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European journal of immunology

IL-12/15/18-preactivated NKxa0cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation.


PMID 25778912

Abstract

Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus host disease (GvHD). Here, we show that adoptively transferred IL-12/15/18-preactivated NKxa0cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NKxa0cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor Txa0cells or host DCs by the IL-12/15/18-preactivated NKxa0cells, proliferation of donor Txa0cells was inhibited. Strikingly, the graft versus leukemia effect mediated by donor Txa0cells was retained, resulting in improved overall survival of mice that received lymphoma cells, donor allogeneic Txa0cells, and IL-12/15/18-preactivated NKxa0cells. These results suggest that IL-12/15/18-preactivated NKxa0cells may be useful in improving immunotherapy of mismatched hematopoietic cell transplantation. Compared with previously proposed protocols, our findings suggest that in vitro NK-cell preactivation with this cytokine cocktail offers the significant advantage that cytokines do not need to be administered systemically to sustain NK-cell activity, thus avoiding toxicity.