Prevention of Marrow Graft Rejection Without Induction of
Graft-Versus-Host Disease by a Cytotoxic T-Cell Clone That Recognizes
Recipient Alloantigens
Yoichiro Kusunoki,
Wei Chen, and
Paul J. Martin
From the Division of Clinical Research, the Fred Hutchinson Cancer
Research Center; and the Department of Medicine, University of
Washington, Seattle, WA.
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 × 106
cells 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.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4038-4044
© 1998 by The American Society of Hematology.
