Allo-specific NK cells differentially regulate T cell allo-immunity depending on prenatal education

Abstract

Allospecific NK cell hyporesponsiveness develops after in utero hematopoietic cellular transplantation (IUHCT) in mice who exhibit stable long-term engraftment. Conversely, allospecific NK cell responses are normal in mice that reject their graft. We hypothesized that these alternate NK cell responses also differentially influence T cell responses after IUHCT. To challenge this hypothesis, we compared the helper or suppression potential of prenatally educated NK cells between prenatal recipients with stable engraftment (engrafter mice) and littermates that rejected their graft (rejecter mice) in a Balb/c --- > a B6 model of IUHCT. Allospecific NK cells from engrafter, rejecter, or naïve mice were co-cultured with naïve responder T cells (B6) and irradiated allogeneic target cells (Balb/c) in an in vitro IFN-g assay. Intracellular production of IFN-g was measured by flow cytometry of the naïve responder T cells after 66 hrs of co-culture. We found that responder T cells displayed increased IFN-gamma production when co-cultured with allospecific NK cells from rejecter mice compared to co-culture with allospecific NK cells from naive control mice. Conversely responder T cells displayed decreased IFN-g production when co-cultured with allospecific NK cells from engrafter mice compared to co-culture with NK cells from naïve control mice. From these results, we conclude that allospecific NK cells can influence the allospecific response of T cells in vitro depending on the context of their prenatal education. Further studies are needed to determine if similar mechanisms support engraftment or rejection in vivo.