Cyclosporin A: in vivo and in vitro suppression of rat T-lymphocyte function.

Abstract

The immunosuppressive effect of cyclosporin A (CS-A) was investigated in RIC-Sprague-Dawley rats. In vivo, CS-A totally abolished the formation of antibodies to the hapten dinitrophenyl (DNP) in rats immunized with DNP-keyhole limpet haemocyanin. In vitro, the effect of CS-A was investigated in spleen cell cultures stimulated by concanavalin A, phytohaemagglutinin or lipopolysaccharide. The suppression due to CS-A was more pronounced in cultures set up with cells from rats fed the drug than in spleen cell cultures from control animals supplemented with serum containing CS-A. Purified by filtration through Degalan-rat Ig-anti IgG columns, T lymphocytes from CS-A treated rats were no longer suppressed by CS-A serum in contrast to purified T cells obtained from control rats. Thus, CS-A seems to interfere with the mitogenic triggering of a subpopulation of T lymphocytes resulting in a functional clonal deletion.