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

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 Treg 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.