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 antigen-specific effector T cells by T regulatory (Tr) cells. Among the CD4⁺ Tr cells, T regulatory type 1 cells (Tr1) have been shown to downmodulate immune responses through production of the immunosuppressive cytokines IL-10 and TGF-β. Human Tr1 cells can be induced to differentiate in vitro by IL-10 + IFN-α or after stimulation by immature dendritic cells (DCs) or DCs rendered tolerogenic by exposure to immunomodulatory compounds. Murine Tr1 cells can be induced to differentiate in vitro by activating naive 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 antigen-specific Tr1 cells that suppress undesired immune responses toward self-antigens, allergens, and food antigens. Overall, these data demonstrate that IL-10-producing Tr1 cells play a central role in the induction of oral as well as systemic tolerance.