Immune tolerance induced by intravenous transfer of immature dendritic cells via up-regulating numbers of suppressive IL-10+ IFN-γ+-producing CD4+ T cells

摘要

Dendritic cells (DCs) regulate immunity and immune tolerance in vivo. However, the mechanisms of DC-mediated tolerance have not been fully elucidated. Here, we demonstrate that intravenous (i.v.) transfer of bone marrow-derived DCs pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide blocks the development of experimental autoimmune encephalomyelitis in C57BL/6J mice. i.v. transfer of MOG-pulsed DCs leads to the down-regulation of the production of IL-17A and IFN-γ and up-regulation of IL-10 secretion. The development of regulatory T cells (Tregs) is facilitated via up-regulation of FoxP3 expression and production of IL-10. The number of suppressive CD4+IL-10 +IFN-γ+ T cells is also improved. The expression of OX40, CD154, and CD28 is down-regulated, but the expression of CD152, CD80, PD-1, ICOS, and BTLA is up-regulated on CD4+ T cells after i.v. transfer of immature DCs. The expression of CCR4, CCR5, and CCR7 on CD4 + T cells is also improved. Our results suggest that immature DCs may induce tolerance via facilitating the development of CD4+FoxP3 + Tregs and suppressive CD4+IL-10+IFN- γ+ T cells in vivo.