Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro.

An immunosuppressive cyclic polypeptide, cyclosporin A (CyA), isolated originally from two species of fungi, prolongs organ allograft survival in several species. However, virtually nothing is known about the pharmacokinetics of this substance and its mode of action in man. We have quantified the impact of CyA on T-dependent and T-independent immunoglobulin (Ig) synthesis of human blood leukocytes in vitro, and on the proliferating capacity of the interacting lymphoid cell populations--T cells, B cells, T mu and T gamma cells. CyA inhibited all responses at approximately equal concentrations. The blast cells rather than resting lymphocytes and/or Ig-synthesizing plasma cells were incapacitated by the drug. As the phagocytosis of accessory macrophages was inhibited only at a 100--1,000-fold higher drug concentration, we conclude that CyA has a relatively specific direct effect on human T and B blast cells in vitro.