Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers
CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting...
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| Veröffentlicht in: | Blood 2007-02, Vol.109 (3), p.1138-1146 |
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| creator | Heller, Kevin N. Upshaw, Jenica Seyoum, Beza Zebroski, Henry Münz, Christian |
| description | CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4+ T cells belonged to the central-memory compartment (TCM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1-polarized effector cells. |
| doi_str_mv | 10.1182/blood-2006-05-023663 |
| format | Article |
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EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4+ T cells belonged to the central-memory compartment (TCM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were TH1 committed. 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Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1-polarized effector cells.</description><subject>Antigens, Viral - immunology</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cells, Cultured</subject><subject>Epstein-Barr Virus Nuclear Antigens - immunology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Immunologic Memory</subject><subject>Infectious diseases</subject><subject>Interferons - metabolism</subject><subject>Medical sciences</subject><subject>T-Cell Antigen Receptor Specificity</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Th1 Cells - immunology</subject><subject>Viral diseases</subject><subject>Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-P0zAQxS0EYsvCN0DIF7iggB07iX1BWrrLH2klLsvZmriT1iixi-1U6o2PjksjdrkgH-bwfjOeeY-Ql5y941zV7_sxhE1VM9ZWrKlYLdpWPCIr3tSqYqxmj8mKnUSpO35BnqX0gzEuRd08JRe81arhHV-RX9cuZedtphNOIR7p-lq-pXeVxXGkae4T5lSkjYOM1E3T7JFGtGHrXXbB0zDQm33K6Dz9CDHSg4tzon62I0Kk4LPboqecFn2HMObdcUFsoR3G9Jw8GWBM-GKpl-T7p5u79Zfq9tvnr-ur28pKzXOFsjwhBFNcqmHQWouhU3zoBAcLIPpBMaERNkJDbzWvW1C1Zn236ZFrqMUl-XCeu5_7co9FnyOMZh_dBPFoAjjzr-LdzmzDwfCuWCVFGfBmGRDDzxlTNpNLJ5vAY5iTaZWWrWBNAeUZtDGkFHH4-wln5hSd-ROdOUVnWGPO0ZW2Vw8XvG9asirA6wWAZGEcInjr0j2nZKeFfnApFjsPxWOTrENvS4gluWw2wf1_k98Ekbqk</recordid><startdate>20070201</startdate><enddate>20070201</enddate><creator>Heller, Kevin N.</creator><creator>Upshaw, Jenica</creator><creator>Seyoum, Beza</creator><creator>Zebroski, Henry</creator><creator>Münz, Christian</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070201</creationdate><title>Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers</title><author>Heller, Kevin N. ; Upshaw, Jenica ; Seyoum, Beza ; Zebroski, Henry ; Münz, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-e4e4e33308148ff9993f781f731acaa3bf8039ead39abc9126a8290b7dbe19a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Antigens, Viral - immunology</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cells, Cultured</topic><topic>Epstein-Barr Virus Nuclear Antigens - immunology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Immunologic Memory</topic><topic>Infectious diseases</topic><topic>Interferons - metabolism</topic><topic>Medical sciences</topic><topic>T-Cell Antigen Receptor Specificity</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Th1 Cells - immunology</topic><topic>Viral diseases</topic><topic>Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heller, Kevin N.</creatorcontrib><creatorcontrib>Upshaw, Jenica</creatorcontrib><creatorcontrib>Seyoum, Beza</creatorcontrib><creatorcontrib>Zebroski, Henry</creatorcontrib><creatorcontrib>Münz, Christian</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heller, Kevin N.</au><au>Upshaw, Jenica</au><au>Seyoum, Beza</au><au>Zebroski, Henry</au><au>Münz, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2007-02-01</date><risdate>2007</risdate><volume>109</volume><issue>3</issue><spage>1138</spage><epage>1146</epage><pages>1138-1146</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>CD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4+ T cells belonged to the central-memory compartment (TCM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were TH1 committed. 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| ispartof | Blood, 2007-02, Vol.109 (3), p.1138-1146 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antigens, Viral - immunology Biological and medical sciences CD4-Positive T-Lymphocytes - immunology Cells, Cultured Epstein-Barr Virus Nuclear Antigens - immunology Human viral diseases Humans Immunobiology Immunologic Memory Infectious diseases Interferons - metabolism Medical sciences T-Cell Antigen Receptor Specificity T-Lymphocyte Subsets - immunology Th1 Cells - immunology Viral diseases Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye |
| title | Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers |
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