A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers.
HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3031543?pdf=render |
| _version_ | 1819039399034224640 |
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| author | Peter W Hunt Alan L Landay Elizabeth Sinclair Jeffrey A Martinson Hiroyu Hatano Brinda Emu Philip J Norris Michael P Busch Jeffrey N Martin Cicely Brooks Joseph M McCune Steven G Deeks |
| author_facet | Peter W Hunt Alan L Landay Elizabeth Sinclair Jeffrey A Martinson Hiroyu Hatano Brinda Emu Philip J Norris Michael P Busch Jeffrey N Martin Cicely Brooks Joseph M McCune Steven G Deeks |
| author_sort | Peter W Hunt |
| collection | DOAJ |
| description | HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127(dim)), HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed), untreated HIV-infected "non-controllers" with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014). Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P ≤ 0.001). These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion. |
| first_indexed | 2024-12-21T08:52:35Z |
| format | Article |
| id | doaj.art-f0cdf4da9286427d94719244db44c4da |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:52:35Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f0cdf4da9286427d94719244db44c4da2022-12-21T19:09:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1592410.1371/journal.pone.0015924A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers.Peter W HuntAlan L LandayElizabeth SinclairJeffrey A MartinsonHiroyu HatanoBrinda EmuPhilip J NorrisMichael P BuschJeffrey N MartinCicely BrooksJoseph M McCuneSteven G DeeksHIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127(dim)), HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed), untreated HIV-infected "non-controllers" with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014). Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P ≤ 0.001). These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion.http://europepmc.org/articles/PMC3031543?pdf=render |
| spellingShingle | Peter W Hunt Alan L Landay Elizabeth Sinclair Jeffrey A Martinson Hiroyu Hatano Brinda Emu Philip J Norris Michael P Busch Jeffrey N Martin Cicely Brooks Joseph M McCune Steven G Deeks A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. PLoS ONE |
| title | A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. |
| title_full | A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. |
| title_fullStr | A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. |
| title_full_unstemmed | A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. |
| title_short | A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. |
| title_sort | low t regulatory cell response may contribute to both viral control and generalized immune activation in hiv controllers |
| url | http://europepmc.org/articles/PMC3031543?pdf=render |
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