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*
Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106;
Department of Microbiology, National Institute of Respiratory Diseases, Mexico City, Mexico;
Bronchoscopy Service, National Institute of Respiratory Diseases, Mexico City, Mexico;
§
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106; and
¶
Department of Tuberculosis Immunology, Statens Serum Institute, Copenhagen, Denmark
Protective immunity against Mycobacterium
tuberculosis requires CD4+ lymphocyte-mediated
immune responses and IFN-
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--producing cells, IFN- 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--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--producing cells with specificity
to components A and B of Ag 85 were specifically compartmentalized to
the lungs in HHC (p < 0.05). IFN-
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.
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