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Prevention of allogeneic marrow graft rejection by donor T cells that do
not recognize recipient alloantigens: potential role of a veto mechanism
PJ Martin
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104, USA.
Clinical trials and experimental studies have demonstrated that donor T
cells can play a critical role in preventing allogeneic marrow graft
rejection. Results of a previous study showed that donor T cells were most
effective for preventing rejection when they recognize an alloantigen
expressed by recipient T cells and can cause graft-versus- host disease
(GVHD). The present study examined models where marrow graft rejection can
be prevented by donor T cells that do not recognize host alloantigens and
cannot cause GVHD. Donor T cells prevented rejection of major
histocompatibility complex (MHC) class I and II- disparate F1 marrow in
parental recipients prepared with > or = 800 cGy total body irradiation
(TBI) but not in those prepared with < or = 750 cGy TBI. In recipients
prepared with high TBI exposures, rejection was mediated entirely by host
CD8 cells. With lower TBI exposures, rejection was mediated by host CD4
cells and CD8 cells. These observations suggested the hypothesis that donor
T cells prevent rejection mediated by host effectors that recognize donor
MHC class I alloantigens but do not prevent rejection mediated by host
effectors that recognize donor class II alloantigens. Consistent with this
hypothesis, further experiments showed that F1 donor T cells can prevent
rejection of MHC class I-disparate marrow in irradiated parental recipients
but have no detectable effect on rejection of MHC class II-disparate
marrow. We propose that the expression of MHC class I molecules on donor T
cells makes it possible for these cells to inactivate the host response
against donor class I alloantigens through a veto mechanism, whereas the
absence of MHC class II molecules on murine T cells explains why these
cells cannot inactivate the host response against donor class II
alloantigens. Finally, donor CD4 cells and CD8 cells were equivalently
effective for preventing rejection of F1 marrow in parental recipients,
suggesting that veto activity is not restricted solely to the CD8 subset of
murine T cells. A veto mechanism could enable donor T cells to prevent
allogeneic marrow graft rejection without causing GVHD.
Volume 88,
Issue 3,
pp. 962-969,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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