Role of NKT cells in allogeneic islet graft survival

Although NKT cells expressing CD1d-reactive TCR exerted protective role in autoimmune diseases, the regulatory function of CD1d-dependent NKT cells in alloimmune responses has not been investigated thoroughly. Here, we demonstrated the regulatory effects of NKT cells using a pancreas islet transplantation model. CD40/CD154 blocking induced long-term graft survival in most B6 recipients, but B6.CD1d^-/- recipients showed co-stimulation blockade-resistant rejection. Adoptive transfer of NKT cells into B6.CD1d^-/- restored tolerizing capacity of co-stimulatory blockade. Activation of NKT cells was effective for the prolongation of graft survival and up-regulated membrane-bound TGF-β expression transiently on their cell surface. The activated CD1d-dependent NKT cells inhibited alloantigen-driven cell proliferation through cell contacts and the beneficial effect of CD154 blocking for allograft survival was related to TGF-β pathway. Thus, we can conclude that NKT cells are essential for the stable allograft survival and the regulatory function is dependent on, at least in part, TGF-β engagement.