CD4⁺CD25⁺ regulatory T cells (T_reg) play a major role in the prevention of autoimmune diseases. Converging evidence indicates that T_reg specific for self‐antigens expressed by target tissues have a greater therapeutic potential than polyclonal T_reg. Therefore, the selective expansion of rare self‐antigen‐specific T_reg naturally present in a polyclonal repertoire of T_reg is of major importance. In this work, we investigated the potential of different dendritic cell (DC) subsets to expand antigen‐specific T_reg in mice. The in vitro selective expansion of rare islet‐specific T_reg from polyclonal T_reg could only be achieved efficiently by stimulation with CD8⁺ splenic DC presenting islet antigens. These islet‐specific T_reg exerted potent bystander suppression on diabetogenic T cells and prevented type 1 diabetes. This approach opens new perspectives for cell therapy of autoimmune diseases.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200635967