R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes

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R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes

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Title: R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes
Author: Righi, Elda; Leblanc, Pierre R.; Kodish, Brett; Mylvaganam, Hari N.; Stevceva, Liljana; Hu, Shiu-Lok; Chenine, Agnes-L.; Hovav, Avi-Hai; Unutmaz, Derya; Santosuosso, Michael Robert; Siddappa, Nagadenahalli B.; Ghebremichael, Musie Syum; Ruprecht, Ruth Margrit; Poznansky, Mark; Hill, David E.

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Citation: Santosuosso, Michael, Elda Righi, E. David Hill, Pierre R. Leblanc, Brett Kodish, Hari N. Mylvaganam, Nagadenahalli B. Siddappa et al. 2011. R5-SHIV induces multiple defects in T Cell function during early infection of Rhesus macaques including accumulation of T Reg Cells in lymph nodes. PLoS ONE 6(4): e18465
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Abstract: Background: HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues. Methods: Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation. Results/Conclusions: We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.
Published Version: doi://10.1371/journal.pone.0018465
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071731/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10483960
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