Effect of HIV on the Frequency and Number of Mycobacterium tuberculosis-Specific CD4+ T Cells in Blood and Airways During Latent M. Tuberculosis Infection

J Infect Dis. 2017 Dec 19;216(12):1550-1560. doi: 10.1093/infdis/jix529.

Abstract

Human immunodeficiency virus type 1 (HIV) infection substantially increases the risk of developing tuberculosis. There is extensive depletion of Mycobacterium tuberculosis-specific CD4+ T cells in blood during early HIV infection, but little is known about responses in the lungs at this stage. Given that mucosal organs are a principal target for HIV-mediated CD4+ T-cell destruction, we investigated M. tuberculosis-specific responses in bronchoalveolar lavage (BAL) from persons with latent M. tuberculosis infection and untreated HIV coinfection with preserved CD4+ T-cell counts. M. tuberculosis-specific CD4+ T-cell cytokine (interferon γ, tumor necrosis factor α, and interleukin 2) responses were discordant in frequency and function between BAL and blood. Responses in BAL were 15-fold lower in HIV-infected persons as compared to uninfected persons (P = .048), whereas blood responses were 2-fold lower (P = .006). However, an increase in T cells in the airways in HIV-infected persons resulted in the overall number of M. tuberculosis-specific CD4+ T cells in BAL being similar. Our study highlights the important insights gained from studying M. tuberculosis immunity at the site of disease during HIV infection.

Keywords: CD4+ T-cell responses; Human immunodeficiency virus; Mycobacterium tuberculosis; adaptive immunity; bronchoalveolar lavage; coinfection; lung.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Coinfection / immunology*
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Latent Tuberculosis / complications
  • Latent Tuberculosis / immunology*
  • Lung / immunology*
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • IL2 protein, human
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma