The effects of Immunosuppressive agents on NK cell function (102.18)

Abstract

Abstract Natural killer (NK) cells are potent effector cells in allogeneic bone marrow and xeno transplantation. NK cells infiltrate solid organ allografts and a role for NK cells in acute and chronic rejection has been suggested. Little is known about the effects of immunosuppressive agents on NK cells Primary NK cell lines were analyzed for proliferation in the absence or presence of increasing doses (0–100 ng/ml) of cyclosporine (CSA), FK506 (FK) or Rapamycin, (RAPA). NK cells demonstrated robust proliferation both in the absence and presence of CSA and FK. In contrast, RAPA significantly (p< 0.05) inhibited the proliferation of NK cells in a dose-dependent manner. The effects of immunosuppressive agents on NK cells were determined in a rat liver transplant model. Peripheral NK cell levels in graft recipients treated with CSA and FK remained stable whereas there was a marked decrease in the levels of NK cells in recipients treated with RAPA. The immunosuppressive agents did not alter IFNγ production by NK cells however NK cell–mediated cytotoxicity was significantly (p< 0.05) inhibited in the presence of RAPA (but not CSA or FK). These data indicate that CSA and FK have little effect on NK cell function. In contrast, NK cell proliferation and function are significantly decreased in the presence of RAPA. Understanding the differential effects of immunosuppressive drugs on NK cell function is important in clinical transplantation.