%0 Journal Article %T Continuous Activation of the CD122/STAT-5 Signaling Pathway during Selection of Antigen-Specific Regulatory T Cells in the Murine Thymus. %+ Immunologie - Immunopathologie - Immunothérapeutique (I3) %+ Becton Dickinson Technologies %A Goldstein, Jérémie, D. %A Balderas, Robert, S. %A Marodon, Gilles %Z This work was funded by the Agence Nationale de la Recherche (ANR), Agence Nationale de la Recherche contre le SIDA (ANRS), and the Association Francaise contre les Myopathies (AFM). J.D. Goldstein is a recipient of a Ph.D fellowship from the French Ministère de l'Enseignement Supérieur et de la Recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. %< avec comité de lecture %@ 1932-6203 %J PLoS ONE %I Public Library of Science %V 6 %N 4 %P e19038 %8 2011 %D 2011 %R 10.1371/journal.pone.0019038 %M 21541329 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X 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(+)CD8(-) subsets. In the neonatal thymus, the numbers of pSTAT-5(+) cells in CD25(+)foxp3(-) and nTreg cells increased in parallel, suggesting that pSTAT-5(+)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, STAT-5 activation upon IL-2 stimulation correlated better with foxp3 and CD122 than with CD25 expression. Finally, we show that expression of an endogenous superantigen strongly affected the early Treg cell repertoire but not the proportion of pSTAT-5(+) cells within this repertoire. Our results reveal that continuous activation of the CD122/STAT-5 signaling pathway characterize regulatory lineage differentiation in the murine thymus. %G English %2 https://inserm.hal.science/inserm-00595041/document %2 https://inserm.hal.science/inserm-00595041/file/PlosOne.pdf %L inserm-00595041 %U https://inserm.hal.science/inserm-00595041 %~ INSERM %~ UPMC %~ CNRS %~ I3 %~ UPMC_POLE_4 %~ SORBONNE-UNIVERSITE %~ SU-MEDECINE %~ SU-TI %~ ALLIANCE-SU