Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease
MHC/self peptide interactions with cognate coreceptor/TCR complexes are central to homeostasis of the T cell repertoire. Recent reports have also underlined the critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In this study, we investigate mechanisms that regulate potent...
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| Veröffentlicht in: | The Journal of immunology (1950) 2002-05, Vol.168 (10), p.4960-4967 |
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| container_issue | 10 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 168 |
| creator | Trimble, Linda A Prince, Kenya A Pestano, Gary A Daley, John Cantor, Harvey |
| description | MHC/self peptide interactions with cognate coreceptor/TCR complexes are central to homeostasis of the T cell repertoire. Recent reports have also underlined the critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In this study, we investigate mechanisms that regulate potentially autoreactive CD8 cells that have escaped intrathymic selection. These cells, upon exit from the thymus, express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas-dependent apoptosis. Defects in fas signaling allow increased IL-15/IL-2-dependent survival of these CD44/B220(+) CD8(+) as well as the double-negative T cells characteristic of lpr disease. |
| doi_str_mv | 10.4049/jimmunol.168.10.4960 |
| format | Article |
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Recent reports have also underlined the critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In this study, we investigate mechanisms that regulate potentially autoreactive CD8 cells that have escaped intrathymic selection. These cells, upon exit from the thymus, express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas-dependent apoptosis. 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Defects in fas signaling allow increased IL-15/IL-2-dependent survival of these CD44/B220(+) CD8(+) as well as the double-negative T cells characteristic of lpr disease.</description><subject>Animals</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle - immunology</subject><subject>Cell Death - genetics</subject><subject>Cell Death - immunology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - immunology</subject><subject>Clonal Deletion - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>fas Receptor - genetics</subject><subject>fas Receptor - physiology</subject><subject>Female</subject><subject>H-2 Antigens - metabolism</subject><subject>Homeostasis - genetics</subject><subject>Homeostasis - immunology</subject><subject>Hyaluronan Receptors - biosynthesis</subject><subject>Leukocyte Common Antigens - biosynthesis</subject><subject>Lymphoproliferative Disorders - genetics</subject><subject>Lymphoproliferative Disorders - immunology</subject><subject>Lymphoproliferative Disorders - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred MRL lpr</subject><subject>Mice, Transgenic</subject><subject>Peptide Fragments - metabolism</subject><subject>Receptors, Interleukin-2 - biosynthesis</subject><subject>Receptors, Interleukin-2 - physiology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - immunology</subject><subject>Thymus Gland - immunology</subject><subject>Thymus Gland - metabolism</subject><subject>Thymus Gland - pathology</subject><subject>Up-Regulation - genetics</subject><subject>Up-Regulation - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1P20AQhleoiKSUf1BVPlW9OMzY6_04Qj4KEoILPa-W3XHZaG0Hr6OIf4_TpIIblxlp9LyvRg9j3xFmHLi-XIem2bZdnKFQs_1RCzhhU6wqyIUA8YVNAYoiRynkhH1NaQ0AAgp-xiaIWnPO5ZRdr2zKF7Sh1lM7ZMsYmtDaIXRt1tXZfdcmiuQG8tl8obI5xZgy2_osbvpsERLZRN_YaW1joovjPmd_VsvH-U1-9_D7dn51l7tSyGGcSpUeCyfJO1cpwEI7bQuOriZ0qnY1eAWCE5Wl56BEVXjyshKopQZZnrOfh95N371sKQ2mCcmNH9mWum0yEoVAzuFTEFWpdYF7kB9A13cp9VSbTR8a278aBLOXbP5LNqPkf8dR8hj7cezfPjXk30NHqyPw6wA8h7_Pu9CTSY2NccTR7Ha7j11v3N6Gig</recordid><startdate>20020515</startdate><enddate>20020515</enddate><creator>Trimble, Linda A</creator><creator>Prince, Kenya A</creator><creator>Pestano, Gary A</creator><creator>Daley, John</creator><creator>Cantor, Harvey</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20020515</creationdate><title>Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease</title><author>Trimble, Linda A ; Prince, Kenya A ; Pestano, Gary A ; Daley, John ; Cantor, Harvey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-c3883d12c7edcc580129c9a241cfe1c8fcf0d8064ee33d408652ded7561979073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - pathology</topic><topic>Cell Cycle - genetics</topic><topic>Cell Cycle - immunology</topic><topic>Cell Death - genetics</topic><topic>Cell Death - immunology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Movement - genetics</topic><topic>Cell Movement - immunology</topic><topic>Clonal Deletion - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>fas Receptor - genetics</topic><topic>fas Receptor - physiology</topic><topic>Female</topic><topic>H-2 Antigens - metabolism</topic><topic>Homeostasis - genetics</topic><topic>Homeostasis - immunology</topic><topic>Hyaluronan Receptors - biosynthesis</topic><topic>Leukocyte Common Antigens - biosynthesis</topic><topic>Lymphoproliferative Disorders - genetics</topic><topic>Lymphoproliferative Disorders - immunology</topic><topic>Lymphoproliferative Disorders - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred MRL lpr</topic><topic>Mice, Transgenic</topic><topic>Peptide Fragments - metabolism</topic><topic>Receptors, Interleukin-2 - biosynthesis</topic><topic>Receptors, Interleukin-2 - physiology</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - immunology</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><topic>Thymus Gland - pathology</topic><topic>Up-Regulation - genetics</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trimble, Linda A</creatorcontrib><creatorcontrib>Prince, Kenya A</creatorcontrib><creatorcontrib>Pestano, Gary A</creatorcontrib><creatorcontrib>Daley, John</creatorcontrib><creatorcontrib>Cantor, Harvey</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</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>Trimble, Linda A</au><au>Prince, Kenya A</au><au>Pestano, Gary A</au><au>Daley, John</au><au>Cantor, Harvey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2002-05-15</date><risdate>2002</risdate><volume>168</volume><issue>10</issue><spage>4960</spage><epage>4967</epage><pages>4960-4967</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>MHC/self peptide interactions with cognate coreceptor/TCR complexes are central to homeostasis of the T cell repertoire. Recent reports have also underlined the critical role of IL-15/IL-2 cytokines in regulating this homeostatic process. In this study, we investigate mechanisms that regulate potentially autoreactive CD8 cells that have escaped intrathymic selection. These cells, upon exit from the thymus, express high levels of CD44, B220, and the IL-15R/IL-2R, and undergo fas-dependent apoptosis. Defects in fas signaling allow increased IL-15/IL-2-dependent survival of these CD44/B220(+) CD8(+) as well as the double-negative T cells characteristic of lpr disease.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11994447</pmid><doi>10.4049/jimmunol.168.10.4960</doi><tpages>8</tpages></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Animals CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - pathology Cell Cycle - genetics Cell Cycle - immunology Cell Death - genetics Cell Death - immunology Cell Differentiation - genetics Cell Differentiation - immunology Cell Movement - genetics Cell Movement - immunology Clonal Deletion - genetics DNA-Binding Proteins - metabolism fas Receptor - genetics fas Receptor - physiology Female H-2 Antigens - metabolism Homeostasis - genetics Homeostasis - immunology Hyaluronan Receptors - biosynthesis Leukocyte Common Antigens - biosynthesis Lymphoproliferative Disorders - genetics Lymphoproliferative Disorders - immunology Lymphoproliferative Disorders - pathology Male Mice Mice, Inbred C57BL Mice, Inbred MRL lpr Mice, Transgenic Peptide Fragments - metabolism Receptors, Interleukin-2 - biosynthesis Receptors, Interleukin-2 - physiology Signal Transduction - genetics Signal Transduction - immunology Thymus Gland - immunology Thymus Gland - metabolism Thymus Gland - pathology Up-Regulation - genetics Up-Regulation - immunology |
| title | Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease |
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