Therapeutic potential of self‐antigen‐specific CD4+CD25+ regulatory T cells selected in vitro from a polyclonal repertoire

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