IL-10 producing T regulatory type 1 cells and oral tolerance.

Oral tolerance is mediated by multiple mechanisms such as anergy and/or active suppression of Ag-specific effector T cells by T regulatory (Tr) cells. Among the CD4+ Tr cells, T regulatory type 1 cells (Tr1) have been shown to down-modulate immune responses through production of the immunosuppressive cytokines IL-10 and TGF-?. Human Tr1 cells can be differentiated in vitro with IL-10+IFN-? or after stimulation with immature DCs or DCs rendered tolerogenic by exposure to immunomodulatory compounds. Murine Tr1 cells can be differentiated in vitro by activating naïve CD4+ T cells in the presence of high doses of IL-10. Several protocols for induction of oral tolerance, including oral administration of the antigen with IL-10, have been shown to induce Ag-specific Tr1 cells that suppress undesired immune responses toward self-Ags, allergens, and food-Ags. Overall these data demonstrate that IL-10 producing Tr1 cells play a central role in oral as well as systemic tolerance induction.