Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response
To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was de...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2009-03, Vol.30 (3), p.458-469 |
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| creator | Zhang, Nan Schröppel, Bernd Lal, Girdhari Jakubzick, Claudia Mao, Xia Chen, Dan Yin, Na Jessberger, Rolf Ochando, Jordi C. Ding, Yaozhong Bromberg, Jonathan S. |
| description | To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-β and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function. |
| doi_str_mv | 10.1016/j.immuni.2008.12.022 |
| format | Article |
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Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-β and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2008.12.022</identifier><identifier>PMID: 19303390</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autoimmunity - immunology ; Cell adhesion & migration ; Cell Movement - immunology ; CELLIMMUNO ; Cells, Cultured ; Chemokines ; Dendritic Cells - immunology ; Dendritic Cells - physiology ; Fatty acids ; Immune system ; Inflammation ; Islets of Langerhans - cytology ; Islets of Langerhans - immunology ; Ligands ; Lymph Nodes - immunology ; Lymphocyte Subsets - immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Software ; Studies ; Survival analysis ; T cell receptors ; T-Lymphocytes, Regulatory - immunology ; Variance analysis</subject><ispartof>Immunity (Cambridge, Mass.), 2009-03, Vol.30 (3), p.458-469</ispartof><rights>2009 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Mar 20, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-c1bf564fa8cc952632e39e665f86d8094d69bc31b14859c0e9ee0885d6eb97003</citedby><cites>FETCH-LOGICAL-c465t-c1bf564fa8cc952632e39e665f86d8094d69bc31b14859c0e9ee0885d6eb97003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.immuni.2008.12.022$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19303390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Nan</creatorcontrib><creatorcontrib>Schröppel, Bernd</creatorcontrib><creatorcontrib>Lal, Girdhari</creatorcontrib><creatorcontrib>Jakubzick, Claudia</creatorcontrib><creatorcontrib>Mao, Xia</creatorcontrib><creatorcontrib>Chen, Dan</creatorcontrib><creatorcontrib>Yin, Na</creatorcontrib><creatorcontrib>Jessberger, Rolf</creatorcontrib><creatorcontrib>Ochando, Jordi C.</creatorcontrib><creatorcontrib>Ding, Yaozhong</creatorcontrib><creatorcontrib>Bromberg, Jonathan S.</creatorcontrib><title>Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. 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These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.</description><subject>Animals</subject><subject>Autoimmunity - immunology</subject><subject>Cell adhesion & migration</subject><subject>Cell Movement - immunology</subject><subject>CELLIMMUNO</subject><subject>Cells, Cultured</subject><subject>Chemokines</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - physiology</subject><subject>Fatty acids</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - immunology</subject><subject>Ligands</subject><subject>Lymph Nodes - immunology</subject><subject>Lymphocyte Subsets - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Software</subject><subject>Studies</subject><subject>Survival analysis</subject><subject>T cell receptors</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Variance analysis</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFr1TAUx4s43Jx-A5GA4Fu7kzZJkxdhXJ0O7iZs1-fQpqd3ubRNTVqh33659oLggz7lEH7nJP_zS5J3FDIKVFwdMtv382CzHEBmNM8gz18kFxRUmTIq4eWxLllaClqcJ69DOABQxhW8Ss6pKqAoFFwkywPu566anF_Ijmyw6wJ5xJ8zDpOtum4hd3bvqwlJ611Pboe2q3psyM6GMGMgkyOffWUHO-zJdunHJ3LvmvX-cR5HjyHWT0iuu879_i6SBwyjGwK-Sc7aqgv49nReJj9uvuw239Lt96-3m-ttapjgU2po3XLB2koao3guihwLhULwVopGgmKNULUpaE2Z5MoAKkSQkjcCa1UCFJfJx3Xu6F3MFSbd22Bi0GpANwctSmBKSvZfMAdWciFUBD_8BR7c7IcYQlMOLBcc6JFiK2W8C8Fjq0dv-8ovmoI-GtQHvRrUR4Oa5joajG3vT8PnOm76T9NJWQQ-rQDGpf2y6HUwFgeDjfVoJt04--8XngGmAK7h</recordid><startdate>20090320</startdate><enddate>20090320</enddate><creator>Zhang, Nan</creator><creator>Schröppel, Bernd</creator><creator>Lal, Girdhari</creator><creator>Jakubzick, Claudia</creator><creator>Mao, Xia</creator><creator>Chen, Dan</creator><creator>Yin, Na</creator><creator>Jessberger, Rolf</creator><creator>Ochando, Jordi C.</creator><creator>Ding, Yaozhong</creator><creator>Bromberg, Jonathan S.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20090320</creationdate><title>Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response</title><author>Zhang, Nan ; 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Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-β and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19303390</pmid><doi>10.1016/j.immuni.2008.12.022</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Autoimmunity - immunology Cell adhesion & migration Cell Movement - immunology CELLIMMUNO Cells, Cultured Chemokines Dendritic Cells - immunology Dendritic Cells - physiology Fatty acids Immune system Inflammation Islets of Langerhans - cytology Islets of Langerhans - immunology Ligands Lymph Nodes - immunology Lymphocyte Subsets - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Microscopy Reverse Transcriptase Polymerase Chain Reaction Rodents Software Studies Survival analysis T cell receptors T-Lymphocytes, Regulatory - immunology Variance analysis |
| title | Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response |
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