IMMUNOLOGICAL STUDIES ON RENAL TRANSPLANTATION

III. Experimental Studies on the Immunosuppressive Action of Cyclosporin A

Abstract

Effect of Cyclosporin A on human lymphocyte responses and antibody production in rats were studied. MLC was performed by responder cells cocultured with mitomycin treated stimulator cells for five days. Twenty hours before harvesting, ³H-TdR was added. Mitogenic stimulation of lymphocytes was performed in the same procedure. CML was assayed by incubating cells from macro-MLC for four hours with PHA stimulated cells labeled with ⁵¹Cr (E/T=50/1).
Cyclosporin A showed dose-dependent inhibition of lymphocyte blastogenesis in primary and secondary MLC and mitogenic stimulation. CML assay showed that cyclosporin A inhibited the generation of cytotoxic lymphocytes. Lymphocytes harvested from MLC with cyclosporin A showed suppressive effect of CML when these lymphocytes were added to the effector phase. It may indicate the presence of suppressor cells.
Cyclosporin A inhibited antibody production in rats. Though cyclosporin A was administered only for the first seven days, after reimmunization at three weeks, antibody production was inhibited to the same degree. It is considered that cyclosporin A is important at the early stage of antigenic stimulation or some immunological tolerance may be induced.
It is accepted that allogenic MLC or Con A stimulation of lymphocytes induce suppressor T cells. Con A induced suppressor T cells have an ability to form rosette with autologous erythrocytes. In the allogenic MLC with or without cyclosporin A, the number of autorosetting cells increased, which had a suppressive effect on MLC. Cyclosporin A is considered to have no inhibitory effect on the generation of suppressor T cells.
In allogenic MLC with cyclosporin A, macrophage-like adherent cells, which suppressed MLC, increased in number. Generation of macrophage-like cells may be one of the immunosuppressive mechanisms of cyclosporin A.