymphocytes from 10 untreated patients with active Hodgkin's disease were compared with those of 10 cured patients with regard to the responsiveness of the cells to PHA and Con A following in vitro irradiation. Lymphocytes of patients remaining in long-term remission exhibited the same pattern of radiosensitivity as those of healthy donors: there was one relatively radiosensitive cell population and one relatively resistant. The latter cell population was undetectable in patients with an active disease. Reappearance of the radioresistant PHA and Con A reactive cell fractions might thus be associated with remission.

Topics: Adult; Aged; Cells, Cultured; Concanavalin A; Dose-Response Relationship, Radiation; Hodgkin Disease; Humans; Lymphocyte Activation; Middle Aged; Remission, Spontaneous

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of

Topics: Antigen-Antibody Complex; Antigens, Neoplasm; Binding Sites; Cell Transformation, Neoplastic; Cells, Cultured; Concanavalin A; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Kinetics; Retroviridae; T-Lymphocytes, Regulatory

Various immunological parameters were evaluated in untreated Hodgkin's patients before and after sensitization with dinitrochlorobenzene (DNCB). The ratio (r) of these parameters after/before DNCB sensitization for patients and second/first samples in the controls were calculated. There were significantly more patients in the r greater than 1.1 group for PHA and Con A responses and for peripheral blood T cell percentages. These data suggest that DNCB sensitization may have a nonspecific immunopotentiation effect.

Topics: Antibody Formation; B-Lymphocytes; Concanavalin A; Dinitrochlorobenzene; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Lymphocyte Activation; Nitrobenzenes; Phytohemagglutinins; Stimulation, Chemical; T-Lymphocytes

Peripheral blood lymphocytes from six untreated patients with Hodgkin's disease were exposed to various doses of ionizing radiation in vitro and thereafter tested for reactivity to PHA and ConA using DNA synthesis as a marker of viability. While the responsiveness of Hodgkin's disease lymphocytes was abolished by moderate radiation doses, the proliferative activity of healthy controls' lymphocytes was reduced in a biphasic fashion suggesting the presence of one relatively radiation-sensitive and one relatively resistant cell population.

Topics: Adult; Concanavalin A; Dose-Response Relationship, Radiation; Female; Hodgkin Disease; Humans; Immunosuppression Therapy; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Mitogens; Phytohemagglutinins; Radiation Tolerance

Topics: Adult; Aged; Aging; Antilymphocyte Serum; Concanavalin A; DNA; Dose-Response Relationship, Immunologic; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphopenia; Middle Aged; Time Factors

The number of lymphocytes with mobile receptors for concanavalin A (Con A) on their surface membrane (forming visible caps after the addition of fluorescein-conjugated Con A) was determined in the peripheral blood of 53 patients with Hodgkin disease. Of 29 individuals studied prior to treatment, the level of capped cells was found to be below the normal range in 9 of 13 in stages I and IIA, 6 of 8 in stage IIIA, and all 8 in stages IIIB and IV. Even among patients in remission 2 yr after successful treatment the level was below the lower normal limit in 9 of 16. The number was also reduced in 7 of 8 individuals with recurrent lymphoma. The level of lymphocytes that cap with Con A may prove to be a more sensitive measure of active Hodgkin disease than the total peripheral lymphocyte count or the level of T cells. This lymphocyte parameter merits further study as a correlate in vitro of cellular immunity.

Topics: Binding Sites; Concanavalin A; Hodgkin Disease; Humans; Leukocyte Count; Lymphocytes; T-Lymphocytes

27 consanguineous and non-consanguineous relatives to 12 patients with Hodgkin's disease (HD) have been studied. The lymphocyte DNA synthesis induced by concanavalin (ConA) was depressed in 6 patients. 7 out of 15 tested relatives (3 first degree relatives and 4 spouses) showed a profound impairment in lymphocyte response to ConA stimulation. None out of 12 relatives to ConA normal patients was defect in this respect. In relatives to ConA hyporesponsive patients there was a small but statistically significant decrease in lymphocyte response to pokeweed mitogen (PWM) and PPD in vitro. No differences in lymphocyte subpopulations were seen. The findings strongly support an exogenous factory (probably a virus) causing the depressed mitogen response in relatives to immunodeficient patients with HD. A possible linkage between the immunodeficiency and the pathogenesis of HD is discussed.

Topics: Adult; Aged; Concanavalin A; DNA; Female; Hodgkin Disease; Humans; Lymphocyte Activation; Male; Middle Aged; Mitogens; Tuberculin

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or decreased from Hodgkin's disease. Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8). All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.

Topics: Adolescent; Adult; Aged; Concanavalin A; DNA; Female; Follow-Up Studies; Hodgkin Disease; Humans; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitogens; Prognosis; Recurrence; Remission, Spontaneous

Peripheral blood lymphocytes and their in vitro reactivity have been recorded prior to treatment in 18 patients with Hodgkins disease, 11 with lymposarcoma, 13 with reticulosarcoma, 20 with various solid tumors and 37 normal control persons. The mean total numbers of lymphocytes, those of T lymphocytes,and the mean reactivity to PHA and ConA were reduced in all groups except lymphosarcoma, although with varying degrees of statistical significance. The percentages of T and B lymphocytes appeared to be normal in all groups, but the ranges of values were somewhat greater than among the normal controls. The mean total numbers of B lymphocytes were normal in all patient groups. All reductions seemed to be more pronounced in patients with disseminated than in those with localized disease, but none of these differences was statistically significant. All patient groups appeared to have reduced reactivity in MLC, while the ability to stimulate control lymphocytes was nearly normal. The results fail to indicate an in vitro immunological abberation specific to Hodgkin's disease. It seems that human malignant, neoplastic diseases are associated with a relatively selective reduction of the total numbers and reactivity of blood T lymphocytes. Various explanations of the reactivity impairment are proposed. The pathogenesis of the reduction of the total number of blood T lymphocytes remains obscure.

Topics: Adult; Aged; B-Lymphocytes; Concanavalin A; Female; Hodgkin Disease; Humans; Immune Adherence Reaction; Immunity, Cellular; Immunoglobulins; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitogens; T-Lymphocytes

Blood lymphocytes from 9 patients with Hodgkin's disease (HD) were studied. The results were compared with those of 6 seminoma testis patients and 9 healthy unrelated controls. All patients were in complete and unmaintained remission more than 10 years after termination of radiotherapy. The mean T-lymphocyte count of HD patients was lower than that of controls and seminoma testis patients. Lymphocyte DNA synthesis induced by pokeweed mitogen and phytohaemagglutinin was normal in both patient groups. Concanavalin A-induced DNA synthesis was low in 4 patients with HD although the mean stimulation of the group did not differ from controls or seminoma testis patients. Lymphocyte activation by PPD was slightly decreased in the 2 patient groups. No increase in spontaneous lymphocyte DNA synthesis was observed. The responding and stimulatory capacity in mixed lymphocyte culture was decreased in 3 and 2 HD patients respectively. 4 out of the 9 patients with HD but none with seminoma testis displayed severe impairment in T-lymphocyte functions. As 1 of the 4 had been treated solely by surgery, late effects of irradiation can only partly explain the results. The results may favour a hypothesis postulating a constitutional defect contributing to the immunoincompetence in HD.

Topics: Adolescent; Adult; Child; Concanavalin A; DNA; Dysgerminoma; Female; Hodgkin Disease; Humans; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Mitogens; Prognosis; Remission, Spontaneous; Testicular Neoplasms

The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.

Topics: Adult; Aged; Carcinoma, Bronchogenic; Cells, Cultured; Concanavalin A; Hodgkin Disease; Humans; Immune Adherence Reaction; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocyte Transfusion; Lymphocytes; Lymphoma, Non-Hodgkin; Middle Aged; Mitogens; Multiple Myeloma; Neoplasm Proteins; Neoplasms; T-Lymphocytes

Topics: B-Lymphocytes; Complement C3; Concanavalin A; Hodgkin Disease; Humans; Lectins; Lymphocyte Activation; Lymphocytes; Receptors, Antigen, B-Cell; Rosette Formation; Spleen; T-Lymphocytes

Twenty consecutive patients with Hodgkin disease in continuous complete remission and off treatment for at least 5 yr (range 5-25 yr, median 9 yr) were studied with a battery of immunologic parameters. Skin test reactivity to four common antigens, sensitization to 2,4-dinitrochlorobenzene, absolute lymphocyte count, relative percentage of T cells (as measured by spontaneous rosette formation with sheep erythrocytes) and B cells (as measured by immunofluorescence with polyvalent antiserum), and absolute number of T and B cells were normal when compared with controls. However, the mean value of lymphocyte response in vitro to the mitogen phytohemagglutinin for the study population was significantly decreased (p less than 0.001) when compared with the controls. This abnormality in response to mitogen could not be correlated with age, sex, stage, symptoms, histologic subclassification, or previous treatment. The data suggest the existence of a persisting cell-mediated immune defect in the circulating lymphocytes in patients with long-standing Hodgkin disease that might otherwise be considered "cured."

Topics: Antigens; B-Lymphocytes; Concanavalin A; Dinitrobenzenes; Female; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Immunologic Techniques; Lectins; Leukocyte Count; Lymphocyte Activation; Male; Remission, Spontaneous; Skin Tests; T-Lymphocytes

Topics: Agglutination Tests; B-Lymphocytes; Burkitt Lymphoma; Cell Membrane; Concanavalin A; Hodgkin Disease; Humans; Leukemia, Lymphoid; Lymph Nodes; Lymphocytes; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Receptors, Concanavalin A; Remission, Spontaneous; Spleen

We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.

Topics: Aged; Concanavalin A; Diseases in Twins; DNA; Female; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitogens; Pregnancy; Skin Tests; Twins, Dizygotic; Twins, Monozygotic

Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 mo after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1-10 yr after completion of treatment there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88% (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. This data suggests that there is a sustained alteration in both the number and function of circulating T cells after radiation therapy in patients with Hodgkin's disease which may persist for as long as 10 yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions. The implications of these findings with respect to the state of immunological competence after radiotherapy are discussed.

Topics: B-Lymphocytes; Concanavalin A; Dinitrochlorobenzene; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Lectins; Leukocyte Count; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphopenia; Receptors, Antigen, B-Cell; T-Lymphocytes; Tetanus Toxoid; Time Factors

1. In Hodgkin's disease patient's immunological in vitro and in vivo parameters are of prognostic importance. 2. Skin test reactivity correlates to peripheral T-lymphocyte counts and Con A induced lymphoblastogenesis. 3. Con A is the most sensitive in vitro indicator for detecting latent immunodeficiency. 4. Hodgkin patients in long term remission after tumor reductive therapy exhibit a qualitative and quantitative lymphocyte defect. 5. In Hodgkin patients Herpes virus related antibody titers are elevated against Epstein Barr virus (EBV). The elevation coincides with a decreased T-cell number and function. Antibodies against other Herpes viruses (HSV, CMV, VZV) are in the normal range, when tested by the complement fixation method.

Topics: Antibodies, Viral; Concanavalin A; Herpesvirus 4, Human; Hodgkin Disease; Humans; Lymphocyte Activation; Prognosis; Remission, Spontaneous; Skin Tests; T-Lymphocytes

The treatment of a case of Hodgkin's disease (lymphocyte predominance, stage IV B) with exogenous i.m. interferon therapy is described. B symptoms disappeared, diseased nodes and pulmonary infiltrations decreased in size, and laboratory values normalized. Clinical improvement was associated with increased mitogenic responsiveness of the patient's lymphocytes towards various stimuli in vitro. After almost half a year's treatment tumour progression and a decreased mitogenic response were again observed. Interferon treatment was then abandoned and combined cytostatic courses were instituted. Partial remission was achieved after 6 months of cytostatic therapy, i.e. 1 year after the start of treatment.

Topics: Adult; Antineoplastic Agents; Concanavalin A; Drug Therapy, Combination; Hodgkin Disease; Humans; Interferons; Lectins; Lymphocyte Activation; Male; Mitogens

The effect of thymosin on in vitro reactivity of peripheral lymphocytes to phytohemagglutinin, concanavalin A, and the formation of spontaneous E-rosettes in 54 patients with metastatic carcinomas has been studied. Thymosin increased lymphocyte responses to PHA and Con A in only 10 patients, with predominant effect seen with Con A. Twenty patients showed depressed baseline levels of E-rosettes which were increased to normal or subnormal levels after incubation with thymosin. No distinct correlation was noted between the clinical stage of the disease and the ability of lymphocytes to form E-rosettes. Although the exact mechanism by which the thymus exerts its influence on host resistance is not clearly defined, present evidence supports the concept that the thymic hormone, thymosin, may be an important addition in treatment of cancer patients by increasing cell-mediated immunity.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Carcinoma, Bronchogenic; Concanavalin A; Hodgkin Disease; Humans; Immune Adherence Reaction; In Vitro Techniques; Lectins; Middle Aged; Neoplasms; T-Lymphocytes; Thymosin; Thymus Extracts

In vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A- and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA.

Topics: Adolescent; Adult; Child; Concanavalin A; Female; Hodgkin Disease; Humans; Lectins; Lymphocyte Activation; Lymphokines; Male; Middle Aged; Skin Tests; Splenectomy

Topics: Antigens, Neoplasm; Antigens, Viral; Binding Sites, Antibody; Cell Line; Concanavalin A; Herpesvirus 4, Human; Hodgkin Disease; Humans; Lymphatic Diseases; Lymphoma

Concanavalin A (Con A) induces movement of its receptors on the cell surface membrane. This induction results in a concentration of Con A site complexes on one pole of the cell to form a cap. A marked difference was found in the mobility of Con A receptor between lymphocytes from normal persons and lymphocytes from patients with Hodgkin's disease and other malignant lymphomas. Lymphocytes isolated from tonsils of patients undergoing tonsillectomy and from axillary lymph nodes of breast cancer patients exhibited approximately 30% of cells with caps, which is identical with the cap formation ability of normal lymphocytes. In biopsy material from patients with Hodgkin's disease and other malignant lymphomas, a significant decrease in the ability of the lymphocytes to form caps was observed. This difference in the mobility of Con A sites was even more pronounced in lymphocytes isolated from the peripheral blood. In 123 patients with Hodgkin's disease and other malignant lymphomas, cap formation ranged between 3 and 12%. The ability of cells, from a normal donor or a lymphoma patient, to form caps was independent of the source from which the lymphocytes were isolated, e.g., lymph node, spleen, or blood. Lymphocytes from patients with lymphoma were also agglutinated by Con A to a higher degree than normal lymphocytes. These findings are discussed in relation to the association of the lymphocytes with these malignancies and as a possible aid in their differential diagnosis.

Topics: Agglutination; Binding Sites, Antibody; Cell Membrane; Concanavalin A; Hodgkin Disease; Humans; Lymph Nodes; Lymphocytes; Lymphoma; Lymphoma, Non-Hodgkin; Palatine Tonsil

Lymphocytes were isolated from the peripheral blood of 21 normal persons and 66 patients with chronic lymphocytic leukemia (CLL), CLL in remission, Hodgkin's disease, Hodgkin's disease in remission, various other tumors, or cardiovascular diseases; The lymphocytes were studied for cap formation and agglutinability by concanavalin A, and for cell attachment to the surface of a petri dish. The frequency of cap formation was lowest in lymphocytes from patients with untreated Hodgkin's disease (2.1 plus or minus 0.8%), next lowest in lymphocytes from patients with CLL who were or were not under treatment (7,0 plus or minus 1;3%), and also low in Hodgkin's disease in remission (10.6 plus or minus 1.2%). The frequencies of cap formation by lymphocytes from patients with various other tumors (19.1 plus or minus 2.5%), with CLL in remission (24.0 plus or minus 0.9%), and with nonmalignant diseases (26.0 plus or minus 2.2%) were more similar to the frequency found in lymphocytes from normal persons (29.4 plus or minus 2.8%). Lymphocytes from all the patients, including those in remission, showed a higher degree of agglutinability by concanavalin A than lymphocytes from normal persons. Cell attachment to a petri dish was highest with CLL, next highest with CLL in remission, and low for normal persons and all the other patients. Lymphocytes from normal persons that consisted predominantly of thymus-derived cells gave similar results to isolated normal bone marrow-derived cells. The results indicate that there were different changes in the surface membrane of lymphocytes from patients with CLL, CLL in remission, Hodgkin's disease, and Hodgkin's disease in remission, and that the patients in clinical remission still showed abnormalities in their lymphocytes.

Topics: Adolescent; Adult; Aged; Agglutination; Cell Adhesion; Cell Membrane; Concanavalin A; Female; Hodgkin Disease; Humans; Leukemia, Lymphoid; Lymphocytes; Male; Middle Aged; Neoplasms; Remission, Spontaneous

Blood lymphocytes from the majority of 33 unselected and untreated patients with Hodgkin's disease were deficient in T-lymphocytes and their DNA synthesis induced by concanvallin A mitogen and PPD antigen was impaired. The spontaneous DNA synthesis during the first 24 hours of culture was often raised. The prognostic role of the lymphocyte deficiency was evaluated in a follow-up 10-22 months after institution of therapy. The lymphocyte functions were more commonly abnormal in patients responding poorly to treatment (incomplete remission, relapse after treatment, or death) than in patients entering complete remission. The lymphocyte deficiency seems to give information about prognosis in Hodgkin's disease in addition to histopathology, clinical stage, B-symptoms and age.

Topics: Adult; Age Factors; Aged; Concanavalin A; DNA, Neoplasm; Follow-Up Studies; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Middle Aged; Prognosis; T-Lymphocytes; Tuberculin

A standardized microculture system has been developed to assess the ability of lymphocytes to secrete leukocyte migration inhibitory factor (LMIF) in response to the nonspecific mitogen concanavalin(Con A). LMIF-rich supernates collected from stimulated lymphocytes cultured in plastic microtiter plates are assayed by pulse exposure of purified human granulocytes and inhibition of their migration in agarose medium. LMIF activity in this system is suppressed by the protein synthesis inhibitor puromycin, but not by inhibition of lymphocyte proliferation by irradiation. It is demonstrated that normal lymphocytes stimulated with mitogen elaborate LMIF activity, while lymphocytes from malignant lymphoma patients are frequently unable to produce it. Thus, mitogen-induced mediator production may be a useful parameter in further characterization of primary and secondary immunodeficiencies.

Topics: Cell Migration Inhibition; Concanavalin A; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphocytes; Macrophage Migration-Inhibitory Factors; Puromycin

Topics: Aged; Agglutination Tests; Cell Membrane; Concanavalin A; Female; Hodgkin Disease; Humans; Immune Adherence Reaction; Immunity, Cellular; Leukemia, Lymphoid; Lymphocytes; Male; Middle Aged; Remission, Spontaneous; Stimulation, Chemical; Vinblastine

Topics: Binding Sites; Bone Marrow; Bone Marrow Cells; Concanavalin A; Fluoresceins; Hodgkin Disease; Humans; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Microscopy, Fluorescence; Receptors, Drug

Topics: Animals; Antilymphocyte Serum; Azathioprine; B-Lymphocytes; Bacterial Infections; Concanavalin A; Dermatitis, Atopic; Graft Rejection; Hodgkin Disease; Humans; Immunosuppressive Agents; Kidney Transplantation; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Prednisone; Rabbits; Renal Dialysis; Sarcoidosis; T-Lymphocytes; Transplantation, Homologous

Topics: Cell Transformation, Neoplastic; Concanavalin A; Hodgkin Disease; Humans; Immune Adherence Reaction; Immunity, Cellular; Lectins; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Mitogens; T-Lymphocytes

Topics: Animals; Cells, Cultured; Complement System Proteins; Concanavalin A; DNA; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Immunoglobulins; Kidney Diseases; Lectins; Leukemia, Lymphoid; Rabbits; T-Lymphocytes; Tritium