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Inhibition of T and B lymphocyte proliferation by rapamycin.


Anti-Bacterial Agents, pharmacology, B-Lymphocytes, immunology, Cell Division, drug effects, Cells, Cultured, Cyclosporins, Drug Interactions, Immunosuppressive Agents, Lymphocyte Activation, Tacrolimus, Male, Mice, Mice, Inbred CBA, Mitogens, Polyenes, Sirolimus, Swine, T-Lymphocytes, Animals

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      The immunosuppressive macrolide rapamycin shows marked structural similarity to FK-506, and like FK-506 inhibits the activation of cultured T and B lymphocytes at concentrations as low as 10(-10) M. However, rapamycin blocks T-lymphocyte proliferation at a much later stage than FK-506. It also inhibits human, porcine and murine T- and B-lymphocyte activation by all pathways tested, including pathways which are insensitive to FK-506, such as interleukin-2 (IL-2)-mediated proliferation of IL-2-dependent T-cell lines, activation of human peripheral blood T lymphocytes by phorbol ester and anti-CD28 and activation of murine B lymphocytes by bacterial lipopolysaccharide. Thus these two macrolides that bind competitively to the same major intracellular receptor protein inhibit T- and B-lymphocyte activation by quite distinct mechanisms.

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