TGF-β1 can convert hostile NK cells to friendly NK cells via downregulation of an activating receptor and upregulation of inhibitory receptors 2260153

Introduction In prenatal allotransplantation (Balb/c to C57BL/6), NK cells play a critical role in engraftment or rejection of graft in recipients. Adoptively transferred naïve hostile (Ly49D-AFG+) NK cells were converted into friendly phenotype (Ly49D+AFG+) in tolerant engrafter chimera mice. Therefore, we hypothesized that hostile NK cells can be converted into tolerant NK cells in tolerogenic (abundant TGF-b1) environment. Methods To test this hypothesis, isolated naïve hostile NK cells were cultured with allogeneic target cells in the presence e of high dose (1ng/ml) TGF-b1 or anti-CD48 antibody that stimulate NK cells to produce TGF-b. A week later, we analyzed the frequencies of activating NK cell receptor (Ly49D) and inhibiting receptor (Ly49A, F, and G) in hostile NK cell population. Results We found that hostile NK cells cultured with anti-CD48 and allogeneic target cells, expressed inhibitory receptor (Ly49AFG+) but decreased the frequency of activating receptor, Ly49D in hNK cell population. High dose TGF-b1 can convert hostile NK cells to friendly NK cells no matter with or without allo stimulation. Conclusion These results prove that NK cell tolerance can arise from down-regulation of activating receptor and/or expressing inhibitory receptors upon stimulation with allogeneic target cells in tolerogenic environment (presence of TGF-b1). It provides a possible tolerance therapy to protect graft in rejecting recipient following prenatal allo transplantaion. Funding Source Ann & Lurie Children’s Hospital research fund Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)