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.
McMillen
M A
MA
Department of Surgery, Yale University, New Haven, Connecticut 06520.
Schaefer
H A
HA
MacArthur
J D
JD
Adrian
T A
TA
Modlin
I M
IM
D000911:Antibodies, Monoclonal / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012685:Sepharose; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D012685:Sepharose; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate