The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells
The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B...
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| Veröffentlicht in: | European journal of immunology 2003-04, Vol.33 (4), p.970-979 |
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| container_title | European journal of immunology |
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| creator | Workman, Creg J. Vignali, Dario A. A. |
| description | The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells. |
| doi_str_mv | 10.1002/eji.200323382 |
| format | Article |
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We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. 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A.</creatorcontrib><title>The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells.</description><subject>Activation</subject><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antigens, CD</subject><subject>CD223</subject><subject>CD4 Antigens - chemistry</subject><subject>Cell Death</subject><subject>Enterotoxins - pharmacology</subject><subject>Genes, T-Cell Receptor</subject><subject>Humans</subject><subject>LAG3 gene</subject><subject>LAG‐3</subject><subject>Lymphocyte Activation</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Mouse</subject><subject>Mutation</subject><subject>Sequence Alignment</subject><subject>T cell</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkLFOwzAURS0EoqUwsiJPCKSm2M9xHI9VWkpRJZYyMEVx8gJBSVPiBOjGJ_CNfAkpregG05Oezr26OoSccjbgjMEVPmcDYEyAED7skS6XwB2Xu3yfdBnjrgPaZx1yZO0zY0x7Uh-SDgdPAfNElzzMn5AGI_fr47PCPKoxoUWZY9zk2Kez4aT9C3oRjADEZZ9W-NisIUvrNobvy2hhs3JBy5RGcZ29_uTnNMY8t8fkII1yiyfb2yP31-N5cOPM7ibTYDhzYpcpcLTxjPHbYR5oKUzqxSpR3ICXSJm40o983xM6SXmKBtDVmmkVARfKBZOAFqJHzje9y6p8adDWYZHZ9YJogWVjQyW4lK2Pf0GuuWIAqgWdDRhXpbUVpuGyyoqoWoWchWvpYSs9_JXe8mfb4sYUmOzoreUWUBvgLctx9XdbOL6d7qq_AWAOiwg</recordid><startdate>200304</startdate><enddate>200304</enddate><creator>Workman, Creg J.</creator><creator>Vignali, Dario A. A.</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>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200304</creationdate><title>The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells</title><author>Workman, Creg J. ; Vignali, Dario A. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4072-9b6bb809662953bf6c7d71b26d55d458a88639df1feb2e499097a213742bd2933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Activation</topic><topic>Amino Acid Motifs</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antigens, CD</topic><topic>CD223</topic><topic>CD4 Antigens - chemistry</topic><topic>Cell Death</topic><topic>Enterotoxins - pharmacology</topic><topic>Genes, T-Cell Receptor</topic><topic>Humans</topic><topic>LAG3 gene</topic><topic>LAG‐3</topic><topic>Lymphocyte Activation</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Mouse</topic><topic>Mutation</topic><topic>Sequence Alignment</topic><topic>T cell</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Workman, Creg J.</creatorcontrib><creatorcontrib>Vignali, Dario A. 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A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2003-04</date><risdate>2003</risdate><volume>33</volume><issue>4</issue><spage>970</spage><epage>979</epage><pages>970-979</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag</pub><pmid>12672063</pmid><doi>10.1002/eji.200323382</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of immunology, 2003-04, Vol.33 (4), p.970-979 |
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| subjects | Activation Amino Acid Motifs Amino Acid Sequence Animals Antigens, CD CD223 CD4 Antigens - chemistry Cell Death Enterotoxins - pharmacology Genes, T-Cell Receptor Humans LAG3 gene LAG‐3 Lymphocyte Activation Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Knockout Mice, Transgenic Molecular Sequence Data Mouse Mutation Sequence Alignment T cell T-Lymphocytes - drug effects T-Lymphocytes - immunology |
| title | The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells |
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