Enhanced Anti-HIV Functional Activity Associated with Gag-Specific CD8 T-Cell Responses

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dc.contributor.author Julg, B en
dc.contributor.author Williams, KL en
dc.contributor.author Reddy, S en
dc.contributor.author Bishop, Karen en
dc.contributor.author Qi, Y en
dc.contributor.author Carrington, M en
dc.contributor.author Goulder, PJ en
dc.contributor.author Ndung'u, T en
dc.contributor.author Walker, BD en
dc.date.accessioned 2012-03-01T02:01:58Z en
dc.date.issued 2010-06 en
dc.identifier.citation Journal of Virology 84(11):5540-5549 2010 en
dc.identifier.issn 0022-538X en
dc.identifier.uri http://hdl.handle.net/2292/12405 en
dc.description.abstract Effective HIV-specific T-cell immunity requires the ability to inhibit virus replication in the infected host, but the functional characteristics of cells able to mediate this effect are not well defined. Since Gag-specific CD8 T cells have repeatedly been associated with lower viremia, we examined the influence of Gag specificity on the ability of unstimulated CD8 T cells from chronically infected persons to inhibit virus replication in autologous CD4 T cells. Persons with broad (>6; n 13) or narrow (<1; n 13) Gag-specific responses, as assessed by gamma interferon enzyme-linked immunospot assay, were selected from 288 highly active antiretroviral therapy (HAART)-naive HIV-1 clade C-infected South Africans, matching groups for total magnitude of HIV-specific CD8 T-cell responses and CD4 T-cell counts. CD8 T cells from high Gag responders suppressed in vitro replication of a heterologous HIV strain in autologous CD4 cells more potently than did those from low Gag responders (P < 0.003) and were associated with lower viral loads in vivo (P < 0.002). As previously shown in subjects with low viremia, CD8 T cells from high Gag responders exhibited a more polyfunctional cytokine profile and a stronger ability to proliferate in response to HIV stimulation than did low Gag responders, which mainly exhibited monofunctional CD8 T-cell responses. Furthermore, increased polyfunctionality was significantly correlated with greater inhibition of viral replication in vitro. These data indicate that enhanced suppression of HIV replication is associated with broader targeting of Gag. We conclude that it is not the overall magnitude but rather the breadth, magnitude, and functional capacity of CD8 T-cell responses to certain conserved proteins, like Gag, which predict effective antiviral HIV-specific CD8 T-cell function. en
dc.publisher American Society for Microbiology en
dc.relation.ispartofseries Journal of Virology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0022-538X/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Enhanced Anti-HIV Functional Activity Associated with Gag-Specific CD8 T-Cell Responses en
dc.type Journal Article en
dc.identifier.doi 10.1128/JVI.02031-09. en
pubs.issue 11 en
pubs.begin-page 5540 en
pubs.volume 84 en
dc.rights.holder Copyright: American Society for Microbiology en
dc.identifier.pmid 20335261 en
pubs.end-page 5549 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 196173 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.record-created-at-source-date 2010-12-13 en
pubs.dimensions-id 20335261 en

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