Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis
Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity...
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Veröffentlicht in: | The Journal of immunology (1950) 2005-06, Vol.174 (11), p.7141-7146 |
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container_title | The Journal of immunology (1950) |
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creator | Heuer, Josef G Zhang, Tonghai Zhao, Jingyong Ding, Chunjin Cramer, Martin Justen, Kathy L Vonderfecht, Steven L Na, Songqing |
description | Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity. In this study, we have used murine cecal ligation and puncture as a model of polymicrobial sepsis to explore the effects of adoptive transfer of Tregs on septic outcome. Adoptive transfer of in vitro-stimulated Tregs in both prevention and therapeutic modes significantly improved survival of cecal ligation and puncture mice. Furthermore, the effect was dependent on both the number of Tregs adoptively transferred and the presence of host T cells. Animals that received stimulated Tregs had significantly increased peritoneal mast cells and peritoneal TNF-alpha production. More importantly, adoptive transfer of in vitro-stimulated Tregs significantly improved bacterial clearance, which resulted in improved survival. Our results suggest a novel role for Tregs in sepsis. |
doi_str_mv | 10.4049/jimmunol.174.11.7141 |
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Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity. In this study, we have used murine cecal ligation and puncture as a model of polymicrobial sepsis to explore the effects of adoptive transfer of Tregs on septic outcome. Adoptive transfer of in vitro-stimulated Tregs in both prevention and therapeutic modes significantly improved survival of cecal ligation and puncture mice. Furthermore, the effect was dependent on both the number of Tregs adoptively transferred and the presence of host T cells. Animals that received stimulated Tregs had significantly increased peritoneal mast cells and peritoneal TNF-alpha production. More importantly, adoptive transfer of in vitro-stimulated Tregs significantly improved bacterial clearance, which resulted in improved survival. Our results suggest a novel role for Tregs in sepsis.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.174.11.7141</identifier><identifier>PMID: 15905557</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adoptive Transfer - methods ; Animals ; Cell Movement - immunology ; Cells, Cultured ; Dose-Response Relationship, Immunologic ; Female ; Injections, Intravenous ; Ligation ; Lymphocyte Activation - immunology ; Mast Cells - pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peritoneum - cytology ; Peritoneum - immunology ; Peritoneum - microbiology ; Punctures ; Receptors, Interleukin-2 - biosynthesis ; Sepsis - immunology ; Sepsis - microbiology ; Sepsis - mortality ; Sepsis - therapy ; Survival Analysis ; T-Lymphocytes, Regulatory - metabolism ; T-Lymphocytes, Regulatory - microbiology ; T-Lymphocytes, Regulatory - transplantation ; Tumor Necrosis Factor-alpha - biosynthesis</subject><ispartof>The Journal of immunology (1950), 2005-06, Vol.174 (11), p.7141-7146</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-80ead948d6649e5dac6f39a9a7582ec7798c8f0e2efbf7152bdff9dec0dd2f7e3</citedby><cites>FETCH-LOGICAL-c314t-80ead948d6649e5dac6f39a9a7582ec7798c8f0e2efbf7152bdff9dec0dd2f7e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15905557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heuer, Josef G</creatorcontrib><creatorcontrib>Zhang, Tonghai</creatorcontrib><creatorcontrib>Zhao, Jingyong</creatorcontrib><creatorcontrib>Ding, Chunjin</creatorcontrib><creatorcontrib>Cramer, Martin</creatorcontrib><creatorcontrib>Justen, Kathy L</creatorcontrib><creatorcontrib>Vonderfecht, Steven L</creatorcontrib><creatorcontrib>Na, Songqing</creatorcontrib><title>Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity. In this study, we have used murine cecal ligation and puncture as a model of polymicrobial sepsis to explore the effects of adoptive transfer of Tregs on septic outcome. Adoptive transfer of in vitro-stimulated Tregs in both prevention and therapeutic modes significantly improved survival of cecal ligation and puncture mice. Furthermore, the effect was dependent on both the number of Tregs adoptively transferred and the presence of host T cells. Animals that received stimulated Tregs had significantly increased peritoneal mast cells and peritoneal TNF-alpha production. More importantly, adoptive transfer of in vitro-stimulated Tregs significantly improved bacterial clearance, which resulted in improved survival. Our results suggest a novel role for Tregs in sepsis.</description><subject>Adoptive Transfer - methods</subject><subject>Animals</subject><subject>Cell Movement - immunology</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Female</subject><subject>Injections, Intravenous</subject><subject>Ligation</subject><subject>Lymphocyte Activation - immunology</subject><subject>Mast Cells - pathology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Peritoneum - cytology</subject><subject>Peritoneum - immunology</subject><subject>Peritoneum - microbiology</subject><subject>Punctures</subject><subject>Receptors, Interleukin-2 - biosynthesis</subject><subject>Sepsis - immunology</subject><subject>Sepsis - microbiology</subject><subject>Sepsis - mortality</subject><subject>Sepsis - therapy</subject><subject>Survival Analysis</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>T-Lymphocytes, Regulatory - microbiology</subject><subject>T-Lymphocytes, Regulatory - transplantation</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkd1uEzEQhS0EoqHwBgj5CiFVG-yNf9aXZQttpEogEri1HHvcuvLuBns3UR6DN8ZRguBqpJnvHM3MQegtJXNGmPr4FLpu6oc4p5LNKZ1LyugzNKOck0oIIp6jGSF1XVEp5AV6lfMTIUSQmr1EF5QrwjmXM_T72g3bMewAr5Pps4eEB4-XPf4ZxjRUqzF0UzQjONzesKv2puZX-Ds8HHtDOuA1biHGXAQ2gcmQ8SdjR0jBRNxGMMXTAja9w8tum4ZdAVZT2oVdmYcefxvioQs2DZujYAXbHPJr9MKbmOHNuV6iH18-r9u76v7r7bK9vq_sgrKxaggYp1jjhGAKuDNW-IUyykje1GClVI1tPIEa_MZLyuuN8145sMS52ktYXKL3J9-y168J8qi7kG25xvQwTFkL2fBaCVVAdgLLnjkn8HqbQmfSQVOij1Hov1HoEoWmVB-jKLJ3Z_9p04H7Jzr_vgAfTsBjeHjchwQ6dybGglO93-__9_oD7LWXsw</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Heuer, Josef G</creator><creator>Zhang, Tonghai</creator><creator>Zhao, Jingyong</creator><creator>Ding, Chunjin</creator><creator>Cramer, Martin</creator><creator>Justen, Kathy L</creator><creator>Vonderfecht, Steven L</creator><creator>Na, Songqing</creator><general>Am Assoc Immnol</general><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>7X8</scope></search><sort><creationdate>20050601</creationdate><title>Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis</title><author>Heuer, Josef G ; Zhang, Tonghai ; Zhao, Jingyong ; Ding, Chunjin ; Cramer, Martin ; Justen, Kathy L ; Vonderfecht, Steven L ; Na, Songqing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-80ead948d6649e5dac6f39a9a7582ec7798c8f0e2efbf7152bdff9dec0dd2f7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adoptive Transfer - methods</topic><topic>Animals</topic><topic>Cell Movement - immunology</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Female</topic><topic>Injections, Intravenous</topic><topic>Ligation</topic><topic>Lymphocyte Activation - immunology</topic><topic>Mast Cells - pathology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Peritoneum - cytology</topic><topic>Peritoneum - immunology</topic><topic>Peritoneum - microbiology</topic><topic>Punctures</topic><topic>Receptors, Interleukin-2 - biosynthesis</topic><topic>Sepsis - immunology</topic><topic>Sepsis - microbiology</topic><topic>Sepsis - mortality</topic><topic>Sepsis - therapy</topic><topic>Survival Analysis</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>T-Lymphocytes, Regulatory - microbiology</topic><topic>T-Lymphocytes, Regulatory - transplantation</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heuer, Josef G</creatorcontrib><creatorcontrib>Zhang, Tonghai</creatorcontrib><creatorcontrib>Zhao, Jingyong</creatorcontrib><creatorcontrib>Ding, Chunjin</creatorcontrib><creatorcontrib>Cramer, Martin</creatorcontrib><creatorcontrib>Justen, Kathy L</creatorcontrib><creatorcontrib>Vonderfecht, Steven L</creatorcontrib><creatorcontrib>Na, Songqing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heuer, Josef G</au><au>Zhang, Tonghai</au><au>Zhao, Jingyong</au><au>Ding, Chunjin</au><au>Cramer, Martin</au><au>Justen, Kathy L</au><au>Vonderfecht, Steven L</au><au>Na, Songqing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>174</volume><issue>11</issue><spage>7141</spage><epage>7146</epage><pages>7141-7146</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Regulatory CD4(+)CD25(+) T cells (Tregs) suppress autoimmune and inflammatory diseases through mechanisms that are only partly understood. Previous studies suggest that Tregs can suppress bacterially triggered intestinal inflammation and respond to LPS through TLRs with enhanced suppressive activity. In this study, we have used murine cecal ligation and puncture as a model of polymicrobial sepsis to explore the effects of adoptive transfer of Tregs on septic outcome. Adoptive transfer of in vitro-stimulated Tregs in both prevention and therapeutic modes significantly improved survival of cecal ligation and puncture mice. Furthermore, the effect was dependent on both the number of Tregs adoptively transferred and the presence of host T cells. Animals that received stimulated Tregs had significantly increased peritoneal mast cells and peritoneal TNF-alpha production. More importantly, adoptive transfer of in vitro-stimulated Tregs significantly improved bacterial clearance, which resulted in improved survival. Our results suggest a novel role for Tregs in sepsis.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>15905557</pmid><doi>10.4049/jimmunol.174.11.7141</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adoptive Transfer - methods Animals Cell Movement - immunology Cells, Cultured Dose-Response Relationship, Immunologic Female Injections, Intravenous Ligation Lymphocyte Activation - immunology Mast Cells - pathology Mice Mice, Inbred BALB C Mice, Nude Peritoneum - cytology Peritoneum - immunology Peritoneum - microbiology Punctures Receptors, Interleukin-2 - biosynthesis Sepsis - immunology Sepsis - microbiology Sepsis - mortality Sepsis - therapy Survival Analysis T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - microbiology T-Lymphocytes, Regulatory - transplantation Tumor Necrosis Factor-alpha - biosynthesis |
title | Adoptive Transfer of In Vitro-Stimulated CD4+CD25+ Regulatory T Cells Increases Bacterial Clearance and Improves Survival in Polymicrobial Sepsis |
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