Characterization of IL-10-secreting T cells derived from regulatory CD4+CD25+ cells by the TIRC7 surface marker.
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 (CD25(low)TIRC7(+) and CD25(high)TIRC7(-)) that are characterized by the expression of Foxp3 and a suppressive activity in vitro and in vivo. We also showed that the CD25(low)TIRC7(+) 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 CD25(low)TIRC7(+) subset. Interestingly, these IL-10-secreting cells derived from the CD25(high)TIRC7(-) 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.
Wakkach
Abdelilah
A
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, 28 avenue de Valombrose, Nice, France. wakkach@unice.fr
Augier
Séverine
S
Breittmayer
Jean-Philippe
JP
Blin-Wakkach
Claudine
C
Carle
Georges F
GF
D000818:Animals; D000951:Antigens, Neoplasm; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C484226:Atp6ap1 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; D025262:Vacuolar Proton-Translocating ATPases