Pulmonary Mononuclear Cell Responses to Antigens ofMycobacterium tuberculosisin Healthy Household Contacts of Patients with Active Tuberculosis and Healthy Controls from the Community

Abstract

Protective immunity against Mycobacterium tuberculosis requires CD4+ lymphocyte-mediated immune responses and IFN-γ activity. As the primary portal of entry of M. tuberculosis is the lung, pulmonary immune responses against multiple M. tuberculosis Ags were compared between both M. tuberculosis-exposed tuberculin skin test-positive healthy household contacts (HHC) of patients with active sputum smear and culture-positive tuberculosis and tuberculin skin test-positive healthy control individuals from the community (CC). Frequencies of M. tuberculosis Ag-specific IFN-γ-producing cells, IFN-γ concentrations in culture supernatants, and DNA synthesis in bronchoalveolar cells (BAC) and PBMC were studied in HHC (n = 10) and CC (n = 15). Using enzyme-linked immunospot assay we found higher frequencies of IFN-γ-producing cells with specificity to M. tuberculosis-secreted Ag 85 (Ag 85) in BAC from HHC than in BAC from CC (p < 0.022) and relative to autologous PBMC, indicating compartmentalization of Ag 85-specific cells to the lungs. Further, IFN-γ-producing cells with specificity to components A and B of Ag 85 were specifically compartmentalized to the lungs in HHC (p < 0.05). IFN-γ concentrations in culture supernatants of BAC and Ag-specific DNA synthesis were low and comparable in the two subject groups. Increased immune responses to Ag 85 at the site of repeated exposure to M. tuberculosis (the lung) may represent an important component of protective immunity against M. tuberculosis. Correlates of protective immunity against M. tuberculosis are required for assessment of the efficiency of anti-tuberculous vaccines.

Highly Focused T Cell Responses in Latent Human Pulmonary Mycobacterium tuberculosis Infection

“…Several studies report a prominence of Th2-type cytokines, e.g., IL-10 (25-27), in PBL. In contrast, T cells from other compartments in patients with active TB, such as pleural effusions (28,29) or T cells isolated by bronchoalveolar lavage (30,31), showed a marked IFN-␥ and/or proliferative response that was lower or even absent in PBL of the same analyzed patients. This phenomenon may be due to sequestration of distinctive MTB-reactive T cells to the site of infection, possibly on account of particular chemokine receptors, such as CCR2 or CCR5 (32).…”

Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease

“…The gene expression in cells in the peripheral blood may not reflect the gene expression response in the lung, which is the actual site of NTM infection. Peripheral blood monocytes can reflect the immunoreactivity of airway cells, but the immune response of peripheral blood monocytes may be confounded due to a lack of local immunoregulatory mechanisms present in the lung [29,30]. Therefore, further studies involving TLR2 mRNA expression and subsequent cytokine immune responses using bronchoalveolar lavage cells or lung tissue are needed.…”

Tuberculosis Is Associated with a Down-Modulatory Lung Immune Response That Impairs Th1-Type Immunity

“…Most studies have relied on murine models (3,4), in vitro M. tuberculosis Ag-rechallenged ex vivo human BAL cells, peripheral blood from TB patients and their contacts (41,42), or BAL cells from patients with TB pleurisy (42). Few studies have comprehensively evaluated the immune profiles of lung cells from active TB patients during treatment (8).…”