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

J Infect Dis. 2018 May 5;217(11):1782-1792. doi: 10.1093/infdis/jiy052.


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 α-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Coinfection / immunology
  • Coinfection / microbiology
  • Coinfection / virology
  • Cytokines / immunology
  • Female
  • HIV / immunology
  • HIV Infections / immunology*
  • HIV Infections / microbiology
  • Humans
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • South Africa
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Tuberculosis / virology
  • Young Adult


  • Antigens, Bacterial
  • Cytokines
  • Interferon-gamma