concanavalin-a and Lymphatic-Diseases

We previously showed that certain tyrphostin derivatives, known as protein tyrosine kinase inhibitors, also act as topoisomerase I-specific antagonists and inhibit Moloney murine leukemia virus replication in vitro in acutely and chronically infected cells. However, an accurate portrayal of retroviral-induced disease cannot rely exclusively on extrapolations from in vitro data. Therefore, experiments with animal models are essential for evaluating the efficacy of a specific drug in vivo. In this study, we examined the effect of tyrphostin AG-1387 on murine AIDS (MAIDS) development in C57BL/6J mice injected with the LP-BM5 virus mixture. A single dose of tyrphostin, administered together with or 24 h post virus inoculation, decreased the development of MAIDS symptoms as measured by spleen and lymph node weight, the T-cell response to concanavalin A (con A), and spleen architecture. Furthermore, weekly treatment with tyrphostins totally abolished MAIDS symptoms and prevented the viral infection of the spleen cells as measured by the absence of viral RNA and the restoration of T-cell function in these spleens. These results implicate that prolonged treatment with tyrphostins is needed for the prevention of MAIDS development in infected mice and suggest that it may be applied as a legitimate remedy for the treatment of retroviral-induced diseases.

Topics: Animals; Antiviral Agents; Blotting, Northern; Concanavalin A; Disease Models, Animal; Lymph Nodes; Lymphatic Diseases; Mice; Mice, Inbred C57BL; Moloney murine leukemia virus; Murine Acquired Immunodeficiency Syndrome; RNA, Viral; Spleen; Splenomegaly; T-Lymphocytes; Tyrphostins

It has been demonstrated that the single autosomal recessive lpr and gld genes are responsible for the accumulation of unusual T-cell subsets. Although these subsets have been assigned to the T-cell lineage, they share certain antigenic cell surface markers with mature B lymphocytes. Consequently the maturational pathway(s) of these cells has been difficult to fit in the currently accepted models of T-cell differentiation. Previous work has determined that the YE1/19.1 monoclonal antibody (mAb), developed against the EL4 tumour line, reacts with the accumulating T cells in lpr-expressing mice. In this study we report that YE1/19.1 could also be used as a marker for the accumulating T cells in gld-expressing mice and that the hyporesponsiveness seen in gld mice correlated with these accumulating cells. We then demonstrated that the YE1/19.1 antibody also reacts with a subpopulation of neonatal thymocytes as well as a mitogen non-responsive subpopulation of 'double negative' T cells from the spleens and thymuses of non-autoimmune mice. Our findings indicate that the YE1/19.1 mAb will be a useful probe for helping in the eludication of the intra-thymic maturational pathways of T lymphocytes.

Topics: Animals; Antigens, Neoplasm; Autoimmune Diseases; Cell Division; Concanavalin A; Epitopes; Immune Tolerance; Lymphatic Diseases; Lymphoma, T-Cell; Mice; Mice, Inbred C57BL; T-Lymphocyte Subsets; T-Lymphocytes

Autoimmune-prone mice homozygous for the lpr gene develop prominent lymphadenopathy composed mainly of Thy-1+ CD8- CD4- B220+ cells. Expression patterns of B220 vs CD4 on lymph node cells from lpr mice were analysed using two-colour flow microfluorometry. B220+CD4+ cells, which were hardly seen in lymph nodes of B6-+/+ mice, increased significantly in B6-lpr mice with ageing. Functional analysis of purified B220+ CD4+ cells from lpr mice revealed that these cells scarcely responded to T cell mitogens with or without rIL-2. Furthermore, B220+ CD4+ cells were defective in IL-2 production when cultured with Con A. On the other hand, B220-CD4+ cells from B6-lpr mice showed an ability to respond to T cell mitogens similar to that of B220- CD4+ cells from B6-+/+ mice. These results indicate that an unusual T cell subset expressing both B220 and CD4 in lpr mice is functionally defective, but the intrinsic ability of B220-CD4+ cells is almost intact as compared with the counterpart in normal mice.

Topics: Aging; Animals; Antigens, Differentiation, T-Lymphocyte; Concanavalin A; Interleukin-2; Leukocyte Common Antigens; Leukocyte Count; Lymphatic Diseases; Mice; Mice, Inbred C57BL; Mitosis; Phytohemagglutinins; T-Lymphocytes

The ability of cells infected with human T lymphotropic virus type III (HTLV-III) to suppress lymphocyte responses to concanavalin A (ConA) was evaluated. Thirty homosexual men, both HTLV-III seropositive and seronegative, and 11 seronegative laboratory personnel were studied. Peripheral blood lymphocytes from all groups had lower responses to ConA in the presence of HTLV-III-infected H9 cells than in the presence of uninfected H9 cells. Among HTLV-III-seropositive males, responses to ConA in the presence of infected or uninfected H9 cells correlated with the number of T4 cells present. The studies suggest that HTLV-III-infected cells can suppress normal lymphocyte responses. Possible mechanisms of this suppression are discussed.

Topics: Concanavalin A; Deltaretrovirus; Homosexuality; Humans; Immunosuppression Therapy; Lymphatic Diseases; Lymphocyte Activation; Male; Retroviridae Infections; T-Lymphocytes

Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty-seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty-two individuals had anti-LAV/HTLV-III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell-mediated immunity, inverted T-cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2- were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL-1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but may explain the uncontrolled activation of B cells.

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Bactericidal Activity; Cell Division; Concanavalin A; Dinoprostone; Female; Homosexuality; Humans; In Vitro Techniques; Interleukin-1; Lymphatic Diseases; Male; Middle Aged; Monocytes; Phagocytosis; Prostaglandins E; Substance-Related Disorders; Superoxides

Immunological and mycological investigations were carried out in 21 Swedish homosexual males. One of them had AIDS, one pre-AIDS and 19 lymphadenopathy of whom 18 fulfilled the criteria of persistent generalized lymphadenopathy (PGL) as defined by the Centers for Disease Control, Atlanta, (CDC). The patients were investigated immunologically with respect to their in vitro lymphocyte reactivity to various mitogens. The patients with AIDS and pre-AIDS belonged to the group of 8 patients with low response to mitogens. Blood helper T cell percentages and serum beta 2-microglobulin concentrations correlated with the PHA reactivity. Three patients, with the diagnoses AIDS, pre-AIDS and PGL respectively, had clinical signs of oral candidiasis with rich growth of Candida albicans in culture. These were all low responders to mitogen stimulation. Six cases of tinea pedis were diagnosed and seemed to be distributed among the patients irrespectively of the severity of their immunological disorders.

Topics: Acquired Immunodeficiency Syndrome; Adult; beta 2-Microglobulin; Candidiasis, Oral; Concanavalin A; Dermatomycoses; Homosexuality; Humans; Lymphatic Diseases; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes, Helper-Inducer; Tinea Pedis

The presence of lysozyme, alpha 1-antitrypsin (AT), alpha 1-antichymotrypsin (ACT), and cytoplasmic receptors for peanut and soy bean agglutinin and for concanavalin A (PNA, SBA, and ConA, respectively) was investigated in formalin-fixed, paraffin-embedded material from 16 cases of malignant histiocytosis. The tumors in these cases did not show phenotypic characteristics of T or B cells. Lysozyme and AT especially were found less frequently in tumor cells from malignant histiocytosis than in normal histiocytes, whereas ACT and binding sites for the lectins were maintained during malignancy. Specimens from 44 per cent of the cases were positive for lysozyme, 56 per cent for AT, 82 per cent for ACT, 88 per cent for PNA receptors, 94 per cent for SBA receptors, and 100 per cent for ConA receptors. Tumor cells from B- and T-cell lymphomas were negative for these markers. Plasma cells, granulocytes, and fibroblasts sometimes bound ConA, but not PNA or SBA. The cases of malignant histiocytosis were subdivided into three groups on the basis of grade of differentiation. The tumor cells from the cases in group 1 showed the highest degree of differentiation, those from group 2 an intermediate degree, and those from group 3 the lowest degree. Mitotic activity was present mainly in groups 1 and 2. Lysozyme was present most frequently in groups 1 and 3 and in cases with the least mitotic activity. Expression of AT was decreased in groups 2 and 3. The presence of phagocytosis, which is not obligatory for the diagnosis, was always correlated with ACT staining. The presence of binding sites for these lectins can be considered a useful marker for malignant histiocytes.

Topics: alpha 1-Antitrypsin; Chymotrypsin; Concanavalin A; Histiocytes; Histocytochemistry; Humans; Immunoenzyme Techniques; Lectins; Lymphatic Diseases; Mitosis; Muramidase; Peanut Agglutinin; Phagocytosis; Plant Lectins; Receptors, Mitogen; Soybean Proteins

Topics: Acquired Immunodeficiency Syndrome; Concanavalin A; Diarrhea; Humans; Inosine; Inosine Pranobex; Lymphatic Diseases; Lymphocyte Activation; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes

A patient with Sézary syndrome developed a diffuse undifferentiated lymphoma of T-cell origin. After becoming resistant to multiple chemotherapeutic agents, the patient was treated with antithymocyte globulin. A 75% reduction in adenopathy and complete resolution of skin erythema was observed during an 8-day period. In addition the percent of circulating T cells and the ability of those cells to respond to phytohemagglutinin and concanavalin A were reduced after antithymocyte globulin therapy. The patient died of an intracerebral hemorrhage secondary to profound thrombocytopenia. The study suggests that tumor lysis may be achieved by passive antibody therapy in certain advanced lymphomas.

Topics: Antilymphocyte Serum; Concanavalin A; Dermatitis, Exfoliative; Humans; Immunotherapy; Keratoderma, Palmoplantar; Lectins; Lymphatic Diseases; Lymphocyte Activation; Lymphoma; Male; Middle Aged; Syndrome; T-Lymphocytes

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