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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4207-4215
TRANSPLANTATION
Donor-derived interferon  separates graft-versus-leukemia
effects and graft-versus-host disease induced by donor CD8 T
cells
Yong-Guang Yang,
Jin Qi,
Min-Guang Wang, and
Megan Sykes
From the Bone Marrow Transplantation Section,
Transplantation Biology Research Center, Surgical Service,
Massachusetts General Hospital/Harvard Medical School, Boston, MA.
The graft-versus-leukemia (GVL) effects and graft-versus-host
disease (GVHD)-inducing activity of CD8 T cells was compared in murine
recipients of wild-type (WT) or interferon  (IFN-)-deficient (GKO) allogeneic donor cells. CD8 T cells (or CD4-depleted splenocytes) from GKO donor mice induced more severe GVHD in lethally irradiated allogeneic recipients compared to the same cell populations from WT
donors. Consistent with GVHD severity, donor CD8 T-cell expansion in
allogeneic recipients was augmented in the absence of IFN-. These
results demonstrate that IFN- does not stimulate but instead down-modulates GVHD induced by donor CD8 T cells. Remarkably, antihost
lymphohematopoietic reactions, including GVL effects against host
leukemia/lymphoma cells, of CD8 T cells correlated inversely with their
GVHD-inducing activity, and those of GKO donors were markedly weaker
than those mediated by WT donor CD8 T cells. These data show for the
first time that GVHD-inducing activity and GVL effects of allogeneic
CD8 T cells can be separated by a single cytokine, IFN-.
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