The effect of cyclosporine on canine lymphocyte activity

Cyclosporine is a potent new immunosuppressive agent that has an important role in organ transplantation. The exact mechanism of action of this agent is unclear. The present study was designed to demonstrate the effects of a single dose infusion of cyclosporine on canine leukocyte subsets and on the functional capabilities of T cells from these animals. The proportion of polymorphonuclear cells increased in the first 12 hr following intravenous administration of cyclosporine. There was no evidence, however, for alteration in the proportions of lymphocytes or T cells. The ability of peripheral blood mononuclear cells from a cyclosporine-treated dog to respond to T-cell mitogens varied depending on culture conditions. Washed cells cultured in pooled dog serum showed a paradoxical enhancement in responsiveness, whereas cells cultured in the presence of autologous cyclosporine-containing plasma showed significantly diminished responsiveness. Normal canine cells cultured in plasma from cyclosporine-treated dogs also showed suppressed mitogenic responses. These results indicate that cyclosporine must be present at the time of lymphocyte activation for suppression to occur. The unexpected response to T-cell mitogens by washed cells suggests that this agent affects cells, possibly at the membrane level, such that they potentially demonstrate enhanced responses to nonspecific stimuli. This latter observation may have important clinical significance for management of allograft recipients.