INHIBITION OF HUMAN MONOCYTE ANTIGEN PRESENTATION, BUT NOT HLA-DR EXPRESSION, BY CYCLOSPORINE

Abstract

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 .mu.g/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 .mu.gml. 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 antigens presentation. The mechanism of action seems to be independent of IL-1 production, PG secretion, and HLA-DR expression.