Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells.

Coupling of ovalbumin (OVA) to anti-DEC-205 monoclonal antibody (mAb) (alphaDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell-mediated hypersensitivity reactions were suppressed by the injection of alphaDEC-OVA and (2) the application of hapten-coupled alphaDEC-205 reduced CD8+ T-cell-mediated allergic reactions. Thus, targeting of antigens to immature DCs through alphaDEC antibodies led to the induction of regulatory T cells, providing the basis for novel strategies to induce regulatory T cells in vivo.