IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells
It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic a...
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| Veröffentlicht in: | International immunology 2006-06, Vol.18 (6), p.827-835 |
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| creator | Riou, Catherine Dumont, Alain R Yassine-Diab, Bader Haddad, Elias K Sekaly, Rafick-Pierre |
| description | It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation. |
| doi_str_mv | 10.1093/intimm/dxl019 |
| format | Article |
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Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation.</description><identifier>ISSN: 0953-8178</identifier><identifier>EISSN: 1460-2377</identifier><identifier>DOI: 10.1093/intimm/dxl019</identifier><identifier>PMID: 16611649</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>apoptosis ; CD8-Positive T-Lymphocytes - immunology ; Cell Death - drug effects ; Cell Death - immunology ; Cell Differentiation - drug effects ; Cell Differentiation - immunology ; Cell Survival - drug effects ; Cell Survival - immunology ; Cells, Cultured ; CTL ; cytokine ; Genes, bcl-2 - immunology ; Granzymes ; Humans ; Interleukin-2 - immunology ; Interleukin-2 - pharmacology ; Interleukin-4 - immunology ; Interleukin-4 - pharmacology ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Receptors, Antigen, T-Cell - immunology ; Receptors, Interleukin-2 - immunology ; Serine Endopeptidases - immunology ; T cell activation ; T cell differentiation ; Up-Regulation - drug effects ; Up-Regulation - immunology</subject><ispartof>International immunology, 2006-06, Vol.18 (6), p.827-835</ispartof><rights>Copyright Oxford University Press(England) Jun 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-a1ef0d1a399d78ef5303eb1253986d14798a0d9b2f3e6c255184924cf2b387713</citedby><cites>FETCH-LOGICAL-c409t-a1ef0d1a399d78ef5303eb1253986d14798a0d9b2f3e6c255184924cf2b387713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16611649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Riou, Catherine</creatorcontrib><creatorcontrib>Dumont, Alain R</creatorcontrib><creatorcontrib>Yassine-Diab, Bader</creatorcontrib><creatorcontrib>Haddad, Elias K</creatorcontrib><creatorcontrib>Sekaly, Rafick-Pierre</creatorcontrib><title>IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells</title><title>International immunology</title><addtitle>Int Immunol</addtitle><description>It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation.</description><subject>apoptosis</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - immunology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - immunology</subject><subject>Cells, Cultured</subject><subject>CTL</subject><subject>cytokine</subject><subject>Genes, bcl-2 - immunology</subject><subject>Granzymes</subject><subject>Humans</subject><subject>Interleukin-2 - immunology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Interleukin-4 - immunology</subject><subject>Interleukin-4 - pharmacology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Receptors, Interleukin-2 - immunology</subject><subject>Serine Endopeptidases - immunology</subject><subject>T cell activation</subject><subject>T cell differentiation</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - immunology</subject><issn>0953-8178</issn><issn>1460-2377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhi0EotvCkSuyOHBBoZ44ie0jLB9bdQUcikBcLMcea10SZ4mdfvx7sh-iEqeRZh49ejUvIS-AvQWm-HmIOfT9ubvrGKhHZAFVw4qSC_GYLJiqeSFByBNymtI1Y4yXij8lJ9A0AE2lFuT2Yl1UNETfTRgtJpo3SF3wHkeczSaHIVIT3X6fpmRxm0MbupDvaR6osTnc7KEiRDdZdNRi11GHJm_o4Olm6k2k0YQbpMsP8g292gPpGXniTZfw-XGeke-fPl4tV8X66-eL5bt1YSumcmEAPXNguFJOSPQ1ZxxbKGuuZOOgEkoa5lRbeo6NLesaZKXKyvqy5VII4Gfk9cG7HYc_E6as-5B2CUzEYUq6kWz-D7AZfPUfeD1MY5yzaVA1Y1LJHVQcIDsOKY3o9XYMvRnvNTC9q0Mf6tCHOmb-5VE6tT26B_r4_wdhSBnv_t3N-Fs3gotar37-0vUK3n_5dnmpf_C_SUyWxA</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Riou, Catherine</creator><creator>Dumont, Alain R</creator><creator>Yassine-Diab, Bader</creator><creator>Haddad, Elias K</creator><creator>Sekaly, Rafick-Pierre</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</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>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060601</creationdate><title>IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells</title><author>Riou, Catherine ; Dumont, Alain R ; Yassine-Diab, Bader ; Haddad, Elias K ; Sekaly, Rafick-Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-a1ef0d1a399d78ef5303eb1253986d14798a0d9b2f3e6c255184924cf2b387713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>apoptosis</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Death - drug effects</topic><topic>Cell Death - immunology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - immunology</topic><topic>Cells, Cultured</topic><topic>CTL</topic><topic>cytokine</topic><topic>Genes, bcl-2 - immunology</topic><topic>Granzymes</topic><topic>Humans</topic><topic>Interleukin-2 - immunology</topic><topic>Interleukin-2 - pharmacology</topic><topic>Interleukin-4 - immunology</topic><topic>Interleukin-4 - pharmacology</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocyte Activation - immunology</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>Receptors, Interleukin-2 - immunology</topic><topic>Serine Endopeptidases - immunology</topic><topic>T cell activation</topic><topic>T cell differentiation</topic><topic>Up-Regulation - drug effects</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riou, Catherine</creatorcontrib><creatorcontrib>Dumont, Alain R</creatorcontrib><creatorcontrib>Yassine-Diab, Bader</creatorcontrib><creatorcontrib>Haddad, Elias K</creatorcontrib><creatorcontrib>Sekaly, Rafick-Pierre</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riou, Catherine</au><au>Dumont, Alain R</au><au>Yassine-Diab, Bader</au><au>Haddad, Elias K</au><au>Sekaly, Rafick-Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells</atitle><jtitle>International immunology</jtitle><addtitle>Int Immunol</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>18</volume><issue>6</issue><spage>827</spage><epage>835</epage><pages>827-835</pages><issn>0953-8178</issn><eissn>1460-2377</eissn><abstract>It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>16611649</pmid><doi>10.1093/intimm/dxl019</doi><tpages>9</tpages></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | apoptosis CD8-Positive T-Lymphocytes - immunology Cell Death - drug effects Cell Death - immunology Cell Differentiation - drug effects Cell Differentiation - immunology Cell Survival - drug effects Cell Survival - immunology Cells, Cultured CTL cytokine Genes, bcl-2 - immunology Granzymes Humans Interleukin-2 - immunology Interleukin-2 - pharmacology Interleukin-4 - immunology Interleukin-4 - pharmacology Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Receptors, Antigen, T-Cell - immunology Receptors, Interleukin-2 - immunology Serine Endopeptidases - immunology T cell activation T cell differentiation Up-Regulation - drug effects Up-Regulation - immunology |
| title | IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells |
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