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


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 NK cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor T cells or host DCs by the IL-12/15/18-preactivated NK cells, proliferation of donor T cells was inhibited. Strikingly, the graft versus leukemia effect mediated by donor T cells was retained, resulting in improved overall survival of mice that received lymphoma cells, donor allogeneic T cells, and IL-12/15/18-preactivated NK cells. These results suggest that IL-12/15/18-preactivated NK cells 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.

SUBMITTER: Huber CM 

PROVIDER: S-EPMC4687420 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Hüber Christian M CM   Doisne Jean-Marc JM   Colucci Francesco F  

European journal of immunology 20150417 6


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 NK cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor T cells or host DCs by the IL-12/15/18-preactivated N  ...[more]

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