concanavalin-a and Agammaglobulinemia

Topics: Agammaglobulinemia; alpha-Fetoproteins; Antibodies; Antibody Formation; Autoimmune Diseases; B-Lymphocytes; Concanavalin A; DNA; Epitopes; Genes, MHC Class II; Growth Inhibitors; Hybrid Cells; Hypersensitivity; Immune Tolerance; Immunity, Cellular; Immunoglobulins; Immunotherapy; Interferons; Lymphocyte Culture Test, Mixed; Multiple Myeloma; Nucleotides, Cyclic; Prostaglandins; T-Lymphocytes; T-Lymphocytes, Regulatory; Terminology as Topic; Thymus Hormones

Topics: Agammaglobulinemia; Animals; B-Lymphocytes; Cells, Cultured; Concanavalin A; DNA; Fetal Blood; Hemolytic Plaque Technique; Herpesvirus 4, Human; Humans; Immune Sera; Immunoglobulin G; Immunoglobulin M; Infectious Mononucleosis; Leukemia, Lymphoid; Lymphocyte Activation; Pokeweed Mitogens; T-Lymphocytes

Topics: Acrylamides; Adolescent; Adult; Agammaglobulinemia; Age Factors; Antibody Formation; Arthritis, Rheumatoid; B-Lymphocytes; Concanavalin A; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphocyte Activation; Male; Middle Aged; Nitrobenzenes; Receptors, Antigen, B-Cell; T-Lymphocytes; Trinitrobenzenes

Topics: Agammaglobulinemia; Animals; Antigens; Autoimmune Diseases; Binding, Competitive; Cell Transformation, Neoplastic; Chickens; Concanavalin A; Dysgammaglobulinemia; Epitopes; Genes; Humans; Immune Tolerance; Immunity, Cellular; Immunoglobulin A; Immunoglobulin Allotypes; Immunoglobulin E; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lymphokines; Mice; Mycoses; Rabbits; T-Lymphocytes

Topics: Agammaglobulinemia; Animals; Antibody Formation; Antibody Specificity; Antigens; Antilymphocyte Serum; Autoimmune Diseases; Binding, Competitive; Cell Separation; Concanavalin A; Epitopes; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Memory; Immunosuppression Therapy; Lymphocyte Culture Test, Mixed; Lymphokines; Mice; Spleen; T-Lymphocytes; Thymectomy

Acute non-A, non-B hepatitis developed in twelve patients with primary hypogammaglobulinaemia during treatment with intravenous gammaglobulin prepared by Cohn fractionation of pooled plasma. The illness was clinically and histologically identical to the short-incubation non-A, non-B, hepatitis observed in haemophilic patients receiving factor VIII concentrates. Most of the patients were symptomless, but 10 months after onset ten of the twelve still had abnormal liver function. The occurrence of non-A, non-B hepatitis in agammaglobulinaemics indicates that humoral mechanisms are not essential for production of hepatocyte necrosis in this infection. This outbreak emphasises the need for a screening test to identify the agent in blood products, and shows that Cohn fractionation of plasma does not always inactivate the agent. Furthermore, the finding that the virus can be transmitted in IgG concentrates suggests either that the general population has a very low level of antibodies to the putative virus or that such antibodies are not virus-neutralising.

Topics: Agammaglobulinemia; Aspartate Aminotransferases; Clinical Trials as Topic; Concanavalin A; Female; Hepatitis C; Hepatitis, Viral, Human; Humans; Immunoglobulins; Injections, Intramuscular; Injections, Intravenous; Phenotype; T-Lymphocytes

Recurrent bacterial infections due to humoral immunodeficiency are an important cause of death in myeloma patients. Recent data indicate that CD8+ T lymphocytes and a reduction of T helper type 1 cells with disease progression may be involved in the regulation of polyclonal immunoglobulin secretion. In mixed lymphocyte cultures derived from peripheral blood mononuclear cells (PBMC) of 24 myeloma patients with reduced immunoglobulin serum levels we investigated the association of CD4+ and CD8+ T cell subsets and immunoglobulin-secreting B cells (ISC) upon mitogenic stimulation with pokeweed mitogen (PWM) and concanavalin A (Con A). In supernatants of cultured PBMC of myeloma patients the spontaneous secretion of the type 1 cytokine interferon-gamma was reduced. After PWM stimulation reduced numbers of polyclonal ISC were found in 79% of patients, and monoclonal ISC were observed in 12% of patients. After Con A stimulation, again formation of polyclonal ISC was reduced, but monoclonal ISC were found in 41% of patients. Elevation of monoclonal and reduction of polyclonal ISC after stimulation with Con A were associated with an increase of CD8+ CD11b+ Leu-8- T cells (P<0.05). We conclude that the elevated numbers of CD8+ CD11b+ Leu-8- T cells play a role in the stimulation of monoclonal and suppression of polyclonal immunoglobulin secretion in myeloma patients.

Topics: Agammaglobulinemia; Aged; B-Lymphocytes; CD8-Positive T-Lymphocytes; Concanavalin A; Female; Humans; Immunoglobulins; Interferon-gamma; Interleukin-6; L-Selectin; Lymphocyte Activation; Macrophage-1 Antigen; Male; Middle Aged; Multiple Myeloma; Pokeweed Mitogens

The maturation of normal B lymphocytes proceeds through a growth phase and a differentiation phase. These two phases appear to be under the influence of mediators released by immune cells, B-cell growth factor(s), which induce proliferation of B cells; and B-cell differentiation factor(s), which induce B-cell differentiation.. We analyzed the ability of peripheral blood mononuclear cells from patients with hypogammaglobulinemia to produce B-cell growth factor and B-cell differentiation factor activity in comparison with normal peripheral blood mononuclear cells.. Of 27 patients tested, 26 had normal production of B-cell growth factor activity. A quantitative but not absolute defect in B-cell growth factor production was demonstrable in one boy with hypogammaglobulinemia. Interleukin-2 and interleukin-4 levels, as determined antigenically in these supernatants, had a similar distribution pattern from patients' or from control peripheral blood mononuclear cells; that is, undetectable levels of interleukin-2 were produced by cells from 4 of 16 patients tested and from 4 of 13 control subjects, and undetectable levels of interleukin-4 produced by cells from 6 of 16 patients and 4 of 13 control subjects. B-cell differentiation factor activity was absent in only one child tested but present in all other patients. Two patients had quantitatively low secretion of B-cell differentiation factor, but all others were within normal range. The two patients with quantitatively depressed B-cell differentiation factor activity had normal levels of B-cell growth factor activity, interleukin-2, and interleukin-4 produced from their cells.. Peripheral blood mononuclear cells from the majority of patients with hypogammaglobulinemia appear to have the capacity to produce B-cell growth factors and B-cell differentiation factor activity in vitro.

Topics: Adolescent; Adult; Agammaglobulinemia; B-Lymphocytes; Cell Differentiation; Cell Division; Child; Child, Preschool; Concanavalin A; Growth Substances; Humans; Interleukin-2; Interleukin-4; Interleukin-6; Male; Middle Aged; Monocytes; Reference Values

We report six Chinese boys with hypogammaglobulinaemia. All but one had very low or undetectable circulating B-lymphocytes, two had reversed CD4/CD8 ratios (in one of whom this latter became normal), one had reduced lymphocyte proliferative responses to concanavalin A and pokeweed mitogen and three had deficient responses to OKT3. Generation of antibody-secreting cells in response to pokeweed mitogen was markedly defective in all patients. Co-cultures of purified lymphocyte subsets from the patients with those of normal donors revealed that in addition to B-cell deficiency seen in all patients, two had T-helper cell deficiency and two had T-suppressor cell hyperactivity. One of the latter patients was treated with cimetidine in an attempt to ablate histamine type 2 receptor-bearing suppressor cells: the absolute number of such cells was temporarily reduced but there was no concurrent correction of the functional hyperactivity. These studies point to the variable nature of T-regulatory cell deficiencies in hypogammaglobulinaemia.

Topics: Adolescent; Agammaglobulinemia; B-Lymphocytes; CD4-CD8 Ratio; Child; Child, Preschool; China; Concanavalin A; Humans; Infant; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Muromonab-CD3; Pokeweed Mitogens; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The phenotypes of two different types of suppressor T cells in the chicken, both capable of inhibiting secondary antibody responses in vitro, were determined. The first of these, induced by injection of concanavalin A (Con A) into normal chickens, was CT8+, TcR2+ (alpha beta), CT4-, TcR1- (gamma delta). These cells appeared to exhibit histamine type 2 (H2) receptors, as they adhered to cimetidine-BSA-coated dishes. Moreover, cimetidine added to the medium at 2 x 10(-4) M completely prevented the suppression induced by these suppressor cells. The second type of 'suppressor' T-cell studied, induced in agammaglobulinaemic (A gamma) chickens by injection of bursa cells, exhibited the same phenotype, but was insensitive to cimetidine and did not adhere to cimetidine-BSA-coated dishes, indicating heterogeneity with respect to H2 receptor expression on CT8+ chicken T cells with suppressor activity. The results also showed that a relatively larger proportion of CT8+ than of CT4+ cells adhered to cimetidine-BSA-coated dishes and thus appeared to be H2 receptor positive. TcR1 (gamma delta) cells did not contribute significantly to the antigen non-specific suppressor effects examined in this study.

Topics: Agammaglobulinemia; Animals; Antibody-Producing Cells; Antigens, Differentiation, T-Lymphocyte; Bursa of Fabricius; Chickens; Cimetidine; Concanavalin A; Hemolytic Plaque Technique; Immunologic Memory; Receptors, Histamine H2; Serum Albumin, Bovine; Spleen; T-Lymphocytes, Regulatory

The effects of cyclosporin A (CsA) treatment and hormonal bursectomy on Eimeria tenella infection of chickens were investigated to evaluate the role of humoral antibody and cell-mediated immunity (CMI) in the host protective immunity to an intestinal protozoan disease, coccidiosis. Hormonal bursectomy had no significant effect on the host response to E. tenella. CsA treatment had a differential effect on the course of disease depending on how CsA was given relative to infection. Daily administration of CsA for 7 days beginning 1 day before primary infection with E. tenella enhanced disease resistance, whereas a single dose of CsA given before primary infection enhanced disease susceptibility compared with that of untreated controls. Chickens treated with CsA during the primary infection were resistant to reinfection at 5 weeks post-primary infection. Treatment of chickens immune to E. tenella with CsA at the time of secondary infection abrogated their resistance to reinfection despite the presence of high levels of coccidia-specific secretory immunoglobulin A and serum immunoglobulin G. Splenic lymphocytes obtained after CsA treatment demonstrated a substantially depressed concanavalin A response, but not a depressed lipopolysaccharide response. Because CsA was not directly toxic to parasites in vivo when administered during the secondary infection, these results suggest that CsA interacts with the immune system to allow priming during the primary infection, while interfering with the effector function of CMI during the secondary infection. Taken together, present findings indicate that CMI plays a major role in host protective immunity to E. tenella.

Topics: Agammaglobulinemia; Animals; Antibody Formation; B-Lymphocytes; Bursa of Fabricius; Chickens; Coccidiosis; Concanavalin A; Cyclosporins; Eimeria; Immunosuppression Therapy; Lipopolysaccharides; Lymphocyte Activation

In co-cultures with control cells lymphocytes obtained from some patients with hypogammaglobulinaemia can suppress PWM but not S. aureus Cowan I-induced polyclonal immunoglobulin production. When such co-cultures were stimulated at the same time with both mitogens, the response was greatly suppressed. This phenomenon was further studied in cultures of lymphocyte populations isolated from healthy donors. It was found that suppressor T lymphocytes activated by PWM in cultures co-stimulated with Con A, with high T:B cell ratio, or with an increased proportion of OKT8+ T cells can suppress the S. aureus-induced response. In contrast, under the same conditions S. aureus did not activate suppressor cells. Moreover, in cultures stimulated with this polyclonal B-cell activator OKT8+ lymphocytes could serve as helper cells.

Topics: Agammaglobulinemia; Antibodies, Bacterial; Antigens, Bacterial; Cells, Cultured; Concanavalin A; Humans; Immune Tolerance; Lymphocyte Activation; Pokeweed Mitogens; Staphylococcus aureus; T-Lymphocytes, Regulatory

Topics: Agammaglobulinemia; Child, Preschool; Concanavalin A; Female; Humans; Immunoglobulin G; T-Lymphocytes; T-Lymphocytes, Regulatory

In the course of an analysis of lymphocyte functions of common variable immunodeficiency patients, we found one patient whose T lymphocytes released B cell differentiation factor (BCDF) and B cell growth factor (BCGF) without IL 2 production upon stimulation with Con A. The patient was a 68-yr-old woman with hypo-gamma-globulinemia (IgM: 31 mg/dl, IgG: 223 mg/dl, IgA: 23 mg/dl); she suffered from cryptococcal meningitis and pulmonary tuberculosis with a negative result of skin tests to PPD and cryptococcal antigen. The number of T cells and the ratio of T cell subsets (Leu-2a and Leu-3a) was normal. T cells showed no proliferative response to Con A and a low response to PHA (one-tenth of normal response). The addition of patient T cells to normal T cells did not inhibit the proliferation of normal T cells when stimulated by Con A. The culture supernatant of Con A-stimulated T cells contained no IL 2 activity when assayed by an IL 2-dependent T cell line. Expression of Tac antigen was not impaired by Con A stimulation and the addition of partially purified IL 2 from the supernatant of Jurkat T cell line-induced proliferation of Con A-stimulated T cells, indicating that the defect observed was not in IL 2-responding cells but in IL 2-producing cells. In contrast, the culture supernatant of the T cells stimulated by Con A or PHA contained BCDF activity as much as that of normal T cells when assayed by Cowan I-stimulated normal B cells or the B lymphoblastoid cell line SKW6-CL4. The supernatant also contained BCGF activity. These results suggest that B cell-stimulating factor (BCGF, BCDF) and IL 2 may be synthesized by different subsets of T cells or that the synthesis of those lymphokines are independently regulated in the same cells.

Topics: Adult; Agammaglobulinemia; Aged; Antigens, Surface; B-Lymphocytes; Concanavalin A; Female; Growth Substances; Humans; Interleukin-2; Interleukin-4; Lymphocyte Activation; Lymphokines; Phytohemagglutinins; T-Lymphocytes; Tumor Necrosis Factor Receptor Superfamily, Member 7

Antigen-specific antibody responses were investigated in 32 hypogammaglobulinemic patients with common variable immunodeficiency following in vitro sensitization of their peripheral blood lymphocyte cultures with sheep red blood-cell determinants. Anti-sheep red blood-cell antibody-secreting cells were quantitated in a hemolytic plaque assay. Amplification of T-cell help was achieved with the use of the T-cell mitogen concanavalin A or allogeneic irradiated T cells. Four patients groups, A through D, were identified. Group A was comprised of 10 patients whose cultured lymphocyte readily developed into antibody secreting cells. Cultures of 9 patients (Group B) responded suboptimally, but were enhanced following mitogen activation of autologous or exogenous T cells, and those of 7 patients (Group C) responded only when help was amplified. In 7 patients (Group D), no responses were elicited. On the simultaneous assessment of pokeweed mitogen-driven polyclonal generation of immunoglobulin-secreting cells, only 10 responders, all from groups A and B, were identified. Our observations indicate that the majority of patients with common variable immunodeficiency possesses B cells capable of producing antibody in vitro. The ability of some patients' B cells to respond only in the antigen-specific assay while failing to do so in pokeweed mitogen-stimulated cultures suggests that these two reactions are not identical in their activation pathways.

Topics: Adolescent; Adult; Agammaglobulinemia; Animals; Antibody-Producing Cells; B-Lymphocytes; Child; Child, Preschool; Concanavalin A; Epitopes; Erythrocytes; Female; Hemolytic Plaque Technique; Humans; Infant; Male; Middle Aged; Pokeweed Mitogens; Sheep; T-Lymphocytes; T-Lymphocytes, Regulatory

We investigated the immune function of a patient with anergy and acquired hypogammaglobulinemia. Despite normal numbers of B cells and T4+ inducer and T5+ suppressor T cells, this patient's lymphocytes did not produce immunoglobulin, proliferate in response to soluble antigens, or generate helper factors in vitro. In addition, her T4+ T cells did not express la molecules after stimulation by soluble antigen. In mixing experiments, her T cells did not induce immunoglobulin secretion by B cells from a normal, HLA-D-identical sibling; this failure was not due to excessive suppression, since the patient's T cells did not abrogate immunoglobulin production by the normal sibling's T and B cells. Moreover, the patient's B cells secreted immunoglobulin in the presence of the sibling's T4+ cells. In contrast to the deficient inducer cells, the patient's T5+ T cells were capable of expressing suppressor-cell functions. These results indicate that immunodeficiency may occur because of a selective loss of T4+ inducer function.

Topics: Agammaglobulinemia; Antibody Formation; Child; Concanavalin A; Female; Histocompatibility Antigens Class II; Humans; Immunologic Deficiency Syndromes; Isoantigens; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; T-Lymphocytes

Mononuclear cells from 39 patients with hypogammaglobulinemia of the common variable type were analyzed for in vitro proliferative response to a panel of cell activators in order to examine the lymphocyte response to mitogens and to study the capacity to generate an immunologically specific secondary response. Patient lymphocyte response to phytohemagglutinin and concanavalin A was found to be significantly lower than that of controls studied in parallel (P less than 0.01), and low response did not correlate with T-lymphocyte number. Response to pokeweed mitogen was significantly lower than that of controls (P less than 0.01), but response to zinc, tested in a few patients, was normal. Strong depressions of patient lymphocyte proliferative responses to Candida albicans, Escherichia coli, and Staphylococcus aureus were observed (P less than 0.01); all of these microbial activators require intact B-cell function for maximum response. Repeated testing of individual patients indicated that poor lymphocyte response could be consistently observed. Examination of change in vitro lymphocyte response during clinical course and disease management showed that a consistent pattern of intrinsic lymphocyte functional deficiency could be demonstrated.

Topics: Adolescent; Adult; Agammaglobulinemia; Aged; Candida albicans; Child; Child, Preschool; Concanavalin A; Female; Humans; IgA Deficiency; IgG Deficiency; Immunity, Cellular; Immunoglobulin M; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Rosette Formation; Zinc

Normal levels of lymphocyte cyclic AMP were found in fourteen of fifteen patients with primary hypogammaglobulinaemia. One patient with adult-onset hypogammaglobulinaemia had low cyclic AMP levels with a very poor rise after prostaglandin E1 stimulation. Five of the patients had severely depressed thymidine uptake by their phytohaemagglutinin-stimulated lymphocytes but there was no significant difference between their lymphocyte cyclic AMP levels and those of patients with normal lymphocyte responses. Removal of monocytes from concanavalin A-stimulated lymphocyte cultures from three of these patients did not affect the severe depression of leucine uptake. These findings indicate that the depression of lymphocyte response to mitogens seen in some patients with late-onset primary hypogammaglobulinaemia is not due to raised levels of lymphocyte cyclic AMP; and not usually due to prostaglandins released by monocytes in the cultures.

Topics: Adult; Agammaglobulinemia; Concanavalin A; Cyclic AMP; Humans; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; Prostaglandins E; Thymidine

Topics: Agammaglobulinemia; Aging; Animals; Antigens, Surface; B-Lymphocytes; Bursa of Fabricius; Chickens; Concanavalin A; Female; Guinea Pigs; Immunization; Immunization, Passive; Immunoglobulin M; Major Histocompatibility Complex; Male; Rabbits; Spleen; T-Lymphocytes, Regulatory

A case of acquired hypogammaglobulinaemia has been examined. Total and differential leucocyte counts and distribution were normal as were the lymphocyte sub-populations when defined by surface membrane immunoglobulin, E-, EA- and EAC-rosette techniques. The proliferative response of unseparated lymphocytes to PHA and Con-A was normal while the response to PWM was clearly impaired. In contrast, testing of purified B-lymphocytes by PWM was within the normal range. The response to PWM was found to be depressed by adding the patient's T-lymphocytes to autologous B-lymphocytes as well as to B-lymphocytes from 10 normal, healthy controls. The patient's T-lymphocytes were further tested for cytotoxicity against autologous. B-lymphocytes and B-lymphocytes from the 10 control individuals. Cytotoxicity was observed against autologous B-lymphocytes and against the B-lymphocytes of 3 controls. These findings indicate the presence of peripherally circulating unspecific T-suppressor lymphocytes and cytotoxic T-lymphocytes of some immunogenetic specificity. The suppressor and cytotoxic T-lymphocytes may separately or in combination be involved in the pathogenesis of hypogammaglobulinaemia. Thus, these findings are equivocal but underline the immunologic aspects of the pathogenesis.

Topics: Agammaglobulinemia; B-Lymphocytes; Concanavalin A; Cytotoxicity, Immunologic; Female; Humans; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; T-Lymphocytes, Regulatory

Topics: Agammaglobulinemia; Animals; Autoimmune Diseases; Chickens; Concanavalin A; Humans; Immunologic Deficiency Syndromes; Lymphocyte Cooperation; Macrophages; Mice; Mycoses; Neoplasms; Prostaglandins; T-Lymphocytes; T-Lymphocytes, Regulatory

We present the immunological studies on 2 patients, one with the Wiskott-Aldrich syndrome and another with common variable hypogammaglobulinemia. Although these patients represent two different immunodeficiency defects, both had a subpopulation of peripheral lymphocytes which had simultaneously T and B characteristics. Their peripheral blood mononuclear cells had a low responsiveness to polyclonal mitogens. We suggest that these unusual cells represent a subpopulation of suppressor cells or of immature T cells, which may have an essential role in the pathogenesis of these immunodeficiencies.

Topics: Adult; Agammaglobulinemia; B-Lymphocytes; Concanavalin A; Female; Humans; Immunoglobulin M; Lymphocyte Activation; Lymphocytes; Male; Phytohemagglutinins; Pokeweed Mitogens; Receptors, Antigen, B-Cell; Rosette Formation; T-Lymphocytes; Wiskott-Aldrich Syndrome

We studied the interaction of lipopolysaccharide (LPS) and concanavalin A (Con A) with regard to IgM and IgG production in in vitro cultures of human peripheral blood lymphocytes (PBL). In our system LPS alone over a wide range of concentrations did not stimulate detectable IgM or IgG production, while Con A at optimal (6 microgram/ml) and suboptimal (0.6 microgram/ml) mitogenic concentrations induced synthesis of small amounts of Ig. A marked enhancing effect was present when both Con A and LPS were added to the cultures. The different doses of LPS has similar effects on both classes of Ig, and typical dose-response curves were obtained. To evaluate the cellular basis of this synergism, the effect on cell proliferation was studied under identical experimental conditions in normal subjects and patients with X-linked agammaglobulinaemia (X-LA). Parallel cultures were set up after monocyte depletion by adherence on Petri dishes. On day 3, increasing doses of LPS were associated with progressive decreases in 3H-thymidine (3H-TdR) incorporation. Similar results were obtained with normal lymphocytes and those from X-LA patients. Monocyte depletion did not substantially alter the lymphocyte response pattern. The preferential induction of helper activities, either directly by helper stimulation or indirectly by suppressor inhibition, is suggested as a possible mechanism of the interaction observed.

Topics: Agammaglobulinemia; Cell Division; Cells, Cultured; Concanavalin A; DNA; Dose-Response Relationship, Drug; Humans; Immunoglobulin G; Immunoglobulin M; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes

We studied a five-year-old girl with several autoimmune disorders and a 16-year-old boy with acquired agammaglobulinemia to determine whether aberrations of immunoregulatory T cells could explain some instances of immunodeficiency or autoimmunity. The normal peripheral blood T-cell population, as defined by specific heteroantiserums, is 20 per cent TH2+ and 80 per cent TH2-. Human suppressor cells are TH2+, whereas helper cells are TH2-. In addition, each subset expresses Ia antigens upon activation. Our patient with autoimmune disease had no demonstrable TH2+ cells, and her lymphocytes could not be induced to suppress. Her circulating T cells were of an activated-helper phenotype, i.e., TH2-,Ia+. In contrast, in the boy with agammaglobulinemia, the T-cell population was predominantly of an activated-suppressor phenotype, i.e., TH2+,Ia+. This patient's T cells abrogated both his own and his histoidentical brother's B-cell secretion of immunoglobulins. We conclude that the characterization of T cells may provide insight into the causes of a number of abnormal immune states in man.

Topics: Adolescent; Agammaglobulinemia; Autoimmune Diseases; B-Lymphocytes; Cell Separation; Child, Preschool; Concanavalin A; Female; Hemolytic Plaque Technique; Humans; Immunoglobulins; Lymphocyte Activation; Male; Mitogens; T-Lymphocytes; T-Lymphocytes, Regulatory

Human peripheral blood mononuclear cells showed increased synthesis and secretion of protein in response to stimulation by mitogens. Protein secretion in response to concanavalin A (Con A) correlated with cellular proliferation and originated from the proliferating cells. Selective depletion of either B lymphocytes or monocytes did not lead to a reduction in the total protein secreted, suggesting that the T lymphocyte was the cell contributing most of the synthetic activity. It is concluded that the measurement of newly synthesized and secreted protein by Con A activated mononuclear cells is a measurement of the T-lymphocyte response.

Topics: Agammaglobulinemia; Concanavalin A; DNA; Humans; Kinetics; Lectins; Lymphocyte Activation; Mitomycins; Proteins; T-Lymphocytes

Staphylococcus aureus protein A-positive bacteria have recently been proposed as selective B lymphocyte mitogens. We have studied the lymphocyte response to such mitogens in bacteria in normal subjects and in patients with primary immunodeficiencies. Patients with primary T cell defects show a normal response to protein A-positive bacteria and impaired responses to PHA and Con A. In contrast, patients with Bruton agammaglobulinaemia respond normally to these T cell mitogens but not to the bacteria. Thus, protein A-positive bacteria fulfil the criteria for being a T cell-independent B cell mitogen for human peripheral blood cells.

Topics: Adult; Agammaglobulinemia; B-Lymphocytes; Child; Child, Preschool; Concanavalin A; Female; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Staphylococcal Protein A; Staphylococcus aureus; T-Lymphocytes; Thymidine

A plaque assay that detects human mononuclear blood cells producing immunoglobulin (Ig)M antibody to sheep erythrocytes was investigated for its usefulness in studying B-cell activation and regulation in 24 patients with humoral immunodeficiency. Cells from 3 of 15 patients with common variable agammaglobulinemia produced some plaques (range 40--160/10(6) cells; normal range 80--1240/10(6)), but those from the other 12, from all 7 with x-linked agammaglobulinemia and from the 2 with x-linked immunodeficiency with hyper-IgM failed to produce any detectable plaques. In co-cultures of patient and normal cells a very good correlation was seen between results of the plaque assay and an IgM biosynthesis assay in detecting excessive suppressor cell activity. Cells from 7 of 15 common variable agammaglobulinemics, from 3 of 7 x-linked agammaglobulinemics, and from both patients with hyper-IgM caused significant suppression of IgM biosynthesis and(or) plaque formation by normal cells. The observations in the last two groups and discordance for excess suppressor activity in identical twins with common variable agammaglobulinemia suggest that the activity develops secondarily to whatever their primary defects may be. Culturing non-T cells from common variable agammaglobulinemics exhibiting excessive suppressor cell activity with normal T cells resulted in plaque formation in four of five patients so studied; in all five the suppressor activity was found in the T-cell population. The availability of a plaque assay for the study of blood cells from immunodeficient patients provides a new probe to examine the cellular nature of such defects.

Topics: Adolescent; Adult; Agammaglobulinemia; Antibody-Producing Cells; B-Lymphocytes; Cell Count; Child; Child, Preschool; Concanavalin A; Hemolytic Plaque Technique; Humans; Immunoglobulin M; Immunologic Deficiency Syndromes; Infant; Phytohemagglutinins; Pokeweed Mitogens; Puromycin; Rosette Formation; T-Lymphocytes

Topics: Adult; Agammaglobulinemia; B-Lymphocytes; Concanavalin A; Culture Techniques; Cytotoxicity Tests, Immunologic; Heterozygote; Humans; Immunoglobulins; Lectins; Lymphocytes; Microscopy, Electron; Mitogens; T-Lymphocytes; Time Factors

Topics: Absorption; Adult; Agammaglobulinemia; Animals; Antibody Specificity; Antigens; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Concanavalin A; Cytotoxicity Tests, Immunologic; Epitopes; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Infant; Lectins; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Rabbits; Spleen; Splenomegaly; T-Lymphocytes; Thymus Gland; Tissue Extracts

Topics: Agammaglobulinemia; Animals; B-Lymphocytes; Cell Membrane; Cell Separation; Chickens; Chromium Radioisotopes; Concanavalin A; Cytotoxicity Tests, Immunologic; Erythrocytes; Glass; Humans; Immunoglobulins; Lectins; Lymphocyte Depletion; Lymphocytes; Nylons

Cultures of chicken lymphoid tissues were tested for their capacity to lyse (51)Cr-labeled chicken, burro (BRC), and human red blood cells (HRC) in the presence of phytomitogens. PHA-stimulated cultures lysed all three types of targets, while PWM and Con A showed a "target cell specificity" for HRC and BRC, respectively. In mixtures of target cells only the appropriate targets were lysed by lymphocytes activated by either Con A or PWM indicating that soluble lymphotoxins do not play a major role in these reactions. Preincubation experiments suggested that there may be a population of pre-existing aggressor cells which only require linking to the targets by the mitogens for activation of their cytotoxic potential. Strong cytotoxic reactions were found with spleen cells, peripheral blood leucocytes, and bone marrow cells. Thymocytes were less active but could be stimulated for significant cytotoxicity, while bursal cells were generally unreactive. Spleen cells from agammaglobulinemic chickens totally lacking serum immunoglobulins and B cells with surface-bound immunoglobulins were as active as cells from normal chickens. The activity of spleen cells, from which phagocytic cells were removed was also unimpaired. These results indicate that the development of cytotoxic effector lymphocytes in mitogen-treated leucocyte cultures is a property of T lymphocytes. Although bone marrow cells fail to proliferate in response to these phytomitogens, they do have strong cytotoxic reactivity suggesting that different subsets of thymic-derived lymphocytes are responsible for mitogen-induced transformation and mitogen-induced cytotoxicity.

Topics: Agammaglobulinemia; Animals; Antibodies, Anti-Idiotypic; Bone Marrow; Bone Marrow Cells; Bursa of Fabricius; Cells, Cultured; Chickens; Chromium Radioisotopes; Concanavalin A; Cyclophosphamide; Cytotoxicity Tests, Immunologic; Erythrocytes; Lectins; Lymphocyte Activation; Perissodactyla; Spleen; T-Lymphocytes; Thymus Gland

Topics: Agammaglobulinemia; Cell Fractionation; Cells, Cultured; Centrifugation, Density Gradient; Concanavalin A; Humans; Lectins; Leukemia, Lymphoid; Lymphocytes; Mitogens; Mitosis; Serum Albumin, Bovine; Thymidine; Tritium

Topics: Agammaglobulinemia; Animals; B-Lymphocytes; Carbon Isotopes; Cells, Cultured; Chemotaxis; Chickens; Concanavalin A; Cyclophosphamide; Lectins; Leucine; Mitogens; Monocytes; Spleen; T-Lymphocytes