eprintid: 13665 rev_number: 35 userid: 677 importid: 527 dir: disk0/00/01/36/65 datestamp: 2012-08-25 16:42:53 lastmod: 2021-06-12 21:55:14 status_changed: 2012-08-25 16:42:53 type: article metadata_visibility: show contact_email: William-hildebrand@ouhsc.edu item_issues_count: 0 eprint_status: archive creators_name: Piazza, P creators_name: McMurtrey, CP creators_name: Lelic, A creators_name: Cook, RL creators_name: Hess, R creators_name: Yablonsky, E creators_name: Borowski, L creators_name: Loeb, MB creators_name: Bramson, JL creators_name: Hildebrand, WH creators_name: Rinaldo, CR creators_email: paolo@pitt.edu creators_email: creators_email: creators_email: creators_email: creators_email: ejy3@pitt.edu creators_email: creators_email: creators_email: creators_email: creators_email: RINALDO@pitt.edu creators_id: PAOLO creators_id: creators_id: creators_id: creators_id: creators_id: EJY3 creators_id: creators_id: creators_id: creators_id: creators_id: RINALDO contributors_type: http://www.loc.gov/loc.terms/relators/EDT contributors_name: Sandberg, Johan K. title: Surface phenotype and functionality of WNV Specific T cells differ with age and disease severity ispublished: pub divisions: sch_gsph_infectiousdiseasesmicrobiology full_text_status: public 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. date: 2010-12-01 date_type: published publication: PLoS ONE volume: 5 number: 12 refereed: TRUE id_number: 10.1371/journal.pone.0015343 other_id: NLM PMC3001480 pmcid: PMC3001480 pmid: 21179445 mesh_headings: Age Factors mesh_headings: Antigens, CD27--biosynthesis mesh_headings: Antigens, CD45--metabolism mesh_headings: Antigens, CD57--biosynthesis mesh_headings: CD8-Positive T-Lymphocytes--metabolism mesh_headings: Epitopes--chemistry mesh_headings: HLA-A Antigens--genetics mesh_headings: Humans mesh_headings: Immunologic Memory mesh_headings: Ligands mesh_headings: Phenotype mesh_headings: Receptors, CCR7--metabolism mesh_headings: T-Lymphocytes--virology mesh_headings: West Nile Fever--pathology mesh_headings: West Nile Fever--virology mesh_headings: West Nile virus--genetics chemical_names: Antigens, CD27 chemical_names: Antigens, CD57 chemical_names: CCR7 protein, human chemical_names: Epitopes chemical_names: HLA-A Antigens chemical_names: Ligands chemical_names: Receptors, CCR7 chemical_names: Antigens, CD45 citation: 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). document_url: http://d-scholarship-dev.library.pitt.edu/13665/1/Surface_Phenotype.pdf document_url: http://d-scholarship-dev.library.pitt.edu/13665/8/licence.txt