title: Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis.
abstract: BACKGROUND
  Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve, whereas patients with chronic disease often progress to fibrosis. However, the mechanisms underlying this difference are unknown.
  
  
  OBJECTIVE
  To examine the T-cell profile from patients with subacute HP and chronic HP.
  
  
  METHODS
  T cells were obtained by bronchoalveolar lavage from 25 patients with subacute HP, 30 patients with chronic HP, and 8 control subjects. T-cell phenotype and functional profile were evaluated by flow cytometry, cytometric bead array, and immunohistochemistry.
  
  
  RESULTS
  Patients with chronic HP showed higher CD4+:CD8+ ratio (median, 3.05; range, 0.3-15; subacute HP: median, 1.3; range, 0.1-10; control: median, 1.3; range, 0.7-2.0; P < 0.01), and a decrease of gammadeltaT cells (median, 2.0; range, 0.5-3.4; subacute HP: median, 10; range, 4.8-17; control: median, 15; range, 5-19; P < 0.01). Patients with chronic HP exhibited an increase in the terminally differentiated memory CD4+ and CD8+ T-cell subsets compared with patients with subacute HP (P < 0.05). However, memory cells from chronic HP showed lower IFN-gamma production and decreased cytotoxic activity by CD8+ T lymphocytes. Chronic HP displayed a Th2-like phenotype with increased CXCR4 expression (median, 6%; range, 1.7-36, vs. control subjects: median, 0.7%; range, 0.2-1.4; and subacute HP: median, 2.2%; range, 0.1-5.3; P < 0.01), and decreased CXCR3 expression (median, 4.3%; range, 1.4-25%, vs. subacute HP: median, 37%; range, 4.9-78%; P < 0.01). Likewise, supernatants from antigen-specific-stimulated cells from chronic HP produced higher levels of IL-4 (80 +/- 63 pg/ml vs. 25 +/- 7 pg/ml; P < 0.01), and lower levels of IFN-gamma (3,818 +/- 1671 pg/ml vs. 100 +/- 61 pg/ml; P < 0.01) compared with subacute HP.
  
  
  CONCLUSIONS
  Our findings indicate that patients with chronic HP lose effector T-cell function and exhibit skewing toward Th2 activity, which may be implicated in the fibrotic response that characterizes this clinical form.
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, Mexico DF, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Barrera
authors.forename: Felipe
authors.initials: F
authors.lastname: Mendoza
authors.forename: Joaquín
authors.initials: J
authors.lastname: Zuñiga
authors.forename: Andrea
authors.initials: A
authors.lastname: Estrada
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zamora
authors.forename: Emma I
authors.initials: EI
authors.lastname: Melendro
authors.forename: Remedios
authors.initials: R
authors.lastname: Ramírez
authors.forename: Annie
authors.initials: A
authors.lastname: Pardo
authors.forename: Moisés
authors.initials: M
authors.lastname: Selman
mesh_terms: D000328:Adult; D000368:Aged; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016516:CD4-CD8 Ratio; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2