Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2821-2826 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 104 |
Issue number | 8 |
DOIs | |
State | Published - Feb 20 2007 |
Keywords
- Antigen-presenting cells
- Autoimmunity
- Nonobese diabetic (NOD) mice
- Type 1 diabetes
ASJC Scopus subject areas
- General