antigen presenting cell, autoimmunity, diabetes mellitus, dendritic cell, pancreas islet, spleen
CD4+CD25+Foxp3+ regulatory T cells (T regs) are important for preventing autoimmune diabetes and are either thymic-derived (natural) or differentiated in the periphery outside the thymus (induced). Here we show that β-cell peptide-pulsed dendritic cells (DCs) from nonobese diabetic (NOD) mice can effectively induce CD4 +CD25+Foxp3+ T cells from naïve islet-specific CD4+CD25- T cells in the presence of TGF-β1. These induced, antigen-specific T regs maintain high levels of clonotype-specific T cell receptor expression and exert islet-specific suppression in vitro. When cotransferred with diabetogenic cells into NOD scid recipients, T regs induced with DCs and TGF-β1 prevent the development of diabetes. Furthermore, in overtly NOD mice, these cells are able to significantly protect syngeneic islet grafts from established destructive autoimmunity. These results indicate a role for DCs in the induction of antigen-specific CD4+CD25+Foxp3+ T cells that can inhibit fully developed autoimmunity in a nonlymphopoenic host, providing an important potential strategy for immunotherapy in patients with autoimmune diabetes.
Luo, X., K. V. Tarbell, H. Yang, K. Pothoven, S. L. Bailey, R. Ding, R. M. Steinman, and M. Suthanthiran. 2007. "Dendritic Cells with TGF-β1 Differentiate Naïve CD4 +CD25- T Cells into Islet-Protective Foxp3+ Regulatory T Cells." Proceedings of the National Academy of Sciences of the United States of America 104 (8): 2821-2826