Dataset Information

Airway CD8+CD161++TCRv?7.2+ T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells.

ABSTRACT: HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8+CD161++TCRv?7.2+ T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8+CD161++TCRv?7.2+ T cells in the airway that exhibited a distinct cytokine functional profile compared to their CD103- airway counterparts and those from peripheral blood. These CD103 expressing airway CD8+CD161++TCRv?7.2+ T cells were selectively depleted in untreated HIV-infected adults compared to healthy controls. Their frequency was positively correlated with frequency of airway CD4+ T cells. Furthermore, the frequency of airway CD8+CD161++TCRv?7.2+ T cells was also inversely correlated with HIV plasma viral load, while suppressive antiretroviral therapy (ART) resulted in restoration of airway CD8+CD161++TCRv?7.2+ T cells. Our findings show that CD103 expressing airway CD8+CD161++TCRv?7.2+ T cells are functionally distinct and are preferentially depleted during untreated asymptomatic HIV infection. Depletion of CD103 expressing airway CD8+CD161++TCRv?7.2+ T cells, at a major portal of pathogen entry, could partly contribute to the increased propensity for opportunistic LRTIs observed in untreated HIV-infected adults.

SUBMITTER: Mvaya L

PROVIDER: S-EPMC6713019 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Airway CD8+CD161++TCRvα7.2+ T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells.

Mvaya Leonard L Mwale Andrew A Hummel Annemarie A Phiri Joseph J Kamng'ona Raphael R Mzinza David D Chimbayo Elizabeth E Malamba Rose R Kankwatira Anstead A Mwandumba Henry C HC Jambo Kondwani C KC

Frontiers in immunology 20190821

HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8+CD161++TCRvα7.2+ T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8+</ ...[more]

PMID: 31497028

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Project description:Both HIV and HCV infections feature increased microbial translocation (MT) and gut dysbiosis that affect immune homeostasis and disease outcome. Given their commitment to antimicrobial mucosal immunity, we investigated mucosal-associated invariant T (MAIT) cells and Vα7.2+CD161- T-cell frequency/function and their possible associations with MT and gut dysbiosis, in chronic HIV and/or HCV infections. We enrolled 56 virally infected (VI) patients (pts): 13 HIV+ on suppressive cART (HIV-RNA < 40cp/ml), 13 HCV+ naive to DAA (direct-acting antiviral) anti-HCV agents; 30 HCV+/HIV+ on suppressive cART and naive to anti-HCV. 13 age-matched healthy controls (HC) were enrolled. For Vα7.2+CD161++ and Vα7.2+CD161-CD8+ T cells we assessed: activation (CD69), exhaustion (PD1/CD39), and cytolytic activity (granzymeB/perforin). Following PMA/ionomycin and Escherichia coli stimulation we measured intracellular IL17/TNFα/IFNγ. Markers of microbial translocation (Plasma LPS, 16S rDNA, EndoCAb and I-FABP) were quantified. In 5 patients per group we assessed stool microbiota composition by 16S targeted metagenomics sequencing (alpha/beta diversity, relative abundance). Compared to controls, virally infected pts displayed significantly lower circulating Vα7.2+CD161++CD8+ MAIT cells (p = 0.001), yet expressed higher perforin (p = 0.004) and granzyme B (p = 0.002) on CD8+ MAIT cells. Upon E. coli stimulation, the residual MAIT cells are less functional particularly those from HIV+/HCV+ patients. Conversely, in virally infected pts, Vα7.2+CD161-CD8+ cells were comparable in frequency, highly activated/exhausted (CD69+: p = 0.002; PD-1+: p = 0.030) and with cytolytic potential (perforin+: p < 0.0001), yet were poorly responsive to ex vivo stimulation. A profound gut dysbiosis characterized virally infected pts, especially HCV+/HIV+ co-infected patients, delineating a Firmicutes-poor/Bacteroidetes-rich microbiota, with significant associations with MAIT cell frequency/function. Irrespective of mono/dual infection, HIV+ and HCV+ patients display depleted, yet activated/cytolytic MAIT cells with reduced ex vivo function, suggesting an impoverished pool, possibly due to continuous bacterial challenge. The MAIT cell ability to respond to bacterial stimulation correlates with the presence of Firmicutes and Bacteroidetes, possibly suggesting an association between gut dysbiosis and MAIT cell function and posing viral-mediated dysbiosis as a potential key player in the hampered anti-bacterial MAIT ability.

Dataset Information

Airway CD8+CD161++TCRv?7.2+ T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells.

Publications

Airway CD8<sup>+</sup>CD161<sup>++</sup>TCRvα7.2<sup>+</sup> T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells.

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