Immunosuppressive activity of 4-O-methylascochlorin.

A major strategy for suppressing immune responses is the elimination of antigen-reactive lymphocytes through apoptosis. 4-O-Methylascochlorin (MAC) is a methylated derivative of a prenyl-phenol antibiotic, ascochlorin. MAC induces apoptosis in various lymphocyte cell lines. We found that MAC strongly suppressed killer T-cell activity induced by allogenic skin grafts. MAC did not suppress the killer T-cell activity induced by intraperitoneal injection of live allogenic tumor cells bearing both class I and II MHC. MAC suppressed IL-2 production of splenocytes from allogenic skin-implanted mice when induced by specific spleen adherent cells, but not by antibodies for T-cell receptor epsilon. These results suggest that MAC suppresses the antigen presentation process of alloantigen that is mediated by professional antigen presenting cells. MAC significantly increased the survival time of allogenic skin implanted on the flank mice. These results suggest that MAC may be clinically useful as an immunosuppressant that targets the antigen presentation process.