Donor-derived interferon gamma separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells - PubMed (original) (raw)

. 2002 Jun 1;99(11):4207-15.

doi: 10.1182/blood.v99.11.4207.

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

Yong-Guang Yang et al. Blood. 2002.

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Abstract

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 gamma (IFN-gamma)-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-gamma. These results demonstrate that IFN-gamma 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-gamma. (Blood. 2002;99:4207-4215)

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