Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts

Am J Respir Crit Care Med. 2006 Jan 15;173(2):238-45. doi: 10.1164/rccm.200503-411OC. Epub 2005 Oct 6.


Rationale: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity.

Objectives: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs).

Methods: AMs were infected with Mtb strains H(37)Ra and H(37)Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7.

Main results: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p < 0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-gamma, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-gamma production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p < 0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-gamma and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p < 0.05).

Conclusion: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • Cells, Cultured / immunology
  • Cells, Cultured / microbiology
  • Coculture Techniques / methods
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Lung / immunology*
  • Macrophage Activation / immunology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / microbiology*
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / immunology*
  • Nitric Oxide / immunology
  • Reference Values
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / microbiology
  • Time Factors
  • Tuberculosis / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Interferon-gamma