Inhibition of human monocyte antigen presentation, but not HLA-DR expression, by cyclosporine.
The effects of cyclosporine (CsA) on antigen-dependent human T cell proliferation have been studied using tetanus toxoid as the antigen. CsA significantly inhibited antigen-dependent T cell proliferation at concentrations as low as 0.1 microgram/ml. In dissecting this system we found that preexposure of separated monocytes to CsA during the period of antigen processing led to a marked inhibition of proliferation of T cells added subsequently to the monocytes. We investigated whether this suppressive effect on monocyte antigen presentation was related to monocyte HLA-DR expression, interleukin 1 (IL-1) production, or prostaglandin (PG) secretion. None of these functions seemed to be affected by CsA. In particular, human monocyte HLA-DR expression was not inhibited by CsA, even at concentration of 10 micrograms/ml. The addition of exogenous IL-1 or indomethacin did not reverse the inhibitory effects of CsA. These experiments demonstrate that CsA inhibits antigen-dependent human T cell proliferation, at least in part by acting directly on human monocytes to inhibit antigen presentation. The mechanism of action seems to be independent of IL-1 production, PG secretion, and HLA-DR expression.
D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011453:Prostaglandins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D003524:Cyclosporins; D006684:HLA-DR Antigens; D007375:Interleukin-1; D011453:Prostaglandins; D007371:Interferon-gamma; D007213:Indomethacin