Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.
West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inade...
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doaj-a44c8b49ca0a4d189411cdb7694116652020-11-25T02:47:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-12-01512e1534310.1371/journal.pone.0015343Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.Paolo PiazzaCurtis P McMurtreyAlina LelicRobert L CookRachel HessEric YablonskyLuann BorowskiMark B LoebJonathan L BramsonWilliam H HildebrandCharles R RinaldoWest Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes were assessed in 40 WNV seropositive patients displaying diverse clinical symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific CD8+ T cells were found in peripheral blood several months post infection. The number of WNV-specific T cells in older individuals was the same, if not greater, than in younger members of the cohort. WNV-specific T cells were predominantly monofunctional for CD107a, MIP-1β, TNFα, IL-2, or IFNγ. When CD8+ T cell responses were stratified by disease severity, an increased number of terminally differentiated, memory phenotype (CD45RA+ CD27- CCR7- CD57+) T cells were detected in patients suffering from viral neuroinvasion. In conclusion, T cells of a terminally differentiated/cytolytic profile are associated with neuroinvasion and, regardless of age, monofunctional T cells persist following infection. These data provide the first indication that particular CD8+ T cell phenotypes are associated with disease outcome following WNV infection.http://europepmc.org/articles/PMC3001480?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paolo Piazza Curtis P McMurtrey Alina Lelic Robert L Cook Rachel Hess Eric Yablonsky Luann Borowski Mark B Loeb Jonathan L Bramson William H Hildebrand Charles R Rinaldo |
spellingShingle |
Paolo Piazza Curtis P McMurtrey Alina Lelic Robert L Cook Rachel Hess Eric Yablonsky Luann Borowski Mark B Loeb Jonathan L Bramson William H Hildebrand Charles R Rinaldo Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. PLoS ONE |
author_facet |
Paolo Piazza Curtis P McMurtrey Alina Lelic Robert L Cook Rachel Hess Eric Yablonsky Luann Borowski Mark B Loeb Jonathan L Bramson William H Hildebrand Charles R Rinaldo |
author_sort |
Paolo Piazza |
title |
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. |
title_short |
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. |
title_full |
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. |
title_fullStr |
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. |
title_full_unstemmed |
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity. |
title_sort |
surface phenotype and functionality of wnv specific t cells differ with age and disease severity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-12-01 |
description |
West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes were assessed in 40 WNV seropositive patients displaying diverse clinical symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific CD8+ T cells were found in peripheral blood several months post infection. The number of WNV-specific T cells in older individuals was the same, if not greater, than in younger members of the cohort. WNV-specific T cells were predominantly monofunctional for CD107a, MIP-1β, TNFα, IL-2, or IFNγ. When CD8+ T cell responses were stratified by disease severity, an increased number of terminally differentiated, memory phenotype (CD45RA+ CD27- CCR7- CD57+) T cells were detected in patients suffering from viral neuroinvasion. In conclusion, T cells of a terminally differentiated/cytolytic profile are associated with neuroinvasion and, regardless of age, monofunctional T cells persist following infection. These data provide the first indication that particular CD8+ T cell phenotypes are associated with disease outcome following WNV infection. |
url |
http://europepmc.org/articles/PMC3001480?pdf=render |
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