Righi, EldaLeblanc, Pierre R.Kodish, BrettMylvaganam, Hari N.Stevceva, LiljanaHu, Shiu-LokChenine, Agnes-L.Hovav, Avi-HaiUnutmaz, DeryaSantosuosso, Michael RobertSiddappa, Nagadenahalli B.Ghebremichael, MusieRuprecht, Ruth MargritPoznansky, MarkHill, David2013-04-012011Santosuosso, 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): e184651932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10483960Background: 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.en-USbiologyimmunologyimmune cellsT Cellsimmune systemcytokineslymphoid organsimmunityadaptive immunityimmune activationimmune defenseimmunity to infectionsimmune responseimmunomodulationimmunopathologymicrobiologyvirologyimmunodeficiency virusesviral immune evasionmodel organismsanimal modelsmacaquemedicineJournal Article2013-04-0110.1371/journal.pone.0018465