Fully Differentiated HIV-1 Specific CD8+ T Effector Cells are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection

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Fully Differentiated HIV-1 Specific CD8+ T Effector Cells are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection

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dc.contributor.author Draenert, Rika
dc.contributor.author Rathod, Almas
dc.contributor.author Verrill, Cori L.
dc.contributor.author Stone, David R.
dc.contributor.author Johnston, Mary N.
dc.contributor.author Flynn, Theresa
dc.contributor.author Addo, Marylyn Martina
dc.contributor.author Davis, Benjamin Thomas
dc.contributor.author Gandhi, Rajesh Tim
dc.contributor.author Robbins, Gregory Kimball
dc.contributor.author Basgov, Nesli
dc.contributor.author Cohen, Daniel E.
dc.contributor.author Wurcel, Alysse Gail
dc.contributor.author Rosenberg, Eric Scott
dc.contributor.author Altfeld, Marcus
dc.contributor.author Walker, Bruce David
dc.date.accessioned 2011-12-24T04:53:04Z
dc.date.issued 2007
dc.identifier.citation Addo, Marylyn M., Rika Draenert, Almas Rathod, Cori L. Verrill, Benjamin T. Davis, Rajesh T. Gandhi, Gregory K. Robbins, et al. 2007. Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection. PLoS ONE 2(3): e321. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978680
dc.description.abstract Background: CD8+ T cells impact control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. In HIV-1 infection, persistent HIV-1 specific IFN-γ+ CD8+ T cell responses are detected in the setting of disease progression, consistent with functional impairment in vivo. Recent data suggest that impaired maturation, as defined by the lineage markers CD45RA and CCR7, may contribute to a lack of immune control by these responses. Methodology/Principal Findings: We investigated the maturation phenotype of epitope-specific CD8+ T cell responses directed against HIV-1 in 42 chronically infected, untreated individuals, 22 of whom were “Controllers” (median 1140 RNA copies/ml plasma, range less than 50 to 2520), and 20 “progressors” of whom had advanced disease and high viral loads (median 135,500 RNA copies/ml plasma, range 12100 to greater than 750000). Evaluation of a mean of 5 epitopes per person revealed that terminally differentiated CD8+ T cells directed against HIV-1 are more often seen in HIV-1 Controllers (16/22; 73%) compared to HIV-1 progressors (7/20; 35%)(p = 0.015), but the maturation state of epitope-specific responses within a given individual was quite variable. Maturation phenotype was independent of the HLA restriction or the specificity of a given CD8+ T cell response and individual epitopes associated with slow disease progression were not more likely to be terminally differentiated. Conclusions/Significance: These data indicate that although full maturation of epitope-specific CD8+ T cell responses is associated with viral control, the maturation status of HIV-1 specific CD8+ T cell responses within a given individual are quite heterogeneous, suggesting epitope-specific influences on CD8+ T cell function. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0000321 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824710/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject immune response en_US
dc.subject HIV infection and AIDS en_US
dc.title Fully Differentiated HIV-1 Specific CD8+ T Effector Cells are More Frequently Detectable in Controlled than in Progressive HIV-1 Infection en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Gandhi, Rajesh Tim
dc.date.available 2011-12-24T04:53:04Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other SPH^Immunology and Infectious Diseases en_US

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