Abstract

© 2015 by The American Society of Hematology.In allogeneic hematopoietic stem cell transplantation, controlling graft-versus-host disease while maintaining graft-versus-tumor responses is of critical importance. Using a mouse model of allogeneic HSCT, we hereby demonstrate that NKG2D expression by CD8 + T cells plays a major role in mediating GVHD and GVT effects by promoting the survival and cytotoxic function of CD8 + T cells. The expression of NKG2D ligands was not induced persistently on normal tissues of allogeneic HSCT-recipient mice treated with anti-NKG2D antibody, suggesting that transient NKG2D blockade might be sufficient to attenuate GVHD and allow CD8 + T cells to regain their GVT function. Indeed, short-term treatment with anti-NKG2D antibody restored GVT effects while maintaining an attenuated GVHD state. NKG2D expression was also detected on CD8 + T cells from allogeneic HSCT patients and trended to be higher in those with active GVHD. Together, these data support a novel role for NKG2D expression by CD8 + T cells during allogeneic HSCT, which could be potentially therapeutically exploited to separate GVHD from GVT effects.