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Surface phenotype and functionality of WNV Specific T cells differ with age and disease severity

Piazza, P and McMurtrey, CP and Lelic, A and Cook, RL and Hess, R and Yablonsky, E and Borowski, L and Loeb, MB and Bramson, JL and Hildebrand, WH and Rinaldo, CR (2010) Surface phenotype and functionality of WNV Specific T cells differ with age and disease severity. PLoS ONE, 5 (12).

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Abstract

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, TNF α, 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. © 2010 Piazza et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Piazza, Ppaolo@pitt.eduPAOLO
McMurtrey, CP
Lelic, A
Cook, RL
Hess, R
Yablonsky, Eejy3@pitt.eduEJY3
Borowski, L
Loeb, MB
Bramson, JL
Hildebrand, WH
Rinaldo, CRRINALDO@pitt.eduRINALDO
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSandberg, Johan K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0015343
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Age Factors; Antigens, CD27--biosynthesis; Antigens, CD45--metabolism; Antigens, CD57--biosynthesis; CD8-Positive T-Lymphocytes--metabolism; Epitopes--chemistry; HLA-A Antigens--genetics; Humans; Immunologic Memory; Ligands; Phenotype; Receptors, CCR7--metabolism; T-Lymphocytes--virology; West Nile Fever--pathology; West Nile Fever--virology; West Nile virus--genetics
Other ID: NLM PMC3001480
PubMed Central ID: PMC3001480
PubMed ID: 21179445
Date Deposited: 25 Aug 2012 16:42
Last Modified: 04 Jan 2020 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13665

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