TGF-β regulatesin vivoexpansion of Foxp3-expressing CD4+CD25+regulatory T cells responsible for protection against diabetes
- 18 March 2004
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (13), 4572-4577
- https://doi.org/10.1073/pnas.0400810101
Abstract
CD4+CD25+ regulatory T cells are essential in the protection from organ-specific autoimmune diseases. In the pancreas, they inhibit actions of autoreactive T cells and thereby prevent diabetes progression. The signals that control the generation, the maintenance, or the expansion of regulatory T cell pool in vivo remain poorly understood. Here we show that a transient pulse of transforming growth factor β (TGF-β) in the islets during the priming phase of diabetes is sufficient to inhibit disease onset by promoting the expansion of intraislet CD4+CD25+ T cell pool. Approximately 40–50% of intraislet CD4+ T cells expressed the CD25 marker and exhibited characteristics of regulatory T cells including small size, high level of intracellular CTLA-4, expression of Foxp3, and transfer of protection against diabetes. Results from in vivo incorporation of BrdUrd revealed that the generation of a high frequency of regulatory T cells in the islets is due to in situ expansion upon TGF-β expression. Thus, these findings demonstrate a previously uncharacterized mechanism by which TGF-β inhibits autoimmune diseases via regulation of the size of the CD4+CD25+ regulatory T cell pool in vivo.Keywords
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