{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:49:45Z","timestamp":1789372185362,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3226,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Interleukin-7 (IL-7) is required for the establishment and maintenance of memory CD4+ and CD8+ T lymphocytes, and cells lacking IL-7R\u03b1 (CD127) demonstrate impaired IL-2 secretion and have a short life-span. Chronic HCV is characterized by T cells that are functionally impaired and exhibit an immature phenotype. To investigate the potential role of IL-7\/IL-7R\u03b1 in the outcome of HCV infection, we used multiparameter flow cytometry to characterize patients with acute infection (n = 24), long-term chronic infection (12) and normal subjects (13). HCV infection per se resulted in downregulation of CD127 on total CD4+ and CD8+ T lymphocytes as compared to normal controls. Total expression was lowest in those patients who subsequently developed persistence and intermediate in those patients with acute-resolving infection. This reduction affected both na\u00efve and effector\/memory T cells. CD127 correlated phenotypically with upregulation of chemokine receptors CCR7 and CXCR4, expression of the anti-apoptotic molecule B cell leukemia\/lymphoma 2 (Bcl-2), and enhanced IL-2 production. In six HLA A2-positive patients, we longitudinally tracked tetramer responses to HCV and CMV epitopes; at baseline, reflecting the expression of CD127 on whole T cell populations, viral-specific CTLs in patients who became chronic demonstrated lower CD127.<\/jats:bold>\n                                 <jats:bold>\n                                    In conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>, CD127 is a useful marker of functional CD4+ and CD8+ T cells and its expression correlates with virologic outcome of acute HCV. These data provide a mechanistic basis for the observation that CTLs generated in early infection rapidly decline as chronicity is established; CD127 expression should be considered in the design of novel immunotherapeutic approaches.<\/jats:bold>\n                                 <jats:bold>\n                                    Supplementary material for this article can be found on the HEPATOLOGY website\n                                 <\/jats:bold> (http:\/\/interscience.wiley.com\/jpages\/0270-9139\/suppmat\/index.html).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21365","type":"journal-article","created":{"date-parts":[[2006,10,20]],"date-time":"2006-10-20T19:22:19Z","timestamp":1161372139000},"page":"1098-1109","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":94,"title":["Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence"],"prefix":"10.1097","volume":"44","author":[{"given":"Lucy","family":"Golden-Mason","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Castelblanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Klarquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Benlloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo R.","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-6-20241201","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nri778","article-title":"Effector and memory Tcell differentiation: implications for vaccine development.","volume":"2","author":"Kaech","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"R2-6-20241201","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/439669a","article-title":"Exhausted T cells perk up.","volume":"439","author":"Williams","year":"2006","journal-title":"Nature"},{"key":"R3-6-20241201","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0952-7915(02)00333-3","article-title":"Influence of effector molecules on the CD8 T cell response to infection.","volume":"14","author":"Harty","year":"2002","journal-title":"Curr Opin Immunol"},{"key":"R4-6-20241201","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/eji.200425828","article-title":"Inverse correlation between IL7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation.","volume":"35","author":"Lang","year":"2005","journal-title":"Eur J Immunol"},{"key":"R5-6-20241201","doi-asserted-by":"crossref","first-page":"F49","DOI":"10.1084\/jem.20020767","article-title":"Multiple choices: regulation of memory CD8 T cell generation and homeostasis by interleukin (IL)7 and IL15.","volume":"195","author":"Prlic","year":"2002","journal-title":"J Exp Med"},{"key":"R6-6-20241201","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/80868","article-title":"Interleukin7 mediates the homeostasis of naive and memory CD8 T cells in vivo.","volume":"1","author":"Schluns","year":"2000","journal-title":"Nat Immunol"},{"key":"R7-6-20241201","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.4049\/jimmunol.174.10.5926","article-title":"Cutting edge: emergence of CD127 high 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":"R8-6-20241201","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1182\/blood-2005-02-0449","article-title":"IL7 receptor alpha chain expression distinguishes functional subsets of virusspecific human CD8 T cells.","volume":"106","author":"van Leeuwen","year":"2005","journal-title":"Blood"},{"key":"R9-6-20241201","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.4049\/jimmunol.174.5.2900","article-title":"Loss of CD127 expression defines an expansion of effector CD8 T cells in HIVinfected individuals.","volume":"174","author":"Paiardini","year":"2005","journal-title":"J Immunol"},{"key":"R10-6-20241201","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1097\/00042560-200112150-00008","article-title":"Interleukin7 receptor expression on CD8() T cells is reduced in HIV infection and partially restored with effective antiretroviral therapy.","volume":"28","author":"MacPherson","year":"2001","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R11-6-20241201","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/505714","article-title":"Differential antigenic hierarchy associated with spontaneous recovery from HCV: implications for vaccine design.","volume":"194","author":"SmykPearson","year":"2006","journal-title":"J Infect Dis"},{"key":"R12-6-20241201","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1084\/jem.20030239","article-title":"Memory CD8 T cells are required for protection from persistent hepatitis C virus infection.","volume":"197","author":"Shoukry","year":"2003","journal-title":"J Exp Med"},{"key":"R13-6-20241201","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.194.10.1395","article-title":"Determinants of viral clearance and persistence during acute hepatitis C virus infection.","volume":"194","author":"Thimme","year":"2004","journal-title":"J Exp Med"},{"key":"R14-6-20241201","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1084\/jem.191.9.1499","article-title":"Analysis of successful immune responses in persons infected with hepatitis C virus.","volume":"191","author":"Lechner","year":"2000","journal-title":"J Exp Med"},{"key":"R15-6-20241201","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1086\/315450","article-title":"Association of hepatitis C virusspecific CD8 T cells with viral clearance in acute hepatitis C.","volume":"181","author":"Gruner","year":"2000","journal-title":"J Infect Dis"},{"key":"R16-6-20241201","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1084\/jem.20042284","article-title":"Immune evasion versus recovery after acute hepatitis C virus infection from a shared source.","volume":"201","author":"Tester","year":"2005","journal-title":"J Exp Med"},{"key":"R17-6-20241201","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/hep.20749","article-title":"Comprehensive analyses of CD8 T cell responses during longitudinal study of acute human hepatitis C.","volume":"42","author":"Cox","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R18-6-20241201","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.4049\/jimmunol.169.6.3447","article-title":"Impaired effector function of hepatitis C virusspecific CD8 T cells in chronic hepatitis C virus infection.","volume":"169","author":"Wedemeyer","year":"2002","journal-title":"J Immunol"},{"key":"R19-6-20241201","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.1128\/JVI.75.12.5550-5558.2001","article-title":"Sustained dysfunction of antiviral CD8 T lymphocytes after infection with hepatitis C virus.","volume":"75","author":"Gruener","year":"2001","journal-title":"J Virol"},{"key":"R20-6-20241201","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nm0402-379","article-title":"Memory CD8 T cells vary in differentiation phenotype in different persistent virus infections.","volume":"8","author":"Appay","year":"2002","journal-title":"Nature Med"},{"key":"R21-6-20241201","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.4049\/jimmunol.172.3.1744","article-title":"Pervasive influence of hepatitis C virus on the phenotype of antiviral CD8 T cells.","volume":"172","author":"Lucas","year":"2004","journal-title":"J Immunol"},{"key":"R22-6-20241201","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.immuni.2004.07.016","article-title":"Suppression of IL7Ralpha transcription by IL7 and other prosurvival cytokines: a novel mechanism for maximizing IL7dependent T cell survival.","volume":"21","author":"Park","year":"2004","journal-title":"Immunity"},{"key":"R23-6-20241201","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/eji.200425828","article-title":"Inverse correlation between IL7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation.","volume":"35","author":"Lang","year":"2005","journal-title":"Eur J Immunol"},{"key":"R24-6-20241201","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1365-2249.2006.03022.x","article-title":"CD127 expression and regulation are altered in the memory CD8 T cells of HIVinfected patients-reversal by highly active antiretroviral therapy (HAART).","volume":"143","author":"Colle","year":"2006","journal-title":"Clin Exp Immunol"},{"key":"R25-6-20241201","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1086\/499309","article-title":"Increased plasma interleukin7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV1 infection.","volume":"193","author":"Sasson","year":"2006","journal-title":"J Infect Dis"},{"key":"R26-6-20241201","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1189\/jlb.0704424","article-title":"HIV regulation of the IL7R: a viral mechanism for enhancing HIV1 replication in human macrophages in vitro.","volume":"79","author":"Zhang","year":"2006","journal-title":"J Leukoc Biol"},{"key":"R27-6-20241201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-2005-864778","article-title":"Acute hepatitis C: a multifaceted disease.","volume":"25","author":"Heller","year":"2005","journal-title":"Semin Liver Dis"},{"key":"R28-6-20241201","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/hep.20669","article-title":"Preferential loss of IL2secreting CD4 T helper cells in chronic HCV infection.","volume":"41","author":"Semmo","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R29-6-20241201","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/ni1241","article-title":"T cells and viral persistence: lessons from diverse infections.","volume":"6","author":"Klenerman","year":"2005","journal-title":"Nat Immunol"},{"key":"R30-6-20241201","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1128\/JVI.80.7.3532-3540.2006","article-title":"Expression of the interleukin7 receptor alpha chain (CD127) on virusspecific CD8 T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection.","volume":"80","author":"Boettler","year":"2006","journal-title":"J Virol"},{"key":"R31-6-20241201","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.1128\/JVI.78.11.5867-5874.2004","article-title":"Hepatitis C virus persistence after spontaneous or treatmentinduced resolution of hepatitis C.","volume":"78","author":"Pham","year":"2004","journal-title":"J Virol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.21365","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200611000-00006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T13:04:22Z","timestamp":1733058262000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200611000-00006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2006]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.21365","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2006,11]]}}}