Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells

YG Yang, J Qi, MG Wang… - Blood, The Journal of the …, 2002 - ashpublications.org
YG Yang, J Qi, MG Wang, M Sykes
Blood, The Journal of the American Society of Hematology, 2002ashpublications.org
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 γ
(IFN-γ)–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 …
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 γ (IFN-γ)–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-γ. These results demonstrate that IFN-γ 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-γ.
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