Cooperation of Invariant NKT Cells and CD4+CD25+ T Regulatory Cells in the Prevention of Autoimmune Myasthenia
CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explore...
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| Veröffentlicht in: | The Journal of immunology (1950) 2005-12, Vol.175 (12), p.7898-7904 |
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| container_title | The Journal of immunology (1950) |
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| creator | Liu, Ruolan La Cava, Antonio Bai, Xue-Feng Jee, Youngheun Price, Mary Campagnolo, Denise I Christadoss, Premkumar Vollmer, Timothy L Van Kaer, Luc Shi, Fu-Dong |
| description | CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, alpha-galactosylceramide (alpha-GalCer), inhibits the development of EAMG. alpha-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4+CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, alpha-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of alpha-GalCer in this model. Thus, alpha-GalCer-activated NKT cells can induce expansion of CD4+CD25+ Treg cells, which in turn mediate the therapeutic effects of alpha-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease. |
| doi_str_mv | 10.4049/jimmunol.175.12.7898 |
| format | Article |
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Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, alpha-galactosylceramide (alpha-GalCer), inhibits the development of EAMG. alpha-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4+CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, alpha-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of alpha-GalCer in this model. Thus, alpha-GalCer-activated NKT cells can induce expansion of CD4+CD25+ Treg cells, which in turn mediate the therapeutic effects of alpha-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.175.12.7898</identifier><identifier>PMID: 16339525</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Animals ; CD4 Antigens - genetics ; Female ; Forkhead Transcription Factors - genetics ; Galactosylceramides - pharmacology ; Galactosylceramides - therapeutic use ; Interleukin-2 - biosynthesis ; Interleukin-2 - genetics ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - physiology ; Mice ; Mice, Knockout ; Myasthenia Gravis, Autoimmune, Experimental - drug therapy ; Myasthenia Gravis, Autoimmune, Experimental - immunology ; Receptors, Interleukin-2 ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - physiology ; Up-Regulation - drug effects</subject><ispartof>The Journal of immunology (1950), 2005-12, Vol.175 (12), p.7898-7904</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-c730984954be57d31077f6f1dde85b9076f324f20f25b03d11f8c6597e00b6cc3</citedby><cites>FETCH-LOGICAL-c314t-c730984954be57d31077f6f1dde85b9076f324f20f25b03d11f8c6597e00b6cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16339525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Ruolan</creatorcontrib><creatorcontrib>La Cava, Antonio</creatorcontrib><creatorcontrib>Bai, Xue-Feng</creatorcontrib><creatorcontrib>Jee, Youngheun</creatorcontrib><creatorcontrib>Price, Mary</creatorcontrib><creatorcontrib>Campagnolo, Denise I</creatorcontrib><creatorcontrib>Christadoss, Premkumar</creatorcontrib><creatorcontrib>Vollmer, Timothy L</creatorcontrib><creatorcontrib>Van Kaer, Luc</creatorcontrib><creatorcontrib>Shi, Fu-Dong</creatorcontrib><title>Cooperation of Invariant NKT Cells and CD4+CD25+ T Regulatory Cells in the Prevention of Autoimmune Myasthenia</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, alpha-galactosylceramide (alpha-GalCer), inhibits the development of EAMG. alpha-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4+CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, alpha-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of alpha-GalCer in this model. Thus, alpha-GalCer-activated NKT cells can induce expansion of CD4+CD25+ Treg cells, which in turn mediate the therapeutic effects of alpha-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease.</description><subject>Animals</subject><subject>CD4 Antigens - genetics</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Galactosylceramides - pharmacology</subject><subject>Galactosylceramides - therapeutic use</subject><subject>Interleukin-2 - biosynthesis</subject><subject>Interleukin-2 - genetics</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - physiology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - drug therapy</subject><subject>Myasthenia Gravis, Autoimmune, Experimental - immunology</subject><subject>Receptors, Interleukin-2</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - physiology</subject><subject>Up-Regulation - drug effects</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>eNpNkEtP3DAURq2qqExp_wFCXlWVUIZrx68sUegDFWhVTdeWk9iMUWJP7YTR_HtCZ1BZ3c25R58OQqcElgxYdfHgh2EKsV8SyZeELqWq1Bu0IJxDIQSIt2gBQGlBpJDH6H3ODwAggLJ36JiIsqw45QsU6hg3NpnRx4Cjw9fh0SRvwojvfqxwbfs-YxM6XF-x8_qK8nO8wr_t_dSbMabdAfABj2uLfyX7aMOL6XIa47-JFt_uTJ6B4M0HdORMn-3Hwz1Bf75-WdXfi5uf367ry5uiLQkbi1aWUClWcdZYLruSgJROONJ1VvGmAilcSZmj4ChvoOwIcaoVvJIWoBFtW56gT3vvJsW_k82jHnxu57Em2DhlLZRSnCg6g2wPtinmnKzTm-QHk3aagH7urF8667mzJlQ_d57fzg7-qRls9__pEHYGPu-Btb9fb32yOg-m72ec6O12-9r1BDPoiFE</recordid><startdate>20051215</startdate><enddate>20051215</enddate><creator>Liu, Ruolan</creator><creator>La Cava, Antonio</creator><creator>Bai, Xue-Feng</creator><creator>Jee, Youngheun</creator><creator>Price, Mary</creator><creator>Campagnolo, Denise I</creator><creator>Christadoss, Premkumar</creator><creator>Vollmer, Timothy L</creator><creator>Van Kaer, Luc</creator><creator>Shi, Fu-Dong</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>20051215</creationdate><title>Cooperation of Invariant NKT Cells and CD4+CD25+ T Regulatory Cells in the Prevention of Autoimmune Myasthenia</title><author>Liu, Ruolan ; La Cava, Antonio ; Bai, Xue-Feng ; Jee, Youngheun ; Price, Mary ; Campagnolo, Denise I ; Christadoss, Premkumar ; Vollmer, Timothy L ; Van Kaer, Luc ; Shi, Fu-Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-c730984954be57d31077f6f1dde85b9076f324f20f25b03d11f8c6597e00b6cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>CD4 Antigens - genetics</topic><topic>Female</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Galactosylceramides - pharmacology</topic><topic>Galactosylceramides - therapeutic use</topic><topic>Interleukin-2 - biosynthesis</topic><topic>Interleukin-2 - genetics</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Killer Cells, Natural - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - drug therapy</topic><topic>Myasthenia Gravis, Autoimmune, Experimental - immunology</topic><topic>Receptors, Interleukin-2</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - physiology</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Ruolan</creatorcontrib><creatorcontrib>La Cava, Antonio</creatorcontrib><creatorcontrib>Bai, Xue-Feng</creatorcontrib><creatorcontrib>Jee, Youngheun</creatorcontrib><creatorcontrib>Price, Mary</creatorcontrib><creatorcontrib>Campagnolo, Denise I</creatorcontrib><creatorcontrib>Christadoss, Premkumar</creatorcontrib><creatorcontrib>Vollmer, Timothy L</creatorcontrib><creatorcontrib>Van Kaer, Luc</creatorcontrib><creatorcontrib>Shi, Fu-Dong</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>Liu, Ruolan</au><au>La Cava, Antonio</au><au>Bai, Xue-Feng</au><au>Jee, Youngheun</au><au>Price, Mary</au><au>Campagnolo, Denise I</au><au>Christadoss, Premkumar</au><au>Vollmer, Timothy L</au><au>Van Kaer, Luc</au><au>Shi, Fu-Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cooperation of Invariant NKT Cells and CD4+CD25+ T Regulatory Cells in the Prevention of Autoimmune Myasthenia</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2005-12-15</date><risdate>2005</risdate><volume>175</volume><issue>12</issue><spage>7898</spage><epage>7904</epage><pages>7898-7904</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor. We have demonstrated that activation of NKT cells by a synthetic glycolipid agonist of NKT cells, alpha-galactosylceramide (alpha-GalCer), inhibits the development of EAMG. alpha-GalCer administration in EAMG mice increased the size of the Treg cell compartment, and augmented the expression of foxp3 and the potency of CD4+CD25+ cells to inhibit proliferation of autoreactive T cells. Furthermore, alpha-GalCer promoted NKT cells to transcribe the IL-2 gene and produce IL-2 protein. Depletion of CD25+ cells or neutralization of IL-2 reduced the therapeutic effect of alpha-GalCer in this model. Thus, alpha-GalCer-activated NKT cells can induce expansion of CD4+CD25+ Treg cells, which in turn mediate the therapeutic effects of alpha-GalCer in EAMG. Induced cooperation of NKT cells and Treg cells may serve as a superior strategy to treat autoimmune disease.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>16339525</pmid><doi>10.4049/jimmunol.175.12.7898</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of immunology (1950), 2005-12, Vol.175 (12), p.7898-7904 |
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| subjects | Animals CD4 Antigens - genetics Female Forkhead Transcription Factors - genetics Galactosylceramides - pharmacology Galactosylceramides - therapeutic use Interleukin-2 - biosynthesis Interleukin-2 - genetics Killer Cells, Natural - drug effects Killer Cells, Natural - physiology Mice Mice, Knockout Myasthenia Gravis, Autoimmune, Experimental - drug therapy Myasthenia Gravis, Autoimmune, Experimental - immunology Receptors, Interleukin-2 T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - physiology Up-Regulation - drug effects |
| title | Cooperation of Invariant NKT Cells and CD4+CD25+ T Regulatory Cells in the Prevention of Autoimmune Myasthenia |
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