R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes.
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 hypothes...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3071731?pdf=render |
| _version_ | 1818142553598328832 |
|---|---|
| author | Michael Santosuosso Elda Righi E David Hill Pierre R Leblanc Brett Kodish Hari N Mylvaganam Nagadenahalli B Siddappa Liljana Stevceva Shiu-Lok Hu Musie Ghebremichael Agnes-L Chenine Avi-Hai Hovav Ruth M Ruprecht Mark C Poznansky |
| author_facet | Michael Santosuosso Elda Righi E David Hill Pierre R Leblanc Brett Kodish Hari N Mylvaganam Nagadenahalli B Siddappa Liljana Stevceva Shiu-Lok Hu Musie Ghebremichael Agnes-L Chenine Avi-Hai Hovav Ruth M Ruprecht Mark C Poznansky |
| author_sort | Michael Santosuosso |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-11T11:17:36Z |
| format | Article |
| id | doaj.art-076a6baa71d24720a35ccc23a5f3479d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T11:17:36Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-076a6baa71d24720a35ccc23a5f3479d2022-12-22T01:09:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1846510.1371/journal.pone.0018465R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes.Michael SantosuossoElda RighiE David HillPierre R LeblancBrett KodishHari N MylvaganamNagadenahalli B SiddappaLiljana StevcevaShiu-Lok HuMusie GhebremichaelAgnes-L ChenineAvi-Hai HovavRuth M RuprechtMark C PoznanskyHIV-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.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.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.http://europepmc.org/articles/PMC3071731?pdf=render |
| spellingShingle | Michael Santosuosso Elda Righi E David Hill Pierre R Leblanc Brett Kodish Hari N Mylvaganam Nagadenahalli B Siddappa Liljana Stevceva Shiu-Lok Hu Musie Ghebremichael Agnes-L Chenine Avi-Hai Hovav Ruth M Ruprecht Mark C Poznansky 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 |
| 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. |
| title_full | R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes. |
| title_fullStr | R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes. |
| title_full_unstemmed | R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes. |
| title_short | R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes. |
| title_sort | r5 shiv induces multiple defects in t cell function during early infection of rhesus macaques including accumulation of t reg cells in lymph nodes |
| url | http://europepmc.org/articles/PMC3071731?pdf=render |
| work_keys_str_mv | AT michaelsantosuosso r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT eldarighi r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT edavidhill r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT pierrerleblanc r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT brettkodish r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT harinmylvaganam r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT nagadenahallibsiddappa r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT liljanastevceva r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT shiulokhu r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT musieghebremichael r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT agneslchenine r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT avihaihovav r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT ruthmruprecht r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes AT markcpoznansky r5shivinducesmultipledefectsintcellfunctionduringearlyinfectionofrhesusmacaquesincludingaccumulationoftregcellsinlymphnodes |