Abstract

CD4+CD25+Foxp3+ regulatory T cells (Treg) mediate immunologic self-tolerance and suppress immune responses. In the gut, a subset of dendritic cells is specialized to induce Treg in a transforming growth factor-ß (TGF-ß)- and retinoic acid (RA)-dependent manner. The aim of this study was to establish if RA synergizing with TGF-ß induced antigen specific CD4+ CD25high Foxp3+ Treg portraying gut homing receptors. Splenic CD4+CD25- Foxp3- naïve T cells from DO11.10 mice were cocultured with splenic CD11c+ dendritic cells from Balb/c mice in the presence of TGF-ß, RA, and low levels of an antigenic peptide. After 5 days of culture, cells were analyzed for the expression of Foxp3 and the gut homing receptors CCR9 and a4ß7. The number of Foxp3+ T cells generated with TGF-ß and RA was at least 3 times higher than in the cultures with TGF-ß alone and 15 times higher than in controls without exogenous cytokines. Also, supplementation of the cultures with RA induced the expression of the intestinal homing receptors CCR9 and a4ß7. Our results showed that coculture of naïve T cells with antigen-presenting cells in the presence of TGF-ß and RA represents a powerful approach to generate Treg with specific homing receptors. © 2009 Elsevier Inc. All rights reserved.