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* Génétique, Physiopathologie et Ingériérie du Tissu Osseux, Université Nice Sophia-Antipolis, Centre National de la Recherche Scientifique, Unité de Formation et de Recherche de Médecine, Nice; and
Institut National de la Santé et de la Recherche Médicale U576, Hôpital de l’Archet, Nice, France
Natural CD25+CD4+ regulatory T cells (Treg) are essential for self-tolerance and for the control of T cell-mediated immune pathologies. However, the identification of Tregs in an ongoing immune response or in inflamed tissues remains elusive. Our experiments indicate that TIRC7, T cell immune response cDNA 7, a novel membrane molecule involved in the regulation of T lymphocyte activation, identifies two Treg subsets (CD25lowTIRC7+ and CD25highTIRC7–) that are characterized by the expression of Foxp3 and a suppressive activity in vitro and in vivo. We also showed that the CD25lowTIRC7+ subset represents IL-10-secreting Tregs in steady state, which is accumulated intratumorally in a tumor-bearing mice model. Blockade of the effect of IL-10 reversed the suppression imposed by the CD25lowTIRC7+ subset. Interestingly, these IL-10-secreting cells derived from the CD25highTIRC7– subset, both in vitro and in vivo, in response to tumoral Ags. Our present results strongly support the notion that, in the pool of natural Tregs, some cells can recognize foreign Ags and that this recognition is an essential step in their expansion and suppressive activity in vivo.
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1 This work was supported by a fellowship of the Fondation pour la Recherche Médicale (to A.W.). This work was also funded by the Centre National de la Recherche Scientifique and the Association pour la Recherche sur le Cancer.
2 Address correspondence and reprint requests to Dr. Abdelilah Wakkach, GEPITOS, Université Nice Sophia-Antipolis, Centre National de la Recherche Scientifique, Unité de Formation et de Recherche de Médecine, 28 avenue de Valombrose, 06100 Nice, France. E-mail address: wakkach{at}unice.fr
3 Abbreviations used in this paper: Treg, T regulatory cell; TIRC7, T cell immune response cDNA 7; MLN, mesenteric lymph node; DC, dendritic cell; BMDC, bone marrow-derived DC; TBM, tumor bearing mice; TFM, tumor free mice; TIL, tumor-infiltrating lymphocyte; Tr1, Treg type 1; PP, Peyer’s patches.
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