Induction of antigen-specific immune tolerance by TGF-beta-induced CD4+Foxp3+ regulatory T cells.

Like natural CD4(+)CD25(+) Treg cells, TGF-beta-induced Treg cells also prevent allograft rejection in MHC-mismatched organ transplantation models. In analyzing this effect with greater detail, we determined that injection of TGF-beta-induced, alloactivated CD4(+)CD25(+) cells induces antigen-specific immune tolerance in vivo. Increased CD4(+)CD25(+) cells in recipients contribute to this immune tolerance. In addition, adoptive transfer of TGF-beta-induced CD4(+)CD25(+) cells did not result in significant toxic and side effects in recipients. These results indicate that TGF-beta-induced, alloactivated CD4(+)CD25(+) cells may provide a safe and effective approach to protect MHC-mismatched organ grafts from rejection in a clinical setting.