The cellular target of cyclosporin A action in humans

The balance of immunoregulatory T-helper (TH) and T-suppressor (Ts) lymphocytes was assessed in recipients of living donor and cadaveric grafts treated with azathioprine (Az) or cyclosporin A (CyA). Enumeration of each subpopulation was performed with monoclonal OKT antibodies. While Az-treated patients had a normal ratio of circulating peripheral blood helper-inducer (OKT4+) to suppressor-cytotoxic (OKT8+) cells, recipients treated with CyA showed a reduced ratio resulting from a decreased number of TH cells with normal numbers of Ts cells. The functional activity of Ts cells was evaluated by their capacity to suppress the primary mixed lymphocyte culture response of a normal, unrelated individual. Az-treated recipients showed greater suppression than the CyA-treated group, hemodialysis patients, or normal individuals. The function of TH cells was evaluated by the capacity of isolated patient peripheral blood T cells to promote pokeweed mitogen--driven immunoglobulin release by normal B cells, which then produced hemolytic plaques.l TH function was depressed in CyA-treated but not Az-treated recipients as compared with normal individuals. These results demonstrate distinctive profiles of immunoregulatory cells in patients immunosuppressed with Az or CyA. On the one hand, successfully engrafted Az-treated patients showed enhanced suppressor-cell activity with normal helper activity. On the other hand, CyA-treated patients had reduced helper-cell function with activity. On the other hand, CyA-treated patients had reduced helper-cell function with modestly increased suppressor-cell activity. These findings may provide guidelines for the selection of and parameters for monitoring the therapeutic efficacy of immunosuppressive agents in allograft recipients.