Continuous Activation of the CD122/STAT-5 Signaling Pathway during Selection of Antigen-Specific Regulatory T Cells in the Murine Thymus
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{"title"=>"Continuous activation of the CD122/STAT-5 signaling pathway during selection of antigen-specific regulatory T cells in the murine thymus", "type"=>"journal", "authors"=>[{"first_name"=>"Jérémie D.", "last_name"=>"Goldstein", "scopus_author_id"=>"37031161900"}, {"first_name"=>"Robert S.", "last_name"=>"Balderas", "scopus_author_id"=>"56004080300"}, {"first_name"=>"Gilles", "last_name"=>"Marodon", "scopus_author_id"=>"6603474524"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"361702850", "scopus"=>"2-s2.0-79955613600", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "pmid"=>"21541329", "sgr"=>"79955613600", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0019038"}, "id"=>"2142c6eb-8f51-3f00-8fa5-a3bc2f1eaa95", "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(+)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.", "link"=>"http://www.mendeley.com/research/continuous-activation-cd122stat5-signaling-pathway-during-selection-antigenspecific-regulatory-t-cel", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>7, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"China"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/391262", "https://ndownloader.figshare.com/files/391298", "https://ndownloader.figshare.com/files/391326", "https://ndownloader.figshare.com/files/391351"], "description"=>"<div><p>Signaling events affecting thymic selection of un-manipulated polyclonal natural CD25<sup>+</sup>foxp3<sup>+</sup> regulatory T cells (nTreg) have not been established <em>ex vivo</em>. 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<sup>+</sup>CD8<sup>−</sup> subsets. In the neonatal thymus, the numbers of pSTAT-5<sup>+</sup> cells in CD25<sup>+</sup>foxp3<sup>−</sup> and nTreg cells increased in parallel, suggesting that pSTAT-5<sup>+</sup>CD25<sup>+</sup>foxp3<sup>−</sup> cells might represent the precursors of foxp3<sup>+</sup> regulatory T cells. This “specific” pSTAT-5 expression detected in nTreg cells <em>ex vivo</em> was likely due to a very recent signal given by IL-2/IL-15 cytokines <em>in vivo</em> since (i) it disappeared rapidly if cells were left unstimulated <em>in vitro</em> and (ii) was also observed if total thymocytes were stimulated <em>in vitro</em> 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<sup>+</sup> 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.</p> </div>", "links"=>[], "tags"=>["activation", "signaling", "pathway", "antigen-specific", "cells", "murine", "thymus"], "article_id"=>137271, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.s001", "https://dx.doi.org/10.1371/journal.pone.0019038.s002", "https://dx.doi.org/10.1371/journal.pone.0019038.s003", "https://dx.doi.org/10.1371/journal.pone.0019038.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Continuous_Activation_of_the_CD122_STAT_5_Signaling_Pathway_during_Selection_of_Antigen_Specific_Regulatory_T_Cells_in_the_Murine_Thymus/137271", "title"=>"Continuous Activation of the CD122/STAT-5 Signaling Pathway during Selection of Antigen-Specific Regulatory T Cells in the Murine Thymus", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-04-26 02:01:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/780199"], "description"=>"<p>(<b>A</b>) The gating strategy is indicated by the arrows. <i>Left panel</i>: total thymocytes were stained with CD4 and CD8 antibodies. The indicated gate defines CD4<sup>+</sup>CD8<sup>−</sup> cells. <i>Middle panel</i>: CD25 and foxp3 expression in CD4<sup>+</sup>CD8<sup>−</sup> cells. <i>Right panel</i>: pSTAT-5 expression in CD25<sup>+</sup>foxp3<sup>+</sup>CD4<sup>+</sup>CD8<sup>−</sup> cells. (<b>B–C</b>) Frequencies of pSTAT-5<sup>+</sup> cells within thymic CD4<sup>+</sup>CD8<sup>−</sup> cells of the indicated CD25/foxp3 phenotype in the thymus (<b>B</b>) and in the mesenteric lymph nodes (<b>C</b>) in 6- to 13- week-old mice. Each dot represents a single mouse. Results are compiled from 4 to 11 independent experiments. The p values are indicated in each panel (***p<0.001; *p<0.05; NS not significant).</p>", "links"=>[], "tags"=>["phosphorylation", "stat-5", "cells"], "article_id"=>450569, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Preferential_phosphorylation_of_STAT_5_in_foxp3_cells_in_adult_C57BL_6_mice_/450569", "title"=>"Preferential phosphorylation of STAT-5 in foxp3<sup>+</sup> cells in adult C57BL/6 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-26 00:09:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/780268"], "description"=>"<p>(<b>A–B</b>) Frequencies (<b>A</b>) and absolute numbers (<b>B</b>) of CD4<sup>+</sup>CD8<sup>−</sup> cells of the indicated phenotype defined by CD25 and foxp3 expression in the thymus of C57BL/6 neonates at the indicated days after birth. For sake of clarity, analysis of CD25<sup>−</sup>foxp3<sup>−</sup> cells which encompass >90% of all CD4<sup>+</sup> T cells, is not included in the figure (<b>C–D</b>) Frequencies (<b>C</b>) and absolute numbers (<b>D</b>) of pSTAT-5<sup>+</sup> cells within CD4<sup>+</sup>CD8<sup>−</sup> thymic subsets defined by CD25 and foxp3 expression in C57BL/6 neonates at the indicated days after birth. The p values are indicated in each panel (***p<0.001; **p<0.01; *p<0.05; NS not significant). Results shown are the compilation of 2 independent experiments with 6 to 8 mice analyzed per day. For sake of clarity, only the p values comparing CD25<sup>+</sup>foxp3<sup>−</sup> and CD25<sup>+</sup>foxp3<sup>+</sup> cells are shown.</p>", "links"=>[], "tags"=>["pstat-5", "treg", "differentiation", "neonatal", "thymus"], "article_id"=>450638, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinetics_of_pSTAT_5_expression_during_Treg_cell_differentiation_in_the_neonatal_thymus_of_C57BL_6_mice_/450638", "title"=>"Kinetics of pSTAT-5 expression during Treg cell differentiation in the neonatal thymus of C57BL/6 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-26 00:10:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/780395"], "description"=>"<p>(<b>A</b>) Frequency of pSTAT-5<sup>+</sup> cells in CD25<sup>+</sup>foxp3<sup>+</sup>CD4<sup>+</sup>CD8<sup>−</sup> cells of the thymus and of the mesenteric lymph node (mLN) fixed with formaldehyde immediately after sacrifice (0 min.) or after 60 minute incubation on ice (60 min.). (<b>B</b>) Frequency of pSTAT-5<sup>+</sup> cells in thymocytes of the indicated CD25/foxp3 phenotype after <i>in vitro</i> incubation with the indicated cytokines for 60 min. (Med; medium only). Results shown are compiled from 2 to 8 independent experiments. (<b>C</b>) Representative profile of CD122 expression in the indicated thymic subsets defined by CD25 and foxp3 expression. Note the higher expression of CD122 in foxp3<sup>+</sup> cells (<b>D</b>) Median fluorescence intensity of CD122 expression in thymic subsets defined by CD25 and foxp3 expression. Each dot represents a single mouse. Results shown are compiled from 2 independent experiments. The p values are indicated in the figure (***p<0.001; **p<0.01).</p>", "links"=>[], "tags"=>["stat-5", "phosphorylation", "thymocytes", "correlates", "cd122"], "article_id"=>450765, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Preferential_STAT_5_phosphorylation_in_foxp3_thymocytes_in_vitro_correlates_with_CD122_expression_/450765", "title"=>"Preferential STAT-5 phosphorylation in foxp3<sup><b>+</b></sup> thymocytes <i>in vitro</i> correlates with CD122 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-26 00:12:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/780471"], "description"=>"<p>(<b>A</b>) Representative flow cytometry analysis of CD25 and foxp3 expression in BV6<sup>+</sup> or BV6<sup>−</sup> cells among CD4<sup>+</sup>CD8<sup>−</sup> thymocytes of a F1 mouse at day 3 after birth. (<b>B–E</b>) Frequencies and absolute numbers of CD25<sup>+</sup>foxp3<sup>+</sup> (<b>B–C</b>) or CD25<sup>+</sup>foxp3<sup>−</sup> cells (<b>D–E</b>) were determined in CD4<sup>+</sup>CD8<sup>−</sup> cells within the indicated TCR-expressing cells (BV6, BV11, BV8.1/8.2) from 3 to 21 mice at the indicated age after birth in B6D2 mice. Results shown are compiled from 17 independent experiments.</p>", "links"=>[], "tags"=>["cells", "lineage", "thymus", "f1"], "article_id"=>450846, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Enhanced_selection_of_Mls_1_a_8211_specific_T_cells_into_the_regulatory_lineage_in_the_thymus_of_C57BL_6_215_DBA_2_F1_neonates_/450846", "title"=>"Enhanced selection of Mls-1<sup>a</sup>–specific T cells into the regulatory lineage in the thymus of C57BL/6<b>×</b>DBA/2 F1 neonates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-26 00:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/780609"], "description"=>"a)<p>Results shown are the percentages of pSTAT-5<sup>+</sup> cells in BV6<sup>+</sup> and BV6<sup>−</sup> CD4<sup>+</sup>CD8<sup>−</sup> cells (rows) within cells of the indicated phenotype (columns) in the thymus of C57BL/6×DBA/2 mice at day 3 after birth. Results are compiled from 2 independent experiments from 6 mice.</p>", "links"=>[], "tags"=>["ntreg", "enriched"], "article_id"=>450985, "categories"=>["Physiology", "Molecular Biology", "Immunology"], "users"=>["Jérémie D. Goldstein", "Robert S. Balderas", "Gilles Marodon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019038.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Self_specific_nTreg_are_not_enriched_in_pSTAT_5_cells_a_/450985", "title"=>"Self-specific nTreg are not enriched in pSTAT-5<sup>+</sup> cells<sup>a)</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-26 00:16:25"}

PMC Usage Stats | Further Information

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Relative Metric

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