Pulmonary Mycobacterium tuberculosis control associates with CXCR3- and CCR6-expressing antigen-specific Th1 and Th17 cell recruitment

JCI Insight. 2020 Jul 23;5(14):e137858. doi: 10.1172/jci.insight.137858.


Mycobacterium tuberculosis-specific (M. tuberculosis-specific) T cell responses associated with immune control during asymptomatic latent tuberculosis infection (LTBI) remain poorly understood. Using a nonhuman primate aerosol model, we studied the kinetics, phenotypes, and functions of M. tuberculosis antigen-specific T cells in peripheral and lung compartments of M. tuberculosis-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage, for up to 24 weeks postinfection. We found substantially higher frequencies of M. tuberculosis-specific effector and memory CD4+ and CD8+ T cells producing IFN-γ in the airways compared with peripheral blood, and these frequencies were maintained throughout the study period. Moreover, M. tuberculosis-specific IL-17+ and IL-17+IFN-γ+ double-positive T cells were present in the airways but were largely absent in the periphery, suggesting that balanced mucosal Th1/Th17 responses are associated with LTBI. The majority of M. tuberculosis-specific CD4+ T cells that homed to the airways expressed the chemokine receptor CXCR3 and coexpressed CCR6. Notably, CXCR3+CD4+ cells were found in granulomatous and nongranulomatous regions of the lung and inversely correlated with M. tuberculosis burden. Our findings provide insights into antigen-specific T cell responses associated with asymptomatic M. tuberculosis infection that are relevant for developing better strategies to control TB.

Keywords: Immunology; Infectious disease; Tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / microbiology
  • Disease Models, Animal
  • Female
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Latent Tuberculosis / genetics*
  • Latent Tuberculosis / immunology
  • Latent Tuberculosis / microbiology
  • Latent Tuberculosis / pathology
  • Lung / immunology*
  • Lung / microbiology
  • Lung / pathology
  • Macaca mulatta
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Receptors, CCR6 / genetics*
  • Receptors, CXCR3 / genetics*
  • Th1 Cells / immunology
  • Th1 Cells / microbiology
  • Th17 Cells / immunology
  • Th17 Cells / microbiology
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology


  • Antigens, Bacterial
  • Interleukin-17
  • Receptors, CCR6
  • Receptors, CXCR3