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.