Short Communication: HIV + Viremic Slow Progressors Maintain Low Regulatory T Cell Numbers in Rectal Mucosa but Exhibit High T Cell Activation
Year: 2012
Type: article
Study design: Observational Study
Abstract: Viremic slow progressors (VSP) are a rare subset of HIV-infected persons who exhibit slow immunologic progression despite high viremia. The mechanisms associated with this slow progression remain to be defined. Clinical characteristics of VSP are similar to those of natural hosts for simian immunodeficiency virus (SIV), such as sooty mangabeys (SM) and African green monkeys (AGM), who maintain near-normal CD4 counts despite high-level viremia but maintain low immune activation. Immune activation is a powerful predictor of disease progression, and we hypothesized that low immune activation might also explain the VSP phenotype. Using multiparameter flow cytometry, we assessed levels of T cell activation and regulatory T cells (Treg) in blood and rectal mucosa of VSP, typical progressors, virologic controllers, and seronegative controls. We also assessed Treg function and CD4 T cell proliferative capacity in VSP. Contrary to expectations, we found that VSP subjects have high levels of T cell activation in the gastrointestinal mucosa. The ratio of Treg to CD3+ T cells in the mucosa of VSP was relatively low, potentially contributing to increased immune activation. Nonetheless, CD4+CD25- T cells isolated from these individuals displayed a comparatively weak proliferative response to anti-CD3 stimulation. These data reveal that the VSP phenotype is associated with elevated markers of mucosal immune activation and low numbers of mucosal Treg, suggesting that factors other than immune activation account for this phenotype.
Authors: Julia M. Shaw, Peter W. Hunt, J. William Critchfield, Delandy H. McConnell, Juan Carlos Garcia, Richard B. Pollard, Ma Somsouk, Steven G. Deeks, Barbara L. Shacklett
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: James B. Pendleton Charitable Trust, National Institutes of Health, University of California, Davis, University of California, San Francisco, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1531094742, Clinical and Translational Science Institute, Impact of HIV-associated inflammation on disease, G2184793071, G2839755957, G2881458443, G3322721267, G349814709, HIV, Gut Mucosal Turnover and Inflammation, and the Risk of Colorectal Neoplasia, G3917235369, G4522520631, G5276117644, EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION, G8021174655, G9000058261, G9000074537, G9000078127, G9000081321, UCSF Liver Center, G908307478, G97119092
OpenAlex ID: W2077786609