Prevention of marrow graft rejection without induction of graft-versus-host disease by a cytotoxic T-cell clone that recognizes recipient alloantigens.
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 H2(d) alloantigens. Three of the clones caused no overt toxicity when as many as 20 x 10(6) cells were infused intravenously into irradiated H2(d)-positive recipients, and one clone caused acute lethal toxicity within 1 to 3 days after transferring 10 x 10(6) cells into H2(d)-positive recipients. One clone that did not cause toxicity was able to prevent rejection of (C57BL/6J x C3H/HeJ)F1 marrow in 800 cGy-irradiated (BALB/cJ x 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.
Kusunoki
Y
Y
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Chen
W
W
Martin
P J
PJ
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016207:Cytokines; D006183:H-2 Antigens; D007519:Isoantigens