Cyclosporine inhibits protein kinase C-dependent signals in human peripheral blood lymphocytes

T helper lymphocyte activation is thought to occur when the T₃T₁ receptor is activated by antigen, and a calcium signal and stimulus to protein kinase C appear to be essential for interleukin-2 production and lymphocyte proliferation. Previous work from our lab has demonstrated that the calcium signal is unaffected by cyclosporine. In this report, a macrophage and T suppressor/cytotoxic-depleted population of human peripheral blood mononuclear cells is stimulated with Sepharose beads bound to OKT3 monoclonal antibody and Sepharose-OKT3 plus a phorbol ester (a stimulus to protein kinase C). Cyclosporine inhibits both the Sepharose/OKT3-mediated and Sepharose/OKT3/phorbol myristic acetate-mediated mitogenesis. Cyclosporine inhibits either protein kinase C or protein kinase C-dependent intracellular signals necessary for T helper activation and proliferation.