SUPPRESSOR CELLS IN RHESUS MONKEYS TREATED WITH ANTITHYMOCYTE GLOBULIN

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Abstract
Treatment of rhesus monkey skin allograft recipients with a brief course of rabbit antithymocyte globulin (ATG) produces an enduring immunosuppressive effect on the cellular immune system. Despite early recovery of circulating T cells, in vitro mitogen-induced lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) remain abnormally depressed for months. Depressed mitogen-induced lymphoproliferative responses in these animals are attributable to regulatory effects of adherent PBMC. Removal of the adherent fraction of PBMC on Sephadex G-10 produced a significant restoration of the mitogen-induced lymphoproliferative responses in ATG-treated monkeys. Addition of the prostaglandin synthetase inhibitor indomethacin to cultures of unfractionated PBMC from these animals also caused a significant recovery of the lymphoproliferative response. Indomethacin did not enhance the response of control animals or the response of the nonadherent PBMC fraction of ATG-treated animals. A prostaglandin-dependent mechanism may be involved in the suppressive action of the adherent cells. PBMC from ATG-treated monkeys cocultured with normal cryopreserved autologouos cells induced a dose-dependent suppression in the response to both concanavalin A and phytohemagglutinin. The suppressive activity depended upon the adherent cell fraction and was resistant to low-dose .gamma. irradiation. Administration of rabbit ATG induces nonspecific suppressor cells in the rhesus monkey. Preliminary characterization studies suggest the involvement of suppressor monocytes. The possible role of this suppressor cell system in the immunosuppressive action of rabbit ATG is discussed.