Prevention of Marrow Graft Rejection Without Induction of Graft-Versus-Host Disease by a Cytotoxic T-Cell Clone That Recognizes Recipient Alloantigens

Abstract

Abstract In allogeneic marrow transplantation, donor T cells that recognize recipient alloantigens prevent rejection but also cause graft-versus-host disease (GVHD). To evaluate whether the ability to prevent marrow graft rejection could be dissociated from the ability to cause GVHD, we generated a panel of four different CD8 cytotoxic T-lymphocyte clones specific for H2d alloantigens. Three of the clones caused no overt toxicity when as many as 20 × 106 cells were infused intravenously into irradiated H2d-positive recipients, and one clone caused acute lethal toxicity within 1 to 3 days after transferring 10 × 106cells into H2d-positive recipients. One clone that did not cause toxicity was able to prevent rejection of (C57BL/6J × C3H/HeJ)F1 marrow in 800 cGy-irradiated (BALB/cJ × C57BL/6J)F1 recipients without causing GVHD. Large numbers of cells and exogenously administered interleukin-2 were required to prevent rejection. These results with different CD8 clones suggest that GVHD and prevention of rejection could be separable effects mediated by distinct populations of donor T cells that recognize recipient alloantigens.