Donor-derived interferon gamma separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells.
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)
Yang
Yong-Guang
YG
Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA. yyongguang.yang@tbrc.mgh.harvard.edu
Qi
Jin
J
Wang
Min-Guang
MG
Sykes
Megan
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology
D007371:Interferon-gamma