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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2177-2181
Involvement of Donor T-Cell Cytotoxic Effector Mechanisms in
Preventing Allogeneic Marrow Graft Rejection
Paul J. Martin,
Yoshiki Akatsuka,
Michael Hahne, and
George Sale
From the Division of Clinical Research, the Fred Hutchinson Cancer
Research Center, Seattle, WA; the Departments of Medicine and
Pathology, University of Washington, Seattle, WA; and the Institute of
Biochemistry, University of Lausanne, Epalinges, Switzerland.
Donor CD8 cells play a pivotal role in preventing allogeneic marrow
graft rejection, possibly by generating cytotoxic effectors needed to
eliminate recipient T cells remaining after the pretransplant conditioning regimen or by producing cytokines needed to support the
growth and differentiation of hematopoietic stem cells. In the present
study, we assessed the role of donor T-cell cytotoxic effector function
as a mechanism for eliminating recipient CD8 cells that cause marrow
graft rejection in mice. The ability to prevent rejection was minimally
affected by the presence of a defect in Fas ligand binding or by the
absence of granzyme B but was severely affected by the absence of
perforin. Doubly mutant perforin-deficient, Fas ligand-defective CD8
cells were completely unable to prevent rejection. Our results indicate
first that recipient CD8 effectors responsible for causing marrow graft
rejection are sensitive to cytotoxicity mediated by both perforin- and
Fas-ligand-dependent mechanisms, and second that donor T cells must
have at least one functional cytotoxic mechanism to prevent allogeneic
marrow graft rejection.
© 1998 by The American Society of Hematology.
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