NON-HOST-REACTIVE DONOR CD8(-CELLS OF TC2 PHENOTYPE POTENTLY INHIBIT MARROW GRAFT-REJECTION() T)

Donor CD8(+) T cells capable of host reactivity inhibit marrow graft r ejection, but also generate graft-versus-host disease (GVHD). To evalu ate whether the Tc1- and Tc2-type subsets of CD8 cells might inhibit r ejection without host reactivity, we established an F1 into-parent mur ine bone marrow transplant model. Donor Tc1 and Tc2 cells were generat ed that preferentially secreted type I or type II cytokines; both subs ets possessed potent cytolytic function, and clonally deleted host-typ e allospecific precursor CTL in vitro, B6 hosts receiving 950 cGy irra diation did not reject the donor marrow (F1 chimerism of 78.6%; n = 10 ), whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chi merism; n = 8). At 650 cGy irradiation, the addition of Tc2 cells to t he F1 marrow resulted in extensive F1 chimerism (70.8%) in 8 of 8 reci pients; in contrast, alloengraftment was not consistently observed in mice receiving Tc1 cells or unmanipulated CD8 cells. Furthermore, when the preparative regimen was further reduced to 600 cGy, only hosts re ceiving the Tc2-type cells did not reject the F1 marrow. We conclude t hat Tc2 cells potently inhibit marrow graft rejection without inducing an alloaggressive response and that non-host-reactive Tc2 cells there fore facilitate engraftment across genetic barriers with reduced GVHD. (C) 1998 by The American Society of Hematology.