{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:13:20Z","timestamp":1792516400896,"version":"4.5.0"},"reference-count":58,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,1,16]]},"abstract":"<jats:p>The signaling adaptor TNFR-associated factor 1 (TRAF1) is specifically lost from virus-specific CD8 T cells during the chronic phase of infection with HIV in humans or lymphocytic choriomeningitis virus (LCMV) clone 13 in mice. In contrast, TRAF1 is maintained at higher levels in virus-specific T cells of HIV controllers or after acute LCMV infection. TRAF1 expression negatively correlates with programmed death 1 expression and HIV load and knockdown of TRAF1 in CD8 T cells from viral controllers results in decreased HIV suppression ex vivo. Consistent with the desensitization of the TRAF1-binding co-stimulatory receptor 4-1BB, 4-1BBL\u2013deficient mice have defects in viral control early, but not late, in chronic infection. TGF\u03b2 induces the posttranslational loss of TRAF1, whereas IL-7 restores TRAF1 levels. A combination treatment with IL-7 and agonist anti\u20134-1BB antibody at 3 wk after LCMV clone 13 infection expands T cells and reduces viral load in a TRAF1-dependent manner. Moreover, transfer of TRAF1+ but not TRAF1\u2212 memory T cells at the chronic stage of infection reduces viral load. These findings identify TRAF1 as a potential biomarker of HIV-specific CD8 T cell fitness during the chronic phase of disease and a target for therapy.<\/jats:p>","DOI":"10.1084\/jem.20110675","type":"journal-article","created":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T22:41:19Z","timestamp":1324334479000},"page":"77-91","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection"],"prefix":"10.1084","volume":"209","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann J.","family":"McPherson","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Brad","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim S.","family":"Kawamura","sequence":"additional","affiliation":[{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria H.Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"},{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanuja","family":"Ambagala","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Calzascia","sequence":"additional","affiliation":[{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasra","family":"Aidarus","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha R.","family":"Elford","sequence":"additional","affiliation":[{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng Yun","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Kremmer","sequence":"additional","affiliation":[{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Molecular Immunology, 83177 Munich, Germany 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin M.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Maple Leaf Medical Clinic, Toronto, M5B 1L6, Canada 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Benko","sequence":"additional","affiliation":[{"name":"Maple Leaf Medical Clinic, Toronto, M5B 1L6, Canada 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Tremblay","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie et immunologie, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, H3C 3J7, Canada 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[{"name":"Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital 9 , and 10"},{"name":"Research Institute of the McGill University Health Center, Montreal, H3A 1A1, Canada 9 , and 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Immunodeficiency Service and Division of Hematology, Royal Victoria Hospital 9 , and 10"},{"name":"Research Institute of the McGill University Health Center, Montreal, H3A 1A1, Canada 9 , and 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario A.","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"},{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"},{"name":"Li Ka Shing Knowledge Institute at St. Michael\u2019s Hospital, University of Toronto, Toronto, M5B 1W8, Canada 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"},{"name":"Department of Medical Biophysics, University of Toronto, Toronto, M5G 2M9, Canada 3"},{"name":"The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, M5G 2M9, Canada 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania H.","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 , 2"},{"name":"Clinical Sciences Division, University of Toronto, Toronto, M5S 1A8, Canada 1 , 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,12,19]]},"reference":[{"key":"2023072601023617900_bib1","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling pathways of the TNF superfamily: a double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2023072601023617900_bib2","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence","volume":"160","author":"Ahmed","year":"1984","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/MCB.18.1.558","article-title":"4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB","volume":"18","author":"Arch","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2023072601023617900_bib4","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1084\/jem.20020774","article-title":"Regulation of the subcellular localization of tumor necrosis factor receptor-associated factor (TRAF)2 by TRAF1 reveals mechanisms of TRAF2 signaling","volume":"196","author":"Arron","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib5","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1053\/j.seminoncol.2010.09.008","article-title":"Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies","volume":"37","author":"Ascierto","year":"2010","journal-title":"Semin. Oncol."},{"key":"2023072601023617900_bib6","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature."},{"key":"2023072601023617900_bib7","doi-asserted-by":"publisher","first-page":"20428","DOI":"10.1073\/pnas.0811139106","article-title":"IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection","volume":"105","author":"Brooks","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601023617900_bib8","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1073\/pnas.0306567101","article-title":"Costimulatory ligand 4-1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses","volume":"101","author":"Bukczynski","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601023617900_bib9","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.4049\/jimmunol.175.10.6378","article-title":"Enhancement of HIV-specific CD8 T cell responses by dual costimulation with CD80 and CD137L","volume":"175","author":"Bukczynski","year":"2005","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib10","doi-asserted-by":"publisher","first-page":"4455","DOI":"10.1182\/blood-2007-05-088682","article-title":"Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma","volume":"110","author":"Cerhan","year":"2007","journal-title":"Blood."},{"key":"2023072601023617900_bib11","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nri2526","article-title":"The role of TNF superfamily members in T-cell function and diseases","volume":"9","author":"Croft","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2023072601023617900_bib12","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1038\/sj.cdd.4402192","article-title":"TGF-beta in intestinal lymphoid organs contributes to the death of armed effector CD8 T cells and is associated with the absence of virus containment in rhesus macaques infected with the simian immunodeficiency virus","volume":"14","author":"Cumont","year":"2007","journal-title":"Cell Death Differ."},{"key":"2023072601023617900_bib13","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature."},{"key":"2023072601023617900_bib14","doi-asserted-by":"publisher","first-page":"37909","DOI":"10.1074\/jbc.M109.093724","article-title":"TGF-beta1 protects against mesangial cell apoptosis via induction of autophagy","volume":"285","author":"Ding","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2023072601023617900_bib15","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1084\/jem.20061800","article-title":"Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade","volume":"203","author":"Freeman","year":"2006","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib16","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.4049\/jimmunol.174.10.5926","article-title":"Cutting edge: emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell help","volume":"174","author":"Fuller","year":"2005","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib17","doi-asserted-by":"publisher","first-page":"8627","DOI":"10.1128\/JVI.00855-06","article-title":"Role of Bim in regulating CD8+ T-cell responses during chronic viral infection","volume":"80","author":"Grayson","year":"2006","journal-title":"J. Virol."},{"key":"2023072601023617900_bib18","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.immuni.2008.01.004","article-title":"Fas Bim boom!","volume":"28","author":"Green","year":"2008","journal-title":"Immunity."},{"key":"2023072601023617900_bib19","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1006\/bbrc.1997.8016","article-title":"Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B","volume":"242","author":"Jang","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072601023617900_bib20","doi-asserted-by":"publisher","first-page":"14733","DOI":"10.1073\/pnas.1009731107","article-title":"Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection","volume":"107","author":"Jin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601023617900_bib21","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1084\/jem.20081398","article-title":"Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection","volume":"205","author":"Jones","year":"2008","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib22","doi-asserted-by":"publisher","first-page":"e278","DOI":"10.1371\/journal.pmed.0040278","article-title":"A candidate gene approach identifies the TRAF1\/C5 region as a risk factor for rheumatoid arthritis","volume":"4","author":"Kurreeman","year":"2007","journal-title":"PLoS Med."},{"key":"2023072601023617900_bib23","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1002\/eji.200425828","article-title":"Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation","volume":"35","author":"Lang","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"2023072601023617900_bib24","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-0-387-70630-6_2","article-title":"TRAF1 and its biological functions","volume":"597","author":"Lee","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023072601023617900_bib25","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.4049\/jimmunol.169.9.4882","article-title":"4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1","volume":"169","author":"Lee","year":"2002","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib26","first-page":"997","article-title":"Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment","volume":"119","author":"Levy","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2023072601023617900_bib27","doi-asserted-by":"publisher","first-page":"11876","DOI":"10.1128\/JVI.01153-09","article-title":"Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy","volume":"83","author":"Migueles","year":"2009","journal-title":"J. Virol."},{"key":"2023072601023617900_bib28","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.4049\/jimmunol.178.7.4194","article-title":"Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice","volume":"178","author":"Niu","year":"2007","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib29","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1093\/emboj\/17.2.384","article-title":"Bim: a novel member of the Bcl-2 family that promotes apoptosis","volume":"17","author":"O\u2019Connor","year":"1998","journal-title":"EMBO J."},{"key":"2023072601023617900_bib30","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nm.1953","article-title":"Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies","volume":"15","author":"Pellegrini","year":"2009","journal-title":"Nat. Med."},{"key":"2023072601023617900_bib31","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.cell.2011.01.011","article-title":"IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology","volume":"144","author":"Pellegrini","year":"2011","journal-title":"Cell."},{"key":"2023072601023617900_bib32","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1084\/jem.20061496","article-title":"PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection","volume":"203","author":"Petrovas","year":"2006","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib33","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/342559a0","article-title":"Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen","volume":"342","author":"Pircher","year":"1989","journal-title":"Nature."},{"key":"2023072601023617900_bib34","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa073491","article-title":"TRAF1-C5 as a risk locus for rheumatoid arthritis\u2014a genomewide study","volume":"357","author":"Plenge","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"2023072601023617900_bib35","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.4049\/jimmunol.176.5.2739","article-title":"IL-15-dependent induction of 4-1BB promotes antigen-independent CD8 memory T cell survival","volume":"176","author":"Pulle","year":"2006","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib36","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/0092-8674(94)90532-0","article-title":"A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor","volume":"78","author":"Rothe","year":"1994","journal-title":"Cell."},{"key":"2023072601023617900_bib37","doi-asserted-by":"publisher","first-page":"18703","DOI":"10.1073\/pnas.0602919103","article-title":"A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival","volume":"103","author":"Sabbagh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601023617900_bib38","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.4049\/jimmunol.180.12.8093","article-title":"ERK-dependent Bim modulation downstream of the 4-1BB-TRAF1 signaling axis is a critical mediator of CD8 T cell survival in vivo","volume":"180","author":"Sabbagh","year":"2008","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib39","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1128\/jvi.65.4.1863-1869.1991","article-title":"Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence","volume":"65","author":"Salvato","year":"1991","journal-title":"J. Virol."},{"key":"2023072601023617900_bib40","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1084\/jem.187.11.1849","article-title":"CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand","volume":"187","author":"Saoulli","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib41","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.vaccine.2009.09.127","article-title":"A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity","volume":"28","author":"Schabowsky","year":"2009","journal-title":"Vaccine."},{"key":"2023072601023617900_bib42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1600-065X.2009.00784.x","article-title":"Mechanisms of costimulation","volume":"229","author":"Sharpe","year":"2009","journal-title":"Immunol. Rev."},{"key":"2023072601023617900_bib43","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1084\/jem.186.1.47","article-title":"4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses","volume":"186","author":"Shuford","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib44","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1136\/mp.56.3.156","article-title":"Epstein-Barr virus encoded latent membrane protein 1 (LMP1) and TNF receptor associated factors (TRAF): colocalisation of LMP1 and TRAF1 in primary EBV infection and in EBV associated Hodgkin lymphoma","volume":"56","author":"Siegler","year":"2003","journal-title":"MP, Mol. Pathol."},{"key":"2023072601023617900_bib45","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1084\/jem.185.10.1777","article-title":"A regulatory role for TRAF1 in antigen-induced apoptosis of T cells","volume":"185","author":"Speiser","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib46","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.immuni.2009.06.015","article-title":"Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo","volume":"31","author":"Tinoco","year":"2009","journal-title":"Immunity."},{"key":"2023072601023617900_bib47","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/nm1482","article-title":"Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction","volume":"12","author":"Trautmann","year":"2006","journal-title":"Nat. Med."},{"key":"2023072601023617900_bib48","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/S1074-7613(01)00207-2","article-title":"TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice","volume":"15","author":"Tsitsikov","year":"2001","journal-title":"Immunity."},{"key":"2023072601023617900_bib49","doi-asserted-by":"publisher","first-page":"11398","DOI":"10.1128\/JVI.01177-06","article-title":"PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion","volume":"80","author":"Urbani","year":"2006","journal-title":"J. Virol."},{"key":"2023072601023617900_bib50","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1128\/JVI.00024-07","article-title":"Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination","volume":"81","author":"Velu","year":"2007","journal-title":"J. Virol."},{"key":"2023072601023617900_bib51","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cell.2009.06.036","article-title":"Redefining chronic viral infection","volume":"138","author":"Virgin","year":"2009","journal-title":"Cell."},{"key":"2023072601023617900_bib52","doi-asserted-by":"crossref","first-page":"8252","DOI":"10.4049\/jimmunol.179.12.8252","article-title":"4-1BBL induces TNF receptor-associated factor 1-dependent Bim modulation in human T cells and is a critical component in the costimulation-dependent rescue of functionally impaired HIV-specific CD8 T cells","volume":"179","author":"Wang","year":"2007","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib53","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev.immunol.23.021704.115839","article-title":"TNF\/TNFR family members in costimulation of T cell responses","volume":"23","author":"Watts","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2023072601023617900_bib54","doi-asserted-by":"publisher","first-page":"16004","DOI":"10.1073\/pnas.0407192101","article-title":"Antigen-independent memory CD8 T cells do not develop during chronic viral infection","volume":"101","author":"Wherry","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072601023617900_bib55","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity."},{"key":"2023072601023617900_bib56","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T cells without effector function","volume":"188","author":"Zajac","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072601023617900_bib57","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.4049\/jimmunol.165.9.5084","article-title":"TNFR-associated factor family protein expression in normal tissues and lymphoid malignancies","volume":"165","author":"Zapata","year":"2000","journal-title":"J. Immunol."},{"key":"2023072601023617900_bib58","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.molcel.2010.03.009","article-title":"Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation","volume":"38","author":"Zheng","year":"2010","journal-title":"Mol. Cell."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/1\/77\/1744344\/jem_20110675.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/1\/77\/1744344\/jem_20110675.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T21:03:32Z","timestamp":1690319012000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/209\/1\/77\/40975\/Loss-of-the-signaling-adaptor-TRAF1-causes-CD8-T"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,19]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1,16]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20110675","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13985972.15442062","asserted-by":"object"}]},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2011,12,19]]}}}