continuous activation of the cd122stat-5 signaling pathway during selection of antigen-specific regulatory t cells in the murine thymus连续cd122stat-5信号通路的激活在选择抗原调节性t细胞的小鼠胸腺.pdf

Continuous Activation of the CD122/STAT-5 Signaling Pathway during Selection of Antigen-Specific Regulatory T Cells in the Murine Thymus ´ ´ 1,2,3 4 1,2,3 Jeremie D. Goldstein , Robert S. Balderas , Gilles Marodon * ´ 1 UPMC Universite Paris 06, UMR 7211, Paris, France, 2 CNRS, UMR 7211, Paris, France, 3 INSERM, U959, Paris, France, 4 Becton Dickinson, San Diego, California, United States of America Abstract + + Signaling events affecting thymic selection of un-manipulated polyclonal natural CD25 foxp3 regulatory T cells (nTreg) have not been established ex vivo. Here, we report a higher frequency of phosphorylated STAT-5 (pSTAT-5) in nTreg cells in the adult murine thymus and to a lesser extent in the periphery, compared to other CD4+CD82 subsets. In the neonatal thymus, the numbers of pSTAT-5+ + 2 cells in CD25 foxp3 and nTreg cells increased in parallel, suggesting that pSTAT- 5+ + 2 + CD25 foxp3 cells might represent the precursors of foxp3 regulatory T cells. This ‘‘specific’’ pSTAT-5 expression detected in nTreg cells ex vivo was likely due to a very recent signal given by IL-2/IL-15 cytokines in vivo since (i) it disappeared rapidly if cells were left unstimulated in vitro and (ii) was also observed if total thymocytes were stimulated in vitro with saturating amounts of IL-2 and/or IL-15 but not IL-7. Interestingly, S