EFFECT OF CYCLOSPORIN-A ON INVITRO PROLIFERATIVE ACTIVITY AND IMMUNOGLOBULIN-SYNTHESIS OF ISOLATED HUMAN LYMPHOID-CELL SUB-POPULATIONS

Abstract

Cyclosporin A [CA] inhibited at equal concentrations both pokeweed mitogen [PWM] and Staphylococcus aureus Cowan I-induced in vitro proliferative activity of blood leukocytes, intracellular Ig synthesis and of Ig release to the culture medium. When the interacting lymphoid cell subpopulations, T cells, B cells, T.gamma. and T.mu. cells were fractionated apart and separately stimulated with these mitogens, CA inhibited again at equal concentrations PWM-induced proliferation of blood T.gamma., T.mu. and B cells and Staphylococcus-induced proliferation of B cells. The 50% inhibitory concentration varied in separate experiments between 10-2-10-1 .mu.g/ml. Although CA efficiently suppressed the blastogenic response, a 100- to 1000-fold concentration of the drug was required to damage resting lymphocytes in cultures. After the blastogenic phase, PWM-stimuated blood leukocytes were again resistant to CA: intracellular Ig synthesis and Ig release to the culture medium proceeded independently of drug presence. As the phagocytic activity of mononuclear phagocytes was not affected by prior culture in CA-containing medium. Evidently in man CA suppresses both T and B lymphocyte blastogenesis, and the suppression is due to a direct effect on the blast cell rather than mediated via a 3rd-party accessory cell.