High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells
Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applie...
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| Veröffentlicht in: | European journal of immunology 2011-11, Vol.41 (11), p.3101-3113 |
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| creator | Föhse, Lisa Suffner, Janine Suhre, Karsten Wahl, Benjamin Lindner, Cornelia Lee, Chun-Wei Schmitz, Susanne Haas, Jan D Lamprecht, Stella Koenecke, Christian Bleich, André Hämmerling, Günter J Malissen, Bernard Suerbaum, Sebastian Förster, Reinhold Prinz, Immo |
| description | Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire. |
| doi_str_mv | 10.1002/eji.201141986 |
| format | Article |
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However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. 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KGaA, Weinheim.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-7025-1735</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21932448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00672196$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Föhse, Lisa</creatorcontrib><creatorcontrib>Suffner, Janine</creatorcontrib><creatorcontrib>Suhre, Karsten</creatorcontrib><creatorcontrib>Wahl, Benjamin</creatorcontrib><creatorcontrib>Lindner, Cornelia</creatorcontrib><creatorcontrib>Lee, Chun-Wei</creatorcontrib><creatorcontrib>Schmitz, Susanne</creatorcontrib><creatorcontrib>Haas, Jan D</creatorcontrib><creatorcontrib>Lamprecht, Stella</creatorcontrib><creatorcontrib>Koenecke, Christian</creatorcontrib><creatorcontrib>Bleich, André</creatorcontrib><creatorcontrib>Hämmerling, Günter J</creatorcontrib><creatorcontrib>Malissen, Bernard</creatorcontrib><creatorcontrib>Suerbaum, Sebastian</creatorcontrib><creatorcontrib>Förster, Reinhold</creatorcontrib><creatorcontrib>Prinz, Immo</creatorcontrib><title>High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>Dominant tolerance to self-antigen requires the presence of sufficient numbers of CD4(+) Foxp3(+) Treg cells with matching antigen specificity. 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Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Cell Separation</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Graft vs Host Disease</subject><subject>Graft vs Host Disease - immunology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Homeostasis</subject><subject>Homeostasis - genetics</subject><subject>Homeostasis - immunology</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Receptors, Antigen, T-Cell</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Self Tolerance</subject><subject>Self Tolerance - genetics</subject><subject>Self Tolerance - immunology</subject><subject>T-Lymphocytes, Regulatory</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1Lw0AQhhdRbK0evcreRCR1ZrP52KMUa4WCIBW8hd3sptmSZGs2Kfbfm9LqaZjh4eGdl5BbhCkCsCezsVMGiBxFGp-RMUYMAz6s52QMgDxgIoURufJ-AwAijsQlGTEUIeM8HZOvhV2XdDX7oNruTOttt6em8X1rPHXbztayokXf5J11DZWNpqWrjfOd9HYACjp3P9vwkbZm3Veyc-2ermhuqspfk4tCVt7cnOaEfM5fVrNFsHx_fZs9L4MSE94FMQKPlBIhMCYKAJUnCsHoUAipIo251kor1JHgEbBEpalRKsIcCx2GClg4IQ9HbymrbNsOgdt95qTNFs_L7HADiJPh33iHA3t_ZLet--6N77La-kNa2RjX-0wMLGeQHqx3J7JXtdH_4r_iwl9vfW66</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Föhse, Lisa</creator><creator>Suffner, Janine</creator><creator>Suhre, Karsten</creator><creator>Wahl, Benjamin</creator><creator>Lindner, Cornelia</creator><creator>Lee, Chun-Wei</creator><creator>Schmitz, Susanne</creator><creator>Haas, Jan D</creator><creator>Lamprecht, Stella</creator><creator>Koenecke, Christian</creator><creator>Bleich, André</creator><creator>Hämmerling, Günter J</creator><creator>Malissen, Bernard</creator><creator>Suerbaum, Sebastian</creator><creator>Förster, Reinhold</creator><creator>Prinz, Immo</creator><general>Wiley-VCH Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-7025-1735</orcidid></search><sort><creationdate>201111</creationdate><title>High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells</title><author>Föhse, Lisa ; 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However, the size and role of TCR repertoire diversity for antigen-specific immuno-regulation through Treg cells is not clear. Here, we developed and applied a novel high-throughput (HT) TCR sequencing approach to analyze the TCR repertoire of Treg cells and revealed the importance of high diversity for Treg-cell homeostasis and function. We found that highly polyclonal Treg cells from WT mice vigorously expanded after adoptive transfer into non-lymphopenic TCR-transgenic recipients with low Treg-cell diversity. In that system, we identified specific Treg-cell TCR preferences in distinct anatomic locations such as the mesenteric LN indicating that Treg cells continuously compete for MHC class-II-presented self-, food-, or flora-antigen. Functionally, we showed that high TCR diversity was required for optimal suppressive function of Treg cells in experimental acute graft versus host disease (GvHD). In conclusion, we suggest that efficient immuno-regulation by Treg cells requires high TCR diversity. Thereby, continuous competition of peripheral Treg cells for limited self-antigen shapes an organ-optimized, yet highly diverse, local TCR repertoire.</abstract><cop>Germany</cop><pub>Wiley-VCH Verlag</pub><pmid>21932448</pmid><doi>10.1002/eji.201141986</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7025-1735</orcidid></addata></record> |
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| ispartof | European journal of immunology, 2011-11, Vol.41 (11), p.3101-3113 |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection) |
| subjects | Adoptive Transfer Animals Cell Separation Flow Cytometry Forkhead Transcription Factors Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology Graft vs Host Disease Graft vs Host Disease - immunology High-Throughput Nucleotide Sequencing High-Throughput Nucleotide Sequencing - methods Homeostasis Homeostasis - genetics Homeostasis - immunology Immunology Life Sciences Male Mice Mice, Inbred C57BL Mice, Transgenic Receptors, Antigen, T-Cell Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology Self Tolerance Self Tolerance - genetics Self Tolerance - immunology T-Lymphocytes, Regulatory T-Lymphocytes, Regulatory - immunology |
| title | High TCR diversity ensures optimal function and homeostasis of Foxp3+ regulatory T cells |
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