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Human Immunodeficiency Virus Infection Impairs Th1 and Th17 Mycobacterium tuberculosis-Specific T-Cell Responses.


ABSTRACT: Background:Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods:Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated. Using a whole-blood flow cytometry assay, we measured expression of interferon gamma, tumor necrosis factor alpha, interleukin 2, and interleukin 17 in CD4+ and CD8+ T cells in response to Mtb antigens (PPD, ESAT-6/CFP-10 [EC], and DosR regulon-encoded ?-crystallin [Rv2031c]). Results:Fewer HIV-infected individuals had detectable CD4+ and CD8+ T-cell responses to PPD and Rv2031c than HIV-uninfected subjects. Mtb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions:HIV-associated impairment of CD4+ and CD8+Mtb-specific T-cell responses is antigen specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T-cell subset may be key to TB susceptibility in HIV-infected individuals.

SUBMITTER: Murray LW 

PROVIDER: S-EPMC5951287 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Human Immunodeficiency Virus Infection Impairs Th1 and Th17 Mycobacterium tuberculosis-Specific T-Cell Responses.

Murray Lyle W LW   Satti Iman I   Meyerowitz Jodi J   Jones Matthew M   Willberg Christian B CB   Ussher James E JE   Goedhals Dominique D   Hurst Jacob J   Phillips Rodney E RE   McShane Helen H   Vuuren Cloete van CV   Frater John J  

The Journal of infectious diseases 20180501 11


<h4>Background</h4>Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk.<h4>Methods</h4>Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemi  ...[more]

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