Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance
T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobuli...
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| Veröffentlicht in: | Nature immunology 2003-11, Vol.4 (11), p.1102-1110 |
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| container_title | Nature immunology |
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| creator | Kuchroo, Vijay K Sabatos, Catherine A Chakravarti, Sumone Cha, Eugene Schubart, Anna Sánchez-Fueyo, Alberto Zheng, Xin Xiao Coyle, Anthony J Strom, Terry B Freeman, Gordon J |
| description | T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance. |
| doi_str_mv | 10.1038/ni988 |
| format | Article |
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Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni988</identifier><identifier>PMID: 14556006</identifier><language>eng</language><publisher>United States: Nature Publishing Group</publisher><subject>Antibodies - genetics ; Antibodies - metabolism ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Division - immunology ; Cell Division - physiology ; Hepatitis A Virus Cellular Receptor 2 ; Immune response ; Immune System - immunology ; Immune Tolerance - immunology ; Immunization ; Ligands ; Protein Isoforms ; Receptors, Virus - genetics ; Receptors, Virus - metabolism ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Recombinant Fusion Proteins - metabolism ; Th1 Cells - immunology ; Th1 Cells - metabolism</subject><ispartof>Nature immunology, 2003-11, Vol.4 (11), p.1102-1110</ispartof><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-996a73aa68a3fc2c53832ed4c3b65c4413d1ee2f2545cc0aceded7b0798ef4613</citedby><cites>FETCH-LOGICAL-c393t-996a73aa68a3fc2c53832ed4c3b65c4413d1ee2f2545cc0aceded7b0798ef4613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14556006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuchroo, Vijay K</creatorcontrib><creatorcontrib>Sabatos, Catherine A</creatorcontrib><creatorcontrib>Chakravarti, Sumone</creatorcontrib><creatorcontrib>Cha, Eugene</creatorcontrib><creatorcontrib>Schubart, Anna</creatorcontrib><creatorcontrib>Sánchez-Fueyo, Alberto</creatorcontrib><creatorcontrib>Zheng, Xin Xiao</creatorcontrib><creatorcontrib>Coyle, Anthony J</creatorcontrib><creatorcontrib>Strom, Terry B</creatorcontrib><creatorcontrib>Freeman, Gordon J</creatorcontrib><title>Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><description>T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. 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Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuchroo, Vijay K</au><au>Sabatos, Catherine A</au><au>Chakravarti, Sumone</au><au>Cha, Eugene</au><au>Schubart, Anna</au><au>Sánchez-Fueyo, Alberto</au><au>Zheng, Xin Xiao</au><au>Coyle, Anthony J</au><au>Strom, Terry B</au><au>Freeman, Gordon J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance</atitle><jtitle>Nature immunology</jtitle><addtitle>Nat Immunol</addtitle><date>2003-11-01</date><risdate>2003</risdate><volume>4</volume><issue>11</issue><spage>1102</spage><epage>1110</epage><pages>1102-1110</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.</abstract><cop>United States</cop><pub>Nature Publishing Group</pub><pmid>14556006</pmid><doi>10.1038/ni988</doi><tpages>9</tpages></addata></record> |
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| subjects | Antibodies - genetics Antibodies - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Division - immunology Cell Division - physiology Hepatitis A Virus Cellular Receptor 2 Immune response Immune System - immunology Immune Tolerance - immunology Immunization Ligands Protein Isoforms Receptors, Virus - genetics Receptors, Virus - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - metabolism Th1 Cells - immunology Th1 Cells - metabolism |
| title | Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance |
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