Inhibitory activity of cyclosporine is dependent on the activating signal(s) provided to T cells.
The effects of cyclosporine on T cell activation induced by monoclonal anti-CD3 antibodies, 12-O-tetradecanoyl phorbol-13-myristate acetate (TPA), or human recombinant interleukin 2 (IL-2) were investigated. Cyclosporine inhibited anti-CD3-mediated expression of IL-2 receptors and IL-2 factor production by peripheral blood mononuclear cells (PBM). Cyclosporine did not inhibit when TPA rather than anti-CD3 was used to activate the PBM. Effects of cyclosporine on the activation of memory T cells were also dependent on the stimulus used to activate memory T cells. Cyclosporine inhibited alloantigen associated memory T cell activation, but not when IL-2 provided the necessary triggering signal to memory T cells. IL-2-mediated memory T cell activation was inhibitable with monoclonal antibodies directed at the IL-2 receptor or at the IL-2 factor. Collectively, these findings indicate that the inhibitory activity of cyclosporine is dependent on the activating signals provided to T cells. Moreover, antibodies directed at the IL-2 system together with cyclosporine might prove to be more potent immunosuppressants than either agent alone.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D003524:Cyclosporins / Q000494:pharmacology*; D003864:Depression, Chemical; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate