Cyclosporine inhibits soluble antigen and alloantigen presentation by human monocytes in vitro

We examined whether cyclosporine (CsA) interferes with human monocyte processing and presentation of soluble and particulate antigens. Human monocytes were pulsed in the presence of CsA with one of three antigens: tetanus toxoid (TT), diphtheria toxoid (DIP) or cytomegalovirus (CMVx). When these monocytes were co-cultured with immunocompetent T-lymphocytes they were found to be impaired in the induction of proliferative and cytotoxic T-cell responses. At CsA concentrations higher that 0.5 micrograms/ml, proliferation induced by the particulate CMVx antigen was markedly more sensitive than that induced by the soluble TT antigen. In the allogeneic mixed lymphocyte reaction (MLR), pretreatment of responder haplotype monocytes alone with CsA led to reduced reactivity as determined in both proliferative (P less than 0.01) and cell-mediated lympholysis (P less than 0.001) assays. These effects of CsA were not due to direct CsA action of residual CsA carried over with treated monocytes, and were not apparently due to inhibition of interleukin-1 (IL-1) production since exogenous IL-1 could not restore normal responses.