Prenatally Educated Friendly NK Cells regulate Allo-specific T cell Responses through expansion of Foxp3+CD4+Treg Cells and suppression of Type 1 and 17 CD8+T cell responses.

Abstract Prenatal alloantigen exposure during embryonic development permanently tolerizes the early gestational fetus and provides a tremendous advantage over transplantation after birth. However, influence of prenatally educated NK cells on alloantigen-specific T cell immune responses is not well elucidated. In previous experiments, we found that prenatally-educated friendly (fNK) exert suppressive effects allo-specific in vitro. We hypothesized fNK regulatory vivo. To challenge this hypothesis, examined potential through gain loss function experiments stable prenatal Balb/c --> B6.Thy1.2+ chimeras (engrafter mice). depleted both (Ly49AFG+) Thy1.2+T or alone host engrafter mice then adoptively transferred naïve responder Thy1.1+ along with donor-specific allogeneic syngeneic target into hosts. cell-replete animals exhibited higher frequency foxp3+Tregs lower allospecific T-bet+ RORγt+ CD8 compared to cell-depleted controls. Furthermore, neutralization TGF-β1 decreased cell-induced expansion Treg From these studies, conclude T-cell mediated foxp3+Treg cells. antigen experience drives emergence antigen-specific suppressors regulate responses. National Institutes Health Grant R01HL103745 Lurie Children’s Hospital Research Foundation (to A.F.S.)