Comparison of stable human Treg and Th clones by transcriptional profiling
From cancerous and non-cancerous patients, we derived stable clones of CD4⁺ Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4⁺ cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas i...
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| Veröffentlicht in: | European journal of immunology 2009-03, Vol.39 (3), p.869-882 |
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| container_title | European journal of immunology |
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| creator | Stockis, Julie Fink, Wolfram François, Violaine Connerotte, Thierry de Smet, Charles Knoops, Laurent van der Bruggen, Pierre Boon, Thierry Coulie, Pierre G Lucas, Sophie |
| description | From cancerous and non-cancerous patients, we derived stable clones of CD4⁺ Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4⁺ cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-β signature. Both activated Treg and Th clones produced the latent form of TGF-β. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-β. A TGF-β signature was also displayed by a Th clone "suppressed" by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-β which has autocrine actions on Tregs and can have paracrine actions on other T cells. |
| doi_str_mv | 10.1002/eji.200838807 |
| format | Article |
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A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-β signature. Both activated Treg and Th clones produced the latent form of TGF-β. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-β. A TGF-β signature was also displayed by a Th clone "suppressed" by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-β which has autocrine actions on Tregs and can have paracrine actions on other T cells.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200838807</identifier><identifier>PMID: 19224638</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH Verlag</publisher><subject>Clone Cells - immunology ; Clone Cells - metabolism ; DNA Methylation - genetics ; DNA Methylation - immunology ; Female ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - immunology ; Forkhead Transcription Factors - metabolism ; Gene Expression Profiling ; Human T‐cell clones ; Humans ; Lymphocyte Activation - genetics ; Lymphocyte Activation - immunology ; Male ; Melanoma - immunology ; Melanoma - metabolism ; Skin Neoplasms - immunology ; Skin Neoplasms - metabolism ; Smad2 Protein - immunology ; Smad2 Protein - metabolism ; T-Lymphocytes, Helper-Inducer - immunology ; T-Lymphocytes, Helper-Inducer - metabolism ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; TGF‐β ; Transforming Growth Factor beta - immunology ; Transforming Growth Factor beta - metabolism ; Treg</subject><ispartof>European journal of immunology, 2009-03, Vol.39 (3), p.869-882</ispartof><rights>Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. 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A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-β signature. Both activated Treg and Th clones produced the latent form of TGF-β. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-β. A TGF-β signature was also displayed by a Th clone "suppressed" by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-β which has autocrine actions on Tregs and can have paracrine actions on other T cells.</description><subject>Clone Cells - immunology</subject><subject>Clone Cells - metabolism</subject><subject>DNA Methylation - genetics</subject><subject>DNA Methylation - immunology</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene Expression Profiling</subject><subject>Human T‐cell clones</subject><subject>Humans</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Male</subject><subject>Melanoma - immunology</subject><subject>Melanoma - metabolism</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - metabolism</subject><subject>Smad2 Protein - immunology</subject><subject>Smad2 Protein - metabolism</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><subject>T-Lymphocytes, Helper-Inducer - metabolism</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>TGF‐β</subject><subject>Transforming Growth Factor beta - immunology</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Treg</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kT1PIzEQQC3ECcJHSQuuTjQbZuz12i5RlONAka64UFveXTsY7a6DnQjl37OnRHAVlZvnN6M3hFwhTBGA3bnXMGUAiisF8ohMUDAsSizxmEwAsCyYVnBKznJ-BQBdCX1CTlEzVlZcTcjTLPZrm0KOA42e5o2tO0dftr0d6DK5FbVDS5cvtOni4DKtd3ST7JCbFNabEAfb0XWKPnRhWF2QH9522V0e3nPy_Gu-nP0uFn8eHmf3i6IRgLJQqGQla3Tco0TRamY1azh3TnHpVdtKBtorVtfWu3ZcmMu64U0pPPcCBOPn5OfeO05-27q8MX3Ijes6O7i4zaaSwHWlyxG8_RZEpVEJkBUf0WKPNinmnJw36xR6m3YGwfzrbMbO5rPzyF8f1Nu6d-0XfQg7AnIPvIfO7b63mfnT4__qm_1Pb6Oxq_E05vkvA-SAFWgmSv4B8cKRJA</recordid><startdate>200903</startdate><enddate>200903</enddate><creator>Stockis, Julie</creator><creator>Fink, Wolfram</creator><creator>François, Violaine</creator><creator>Connerotte, Thierry</creator><creator>de Smet, Charles</creator><creator>Knoops, Laurent</creator><creator>van der Bruggen, Pierre</creator><creator>Boon, Thierry</creator><creator>Coulie, Pierre G</creator><creator>Lucas, Sophie</creator><general>Wiley-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200903</creationdate><title>Comparison of stable human Treg and Th clones by transcriptional profiling</title><author>Stockis, Julie ; Fink, Wolfram ; François, Violaine ; Connerotte, Thierry ; de Smet, Charles ; Knoops, Laurent ; van der Bruggen, Pierre ; Boon, Thierry ; Coulie, Pierre G ; Lucas, Sophie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5017-818767b1e3f1715d92a92c33ee837f8dd7209f82bbafed96537bc3c45f3f50523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Clone Cells - immunology</topic><topic>Clone Cells - metabolism</topic><topic>DNA Methylation - genetics</topic><topic>DNA Methylation - immunology</topic><topic>Female</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - immunology</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gene Expression Profiling</topic><topic>Human T‐cell clones</topic><topic>Humans</topic><topic>Lymphocyte Activation - genetics</topic><topic>Lymphocyte Activation - immunology</topic><topic>Male</topic><topic>Melanoma - immunology</topic><topic>Melanoma - metabolism</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - metabolism</topic><topic>Smad2 Protein - immunology</topic><topic>Smad2 Protein - metabolism</topic><topic>T-Lymphocytes, Helper-Inducer - immunology</topic><topic>T-Lymphocytes, Helper-Inducer - metabolism</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>TGF‐β</topic><topic>Transforming Growth Factor beta - immunology</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Treg</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stockis, Julie</creatorcontrib><creatorcontrib>Fink, Wolfram</creatorcontrib><creatorcontrib>François, Violaine</creatorcontrib><creatorcontrib>Connerotte, Thierry</creatorcontrib><creatorcontrib>de Smet, Charles</creatorcontrib><creatorcontrib>Knoops, Laurent</creatorcontrib><creatorcontrib>van der Bruggen, Pierre</creatorcontrib><creatorcontrib>Boon, Thierry</creatorcontrib><creatorcontrib>Coulie, Pierre G</creatorcontrib><creatorcontrib>Lucas, Sophie</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stockis, Julie</au><au>Fink, Wolfram</au><au>François, Violaine</au><au>Connerotte, Thierry</au><au>de Smet, Charles</au><au>Knoops, Laurent</au><au>van der Bruggen, Pierre</au><au>Boon, Thierry</au><au>Coulie, Pierre G</au><au>Lucas, Sophie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of stable human Treg and Th clones by transcriptional profiling</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2009-03</date><risdate>2009</risdate><volume>39</volume><issue>3</issue><spage>869</spage><epage>882</epage><pages>869-882</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>From cancerous and non-cancerous patients, we derived stable clones of CD4⁺ Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4⁺ cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-β signature. Both activated Treg and Th clones produced the latent form of TGF-β. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-β. A TGF-β signature was also displayed by a Th clone "suppressed" by a Treg clone. 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| ispartof | European journal of immunology, 2009-03, Vol.39 (3), p.869-882 |
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| subjects | Clone Cells - immunology Clone Cells - metabolism DNA Methylation - genetics DNA Methylation - immunology Female Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology Forkhead Transcription Factors - metabolism Gene Expression Profiling Human T‐cell clones Humans Lymphocyte Activation - genetics Lymphocyte Activation - immunology Male Melanoma - immunology Melanoma - metabolism Skin Neoplasms - immunology Skin Neoplasms - metabolism Smad2 Protein - immunology Smad2 Protein - metabolism T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - metabolism T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism TGF‐β Transforming Growth Factor beta - immunology Transforming Growth Factor beta - metabolism Treg |
| title | Comparison of stable human Treg and Th clones by transcriptional profiling |
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