SUPPRESSION OF IN VITRO LYMPHOCYTE RESPONSES BY CHLOROQUINE.
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Biomedical subjects
Publications and source records attributed to K HIRSCHHORN.
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Human lymphocytes, cultured in the presence of phytohemagglutinin, undergo morphologic transformation and subsequent mitosis. Before mitosis (48 to 72 hours), a sharp increase in acid phosphatase activity occurs in cells stimulated with phytohemagglutinin. Histochemical examination of these cells demonstrates that innumerable granules containing acid phosphatase develop in the cytoplasm before mitosis. It is possible that enzymes present in granules which stain for acid phosphatase activity (lysosome-like) may play a role in phytohemagglutinin-stimulated cell division.
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Addition of phytohemagglutinin and of streptolysin S to in vitro cultures of leukocytes of normal and agammaglobulinemic subjects resulted in mitosis of lymphocytes and their differentiation to plasma cells. In contrast, specific antigens induced mitosis and differentiation of lymphocytes of normal but not of agammaglobulinemic donors. The data suggest that the absence of plasma cells in agammaglobulinemia is not in itself responsible for failure of antibody production, but is rather the morphologic concomitant of the primary defect (failure of antibody production on exposure to antigenic stimulus).
Lymphocytes from two unrelated individuals, cultured together in the same tube, undergo morphological transformation to large cells and divide. Both of these parameters may be estimated quantitatively. There is a correlation between the degree of this response and the degree of cross-reactivity of grafts from the two individuals placed on a third unrelated recipient.
Cultures of peripheral lymphocytes may be used to assay histocompatibility. The lymphocytes from potential kidney recipients are cultured with those from potential donors and the percentage of large cells and mitoses stimulated is determined. The immunologic competence of cultured lymphocytes from recipients receiving immunosuppressive therapy is evaluated by determining their responsiveness to phytohemagglutinin. Suppression of response appears to be correlated with the absence of clinical signs of graft rejection.
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Phytohemagglutinin causes cultured lymphocytes to agglutinate, divide, and produce gamma-globulin. Most cells are transformed into large lymphocytes, some resembling plasmocytes. Actinomycin D stops gamma-globulin production after 2 hours. When specific antigens are added to lymphocytes from sensitized individuals, only some cells undergo morphological transformation, produce gamma-globulin, and divide. When cells or cell extracts from an unrelated individual are added to a culture, a similar reaction occurs.
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