title: Recruitment of antigen-specific Th1-like responses to the human lung following bronchoscopic segmental challenge with purified protein derivative of Mycobacterium tuberculosis.
abstract: Although the mechanisms of specific immunity to Mycobacterium tuberculosis in humans are poorly understood, responses of Th1-like CD4+ T cells appear to be essential for protection. We hypothesized that healthy individuals displaying positive skin-test responses to purified protein derivative of M. tuberculosis (PPD) would have the capacity to mobilize M. tuberculosis-specific Th1 cells to the lung in response to bronchoscopic challenge with PPD. Local instillation of 0.5 tuberculin units of PPD was followed 48 h subsequently by bronchoalveolar lavage (BAL) of PPD-challenged and control segments. In PPD-positive subjects, PPD challenge resulted in a 2.7-fold increase in total BAL cells and in an increase in the percentage of lymphocytes in BAL from 10 to 19%. The BAL lymphocytosis observed in PPD-challenged segments was characterized by an increased percentage of CD4+ T cells and by increased numbers of cells capable of antigen-specific interferon-gamma production. In contrast, PPD-negative subjects did not develop local inflammation following PPD challenge. These findings indicate that bronchoscopic challenge with PPD results in recruitment of antigen-specific recall responses to the lung. This novel approach may be useful in clarifying the basis of local immunity against M. tuberculosis, and could serve more generally as a model of the development of Th1-like responses in the human lung.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4984. rfs4@po.cwru.edu
authors.forename: Richard F
authors.initials: RF
authors.lastname: Silver
authors.forename: Lynn
authors.initials: L
authors.lastname: Zukowski
authors.forename: Susan
authors.initials: S
authors.lastname: Kotake
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Fatima
authors.initials: F
authors.lastname: Pozuelo
authors.forename: Adriana
authors.initials: A
authors.lastname: Krywiak
authors.forename: Rhonda
authors.initials: R
authors.lastname: Larkin
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007159:Immunologic Tests; D007322:Instillation, Drug; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced / Q000276:immunology; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014373:Tuberculin / Q000008:administration & dosage* / Q000276:immunology; D014374:Tuberculin Test
chemical_list: D001426:Bacterial Proteins; D000939:Epitopes; D014373:Tuberculin; D007371:Interferon-gamma