Studies on the mechanism of action of cyclosporin A.

The mechanism of cyclosporin A (CS-A), a compound known to act selectively on the immunocompetent lymphocyte, was investigated in a series of in vitro studies. CS-A, provided it was added simultaneously with mitogen, inhibited the incorporation of tritiated uridine and thymidine into mouse spleen cells and human peripheral blood lymphocytes. Addition of CS-A 48 h after onset of culture did not affect cell division, indicating that it acted at an early stage of lymphocyte stimulation, exerted no inhibitory effect on lymphoblasts and did not possess anti-mitotic activity. It was further shown that CS-A was not lymphotoxic and that its effect was reversible, because suppressed spleen cells recovered their proliferative capacity after a 24 h elution period. Inhibition of PFC in the Mishell-Dutton assay provides evidence of an anti-T helper cell action of CS-A.