The role of the common cytokine receptor gamma-chain in regulating IL-2-dependent, activation-induced CD8+ T cell death
IL-2-dependent, activation-induced T cell death (AICD) plays an important role in peripheral tolerance. Using CD8+ TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8+ T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells...
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| Veröffentlicht in: | The Journal of immunology (1950) 1999-09, Vol.163 (6), p.3131-3137 |
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| container_title | The Journal of immunology (1950) |
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| creator | Dai, Z Arakelov, A Wagener, M Konieczny, B T Lakkis, F G |
| description | IL-2-dependent, activation-induced T cell death (AICD) plays an important role in peripheral tolerance. Using CD8+ TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8+ T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells. Neutralizing IL-2, IL-2R alpha, or IL-2R beta inhibited AICD. In contrast, blocking the common cytokine receptor gamma-chain (gamma c) prevented Bcl-2 induction and augmented AICD. IL-2 up-regulated Fas ligand (FasL) and down-regulated gamma c expression on activated 2C cells in vitro and in vivo. Adult IL-2 gene-knockout mice displayed exaggerated gamma c expression on their CD8+, but not on their CD4+, T cells. IL-4, IL-7, and IL-15, which do not promote AICD, did not influence FasL or gamma c expression. These data provide evidence that IL-2 prepares CD8+ T lymphocytes for AICD by at least two mechanisms: 1) by up-regulating a pro-apoptotic molecule, FasL, and 2) by down-regulating a survival molecule, gamma c. |
| doi_str_mv | 10.4049/jimmunol.163.6.3131 |
| format | Article |
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Using CD8+ TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8+ T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells. Neutralizing IL-2, IL-2R alpha, or IL-2R beta inhibited AICD. In contrast, blocking the common cytokine receptor gamma-chain (gamma c) prevented Bcl-2 induction and augmented AICD. IL-2 up-regulated Fas ligand (FasL) and down-regulated gamma c expression on activated 2C cells in vitro and in vivo. Adult IL-2 gene-knockout mice displayed exaggerated gamma c expression on their CD8+, but not on their CD4+, T cells. IL-4, IL-7, and IL-15, which do not promote AICD, did not influence FasL or gamma c expression. 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Using CD8+ TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8+ T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells. Neutralizing IL-2, IL-2R alpha, or IL-2R beta inhibited AICD. In contrast, blocking the common cytokine receptor gamma-chain (gamma c) prevented Bcl-2 induction and augmented AICD. IL-2 up-regulated Fas ligand (FasL) and down-regulated gamma c expression on activated 2C cells in vitro and in vivo. Adult IL-2 gene-knockout mice displayed exaggerated gamma c expression on their CD8+, but not on their CD4+, T cells. IL-4, IL-7, and IL-15, which do not promote AICD, did not influence FasL or gamma c expression. These data provide evidence that IL-2 prepares CD8+ T lymphocytes for AICD by at least two mechanisms: 1) by up-regulating a pro-apoptotic molecule, FasL, and 2) by down-regulating a survival molecule, gamma c.</description><subject>AIDS/HIV</subject><subject>Animals</subject><subject>Antibodies, Blocking - pharmacology</subject><subject>Apoptosis - immunology</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cells, Cultured</subject><subject>Down-Regulation - immunology</subject><subject>Fas Ligand Protein</subject><subject>fas Receptor - metabolism</subject><subject>Interleukin-2 - physiology</subject><subject>Ligands</subject><subject>Lymphocyte Activation - immunology</subject><subject>Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</subject><subject>Receptors, Cytokine - antagonists & inhibitors</subject><subject>Receptors, Cytokine - biosynthesis</subject><subject>Receptors, Cytokine - immunology</subject><subject>Receptors, Cytokine - physiology</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Up-Regulation - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkFtLwzAUx4Mobl4-gSB58kVTc2vaPsq8wsCX-Ryy5HTrbJLZporf3o4pCAfOgf-Fww-hC0YzSWV1u2m8H0JsM6ZEpjLBBDtAU5bnlChF1SGaUso5YYUqJuik7zeUUkW5PEYTRmVR5EU1RV-LNeAutoBjjdN42-h9DNh-p_jehFEDC9sUO7wy3hti16YJeJwOVkNrUhNW-GVOOHGwheAgpBtsbGo-RykG0gQ3WHB4dl9e4wW20LbYgUnrM3RUm7aH8999it4eHxazZzJ_fXqZ3c2JFVIlYmBJy9JUYFXOnVXAmHNMMlMbWVZCcbGsa8nrsnaWcyMlFa4smCtHWdkqF6foat-77eLHAH3Svul3b5gAceh1sWPEVTEaxd5ou9j3HdR62zXedN-aUb3jrf9465G3VnrHe0xd_tYPSw_uX2YPWPwAFOZ-yA</recordid><startdate>19990915</startdate><enddate>19990915</enddate><creator>Dai, Z</creator><creator>Arakelov, A</creator><creator>Wagener, M</creator><creator>Konieczny, B T</creator><creator>Lakkis, F G</creator><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>19990915</creationdate><title>The role of the common cytokine receptor gamma-chain in regulating IL-2-dependent, activation-induced CD8+ T cell death</title><author>Dai, Z ; Arakelov, A ; Wagener, M ; Konieczny, B T ; Lakkis, F G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c346t-aeb088a9ec652dc6e11dd141afa4893623bff42f8fdc22a4403d871d8a486c953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>AIDS/HIV</topic><topic>Animals</topic><topic>Antibodies, Blocking - pharmacology</topic><topic>Apoptosis - immunology</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cells, Cultured</topic><topic>Down-Regulation - immunology</topic><topic>Fas Ligand Protein</topic><topic>fas Receptor - metabolism</topic><topic>Interleukin-2 - physiology</topic><topic>Ligands</topic><topic>Lymphocyte Activation - immunology</topic><topic>Membrane Glycoproteins - antagonists & inhibitors</topic><topic>Membrane Glycoproteins - biosynthesis</topic><topic>Membrane Glycoproteins - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-bcl-2 - biosynthesis</topic><topic>Receptors, Cytokine - antagonists & inhibitors</topic><topic>Receptors, Cytokine - biosynthesis</topic><topic>Receptors, Cytokine - immunology</topic><topic>Receptors, Cytokine - physiology</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dai, Z</creatorcontrib><creatorcontrib>Arakelov, A</creatorcontrib><creatorcontrib>Wagener, M</creatorcontrib><creatorcontrib>Konieczny, B T</creatorcontrib><creatorcontrib>Lakkis, F G</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>Dai, Z</au><au>Arakelov, A</au><au>Wagener, M</au><au>Konieczny, B T</au><au>Lakkis, F G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of the common cytokine receptor gamma-chain in regulating IL-2-dependent, activation-induced CD8+ T cell death</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1999-09-15</date><risdate>1999</risdate><volume>163</volume><issue>6</issue><spage>3131</spage><epage>3137</epage><pages>3131-3137</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>IL-2-dependent, activation-induced T cell death (AICD) plays an important role in peripheral tolerance. Using CD8+ TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8+ T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells. Neutralizing IL-2, IL-2R alpha, or IL-2R beta inhibited AICD. In contrast, blocking the common cytokine receptor gamma-chain (gamma c) prevented Bcl-2 induction and augmented AICD. IL-2 up-regulated Fas ligand (FasL) and down-regulated gamma c expression on activated 2C cells in vitro and in vivo. Adult IL-2 gene-knockout mice displayed exaggerated gamma c expression on their CD8+, but not on their CD4+, T cells. IL-4, IL-7, and IL-15, which do not promote AICD, did not influence FasL or gamma c expression. These data provide evidence that IL-2 prepares CD8+ T lymphocytes for AICD by at least two mechanisms: 1) by up-regulating a pro-apoptotic molecule, FasL, and 2) by down-regulating a survival molecule, gamma c.</abstract><cop>United States</cop><pmid>10477579</pmid><doi>10.4049/jimmunol.163.6.3131</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | AIDS/HIV Animals Antibodies, Blocking - pharmacology Apoptosis - immunology CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cells, Cultured Down-Regulation - immunology Fas Ligand Protein fas Receptor - metabolism Interleukin-2 - physiology Ligands Lymphocyte Activation - immunology Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors Proto-Oncogene Proteins c-bcl-2 - biosynthesis Receptors, Cytokine - antagonists & inhibitors Receptors, Cytokine - biosynthesis Receptors, Cytokine - immunology Receptors, Cytokine - physiology Tumor Necrosis Factor-alpha - antagonists & inhibitors Up-Regulation - immunology |
| title | The role of the common cytokine receptor gamma-chain in regulating IL-2-dependent, activation-induced CD8+ T cell death |
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