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- Title
Susceptibility of Human Th17 Cells to Human Immunodeficiency Virus and Their Perturbation during Infection.
- Authors
El Hed, Aimee; Khaitan, Alka; Kozhaya, Lina; Manel, Nicolas; Daskalakis, Demetre; Borkowsky, William; Valentine, Fred; Littman, Dan R.; Unutmaz, Derya
- Abstract
Background. Identification of the Th17 T cell subset as important mediators of host defense and pathology prompted us to determine their susceptibility to human immunodeficiency virus (HIV) infection. Methods and results. We found that a sizeable portion of Th17 cells express HIV coreceptor CCR5 and produce very low levels of CCR5 ligands macrophage inflammatory protein (MIP)-1α and MIP-1β. Accordingly, CCR5+ Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV-infected individuals receiving treatment had significantly reduced Th17 cell counts, compared with HIV-uninfected subjects, regardless of viral load or CD4 cell count, whereas treatment-naive subjects had normal levels. However, there was a preferential reduction in CCR5+ T cells that were also CCR6 positive, which is expressed on all Th17 cells, compared with CCR-SCCR5+ cells, in both treated and untreated HIV-infected subjects. This observation suggests preferential targeting of CCR6+CCR5+ Th17 cells by CCR5-tropic viruses in vivo. Th17 cell levels also inversely correlated with activated CD4+ T cells in HIV-infected individuals who are receiving treatment. Conclusions. Our findings suggest a complex perturbation of Th17 subsets during the course of HIV disease potentially through both direct viral infection and virus indirect mechanisms, such as immune activation.
- Subjects
DISEASE susceptibility; HIV; HIV infections; T cells; PATHOLOGY; CHEMOKINES; MEDICAL sciences; IMMUNOGLOBULIN E; CANDIDA
- Publication
Journal of Infectious Diseases, 2010, Vol 201, Issue 6, p843
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/651021