{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:58:26Z","timestamp":1791147506339,"version":"4.1.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To evaluate the impact of sustained viral loads on anti-viral T cell responses we compared responses that cleared acute lymphocytic choriomeningitis virus infection with those that were elicited but could not resolve chronic infection. During acute infection, as replicating virus was cleared, CD8 T cell responses were down-regulated, and a pool of resting memory cells developed. In chronically infected hosts, the failure to control the infection was associated with pronounced and prolonged activation of virus-specific CD8 T cells. Nevertheless, there was a progressive diminution of their effector activities as their capacity to produce first IL-2, then TNF-\u03b1, and finally IFN-\u03b3 was lost. Chronic lymphocytic choriomeningitis virus infection was also associated with differential contraction of certain CD8 T cell responses, resulting in altered immunodominance. However, this altered immunodominance was not due to selective expansion of T cells expressing particular TCR V\u03b2 segments during chronic infection. High viral loads were not only associated with the ablation of CD8 T cell responses, but also with impaired production of IL-2 by virus-specific CD4 T cells. Taken together, our data show that sustained exposure to high viral loads results in the progressive functional inactivation of virus-specific T cell responses, which may further promote virus persistence.<\/jats:p>","DOI":"10.4049\/jimmunol.170.1.477","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T04:11:17Z","timestamp":1398139877000},"page":"477-486","source":"Crossref","is-referenced-by-count":216,"title":["Ablation of CD8 and CD4 T Cell Responses by High Viral Loads"],"prefix":"10.1093","volume":"170","author":[{"given":"Michael J","family":"Fuller","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan J","family":"Zajac","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2025032709202860000_R1","first-page":"285","volume-title":"Fundamental Virology","year":"2001"},{"key":"2025032709202860000_R2","first-page":"313","volume-title":"Adv. Immunol.","year":"1998"},{"key":"2025032709202860000_R3","first-page":"275","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2025032709202860000_R4","first-page":"561","volume-title":"Annu. Rev. Immunol.","year":"2000"},{"key":"2025032709202860000_R5","first-page":"6874","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2025032709202860000_R6","first-page":"289","volume-title":"Effects of Microbes on the Immune System","year":"2000"},{"key":"2025032709202860000_R7","first-page":"9848","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2025032709202860000_R8","first-page":"5550","volume-title":"J. Virol.","year":"2001"},{"key":"2025032709202860000_R9","first-page":"63","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032709202860000_R10","first-page":"F19","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032709202860000_R11","first-page":"248","volume-title":"Science","year":"1998"},{"key":"2025032709202860000_R12","first-page":"167","volume-title":"Immunity","year":"1998"},{"key":"2025032709202860000_R13","first-page":"177","volume-title":"Immunity","year":"1998"},{"key":"2025032709202860000_R14","first-page":"683","volume-title":"Immunity","year":"1998"},{"key":"2025032709202860000_R15","first-page":"1395","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R16","first-page":"15565","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2025032709202860000_R17","first-page":"1993","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R18","first-page":"6081","volume-title":"J. Immunol.","year":"2000"},{"key":"2025032709202860000_R19","first-page":"913","volume-title":"Nat. Med.","year":"2001"},{"key":"2025032709202860000_R20","first-page":"71","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R21","first-page":"31","volume-title":"Nature","year":"1994"},{"key":"2025032709202860000_R22","first-page":"1253","volume-title":"Eur. J. Immunol.","year":"1989"},{"key":"2025032709202860000_R23","first-page":"10854","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1994"},{"key":"2025032709202860000_R24","first-page":"3256","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2025032709202860000_R25","first-page":"977","volume-title":"Cell","year":"1994"},{"key":"2025032709202860000_R26","first-page":"25","volume-title":"Immunity","year":"1996"},{"key":"2025032709202860000_R27","first-page":"825","volume-title":"Science","year":"1999"},{"key":"2025032709202860000_R28","first-page":"1499","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032709202860000_R29","first-page":"2205","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R30","first-page":"3309","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032709202860000_R31","first-page":"379","volume-title":"Nat. Med.","year":"2002"},{"key":"2025032709202860000_R32","first-page":"106","volume-title":"Nature","year":"2001"},{"key":"2025032709202860000_R33","first-page":"493","volume-title":"Nat. Med.","year":"2002"},{"key":"2025032709202860000_R34","first-page":"2755","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2025032709202860000_R35","first-page":"403","volume-title":"Nature","year":"1994"},{"key":"2025032709202860000_R36","first-page":"2505","volume-title":"Blood","year":"2002"},{"key":"2025032709202860000_R37","first-page":"10249","volume-title":"J. Virol.","year":"2000"},{"key":"2025032709202860000_R38","first-page":"758","volume-title":"Nature","year":"1993"},{"key":"2025032709202860000_R39","first-page":"595","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032709202860000_R40","first-page":"421","volume-title":"Semin. Immunol.","year":"1993"},{"key":"2025032709202860000_R41","first-page":"4700","volume-title":"J. Virol.","year":"1994"},{"key":"2025032709202860000_R42","first-page":"8056","volume-title":"J. Virol.","year":"1994"},{"key":"2025032709202860000_R43","first-page":"575","volume-title":"Persistent Viral Infections","year":"1999"},{"key":"2025032709202860000_R44","first-page":"521","volume-title":"J. Exp. Med.","year":"1984"},{"key":"2025032709202860000_R45","first-page":"94","volume-title":"Science","year":"1996"},{"key":"2025032709202860000_R46","first-page":"5526","volume-title":"J. Immunol.","year":"1999"},{"key":"2025032709202860000_R47","first-page":"183","volume-title":"J. Immunol. Methods","year":"1987"},{"key":"2025032709202860000_R48","first-page":"83","volume-title":"Immunopharmacology","year":"1996"},{"key":"2025032709202860000_R49","first-page":"11571","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1994"},{"key":"2025032709202860000_R50","first-page":"3426","volume-title":"J. Immunol.","year":"1994"},{"key":"2025032709202860000_R51","first-page":"1241","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032709202860000_R52","first-page":"76","volume-title":"Nature","year":"1999"},{"key":"2025032709202860000_R53","first-page":"208","volume-title":"J. Immunol.","year":"2000"},{"key":"2025032709202860000_R54","first-page":"4429","volume-title":"J. Virol.","year":"2000"},{"key":"2025032709202860000_R55","first-page":"1354","volume-title":"Science","year":"2000"},{"key":"2025032709202860000_R56","first-page":"619","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2025032709202860000_R57","first-page":"549","volume-title":"Curr. Opin. Immunol.","year":"2001"},{"key":"2025032709202860000_R58","first-page":"1647","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R59","first-page":"51","volume-title":"Annu. Rev. Immunol.","year":"1999"},{"key":"2025032709202860000_R60","first-page":"83","volume-title":"Immunity","year":"2000"},{"key":"2025032709202860000_R61","first-page":"2139","volume-title":"J. Immunol.","year":"1998"},{"key":"2025032709202860000_R62","first-page":"1249","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2025032709202860000_R63","first-page":"181","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032709202860000_R64","first-page":"5387","volume-title":"J. Immunol.","year":"2000"},{"key":"2025032709202860000_R65","first-page":"2105","volume-title":"J. Exp. Med.","year":"1989"},{"key":"2025032709202860000_R66","first-page":"3142","volume-title":"J. Immunol.","year":"1988"},{"key":"2025032709202860000_R67","first-page":"54","volume-title":"Cell. Immunol.","year":"1996"},{"key":"2025032709202860000_R68","first-page":"829","volume-title":"J. Virol.","year":"2002"},{"key":"2025032709202860000_R69","first-page":"8407","volume-title":"J. Virol.","year":"2001"},{"key":"2025032709202860000_R70","first-page":"1383","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2025032709202860000_R71","first-page":"449","volume-title":"Immunity","year":"1998"},{"key":"2025032709202860000_R72","first-page":"340","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032709202860000_R73","first-page":"677","volume-title":"Nat. Med.","year":"1999"},{"key":"2025032709202860000_R74","first-page":"1018","volume-title":"J. Virol.","year":"2000"},{"key":"2025032709202860000_R75","first-page":"1447","volume-title":"Science","year":"1997"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/1\/477\/62565310\/477.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/1\/477\/62565310\/477.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T11:53:36Z","timestamp":1743335616000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/1\/477\/8028603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,1]]},"references-count":75,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.1.477","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,1]]},"published":{"date-parts":[[2003,1,1]]}}}