A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers
Year: 2011
Type: article
Study design: Observational Study
Abstract: 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.
Source: PLoS ONE
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Ragon Institute of MGH, MIT and Harvard, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Francisco, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Center for AIDS Prevention Studies, University of California, San Francisco
Awards: G1024118104, (CHAVI) Center for HIV/AIDS Vaccine Immunology, G149010549, G1531094742, G1572886882, G1647758084, Clinical and Translational Science Institute, G1808123841, UCSF-GIVI CENTER FOR AIDS RESEARCH, G200995756, The Determinants of T Cell Activation in HIV Infection, G2026096560, G2497093736, G3322721267, G3349138028, DYNAMICS OF HIV1 SPECIFIC CTL IN HIV1 INFECTION, Defining the Pathogenesis of Immune Deficiency in Chronic HIV Infection, G5418282550, G5418471891, G6091318935, G6506815201, Basic and Comparative Studies of CCR5 Inhibition to Prevent HIV Transmission, G758528517, (CHAVI) Center for HIV/AIDS Vaccine Immunology, G7717753738, G7998845928, G81379742, G841415025, G9000008089, G9000036821, G9000050168, G9000058261, G9000103698, G9000193691, G9000226269, G97119092
OpenAlex ID: W1967168398