title: Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in 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-gamma 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-gamma-producing cells, IFN-gamma 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-gamma-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-gamma-producing cells with specificity to components A and B of Ag 85 were specifically compartmentalized to the lungs in HHC (p < 0. 05). IFN-gamma 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.
authors.affiliation: Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Schwander
authors.forename: M
authors.initials: M
authors.lastname: Torres
authors.forename: C
authors.initials: C
authors.lastname: Carranza C
authors.forename: D
authors.initials: D
authors.lastname: Escobedo
authors.forename: M
authors.initials: M
authors.lastname: Tary-Lehmann
authors.forename: P
authors.initials: P
authors.lastname: Anderson
authors.forename: Z
authors.initials: Z
authors.lastname: Toossi
authors.forename: J J
authors.initials: JJ
authors.lastname: Ellner
authors.forename: E A
authors.initials: EA
authors.lastname: Rich
authors.forename: E
authors.initials: E
authors.lastname: Sada
mesh_terms: D000217:Acyltransferases; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis