Antigen-specific induction of regulatory T cells in vivo and in vitro.

The peripheral induction of Foxp3-expressing regulatory T cells outside the thymus is required in order to maintain local homeostasis in distinct microenvironments such as the gut. Extrathymic induction of Treg may also be exploited to prevent unwanted immune responses. Here, we discuss the methodology allowing for the stable de novo generation of Tregs specific for foreign antigens in peripheral lymphoid tissue via subimmunogenic peptide delivery using either peptide contained in fusion antibodies directed against the DEC205 endocytotic receptor on steady-state dendritic cells or the implantation of peptide-delivering osmotic mini-pumps. Furthermore, we also address methods in order to achieve TGFβ-dependent Treg conversion in vitro, thereby mainly focusing on the role of retinoic acid (RA) to enhance TGFβ-dependent conversion into Tregs.