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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Enhanced anti-HIV functional activity associated with gag-specific CD8 T-cell responses
Journal of Virology, Volume 84, No. 11, Year 2010
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Description
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. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2876607/bin/supp_84_11_5540__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2876607/bin/supp_84_11_5540__1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2876607/bin/supp_84_11_5540__Supplemental_Figure1_02031_09.zip
https://efashare.b-cdn.net/share/pmc/articles/PMC2876607/bin/supp_84_11_5540__Legend.doc
Authors & Co-Authors
Jülg, Boris Dominik
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
Williams, Katie L.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
Reddy, Sharon
South Africa, Durban
University of Kwazulu-natal
Bishop, Karen S.
South Africa, Durban
University of Kwazulu-natal
Qi, Ying
United States, Frederick
Saic-frederick
Carrington, Mary N.
United States, Cambridge
Massachusetts Institute of Technology
United States, Frederick
Saic-frederick
Goulder, Philip Jeremy Renshaw
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
United Kingdom, Oxford
Nuffield Department of Medicine
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 114
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1128/JVI.02031-09
ISSN:
0022538X
Research Areas
Infectious Diseases
Study Design
Case-Control Study