Effect of cyclosporin A on in vitro proliferative activity and immunoglobulin synthesis of isolated human lymphoid cell subpopulations.

Cyclosporin A inhibited at equal concentration both pokeweed mitogen and Staphylococcus aureus Cowan I-induced in vitro proliferative activity of blood leucocytes, intracellular immunoglobulin synthesis and release of immunoglobulin to the culture medium. When the interacting lymphoid cell subpopulations, T cells, B cells, T gamma and T micro cells were fractionated apart and separately stimulated with these mitogens, cyclosporin A inhibited again at equal concentrations pokeweed mitogen-induced proliferation of blood T gamma, T micro and B cells and Staphylococcus-induced proliferation of B cells. The 50% inhibitory concentration varied in separate experiments between 10(-2)-10(-1) microgram/ml. Although cyclosporin A efficiently suppressed the blastogenic response, a 100- to 1,000-fold concentration of the drug was required to damage resting lymphocytes in culture. After the blastogenic phase, pokeweed mitogen-stimulated blood leucocytes were again resistant to cyclosporin A: intracellular Ig synthesis and release of Ig to the culture medium proceeded independently of the presence of the drug. As the phagocytic activity of mononuclear phagocytes was not affected by prior culture in cyclosporin A-containing medium, we conclude that in man cyclosporin A suppression both T and B lymphocyte blastogenesis, and that the suppression is due to a direct effect on the blast cell rather than mediated via a third-party accessory cell.