Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections
Top Cited Papers
Open Access
- 1 October 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 112 (7), 2826-2835
- https://doi.org/10.1182/blood-2008-05-159301
Abstract
Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, GI tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2) Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the GI tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and GI tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.Keywords
This publication has 53 references indexed in Scilit:
- Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis CGastroenterology, 2008
- Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaquesMucosal Immunology, 2008
- Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndromeNature, 2008
- High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavageMucosal Immunology, 2007
- Immune reconstitution in human immunodeficiency virus type 1-infected children with different virological responses to anti-retroviral therapyClinical and Experimental Immunology, 2007
- Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responsesNature Immunology, 2007
- Phenotypic and functional features of human Th17 cellsThe Journal of Experimental Medicine, 2007
- Microbial translocation is a cause of systemic immune activation in chronic HIV infectionNature Medicine, 2006
- Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptidesThe Journal of Experimental Medicine, 2006
- Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4+T Cells In VivoJournal of Virology, 2006