title: Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD.
abstract: BACKGROUND
  A suggested role for T cells in COPD pathogenesis is based on associations between increased lung cytotoxic T lymphocyte (CD8+) numbers and airflow limitation. CD69 is an early T cell activation marker. Natural Killer cell group 2 D (NKG2D) receptors are co-stimulatory molecules induced on CD8+ T cells upon activation. The activating function of NKG2 D is triggered by binding to MHC class 1 chain-related (MIC) molecules A and B, expressed on surface of stressed epithelial cells. The aim of this study was to evaluate the expression of MIC A and B in the bronchial epithelium and NKG2 D and CD69 on BAL lymphocytes in subjects with COPD, compared to smokers with normal lung function and healthy never-smokers.
  
  
  METHODS
  Bronchoscopy with airway lavages and endobronchial mucosal biopsy sampling was performed in 35 patients with COPD, 21 healthy never-smokers and 16 smokers with normal lung function. Biopsies were immunohistochemically stained and BAL lymphocyte subsets were determined using flow cytometry.
  
  
  RESULTS
  Epithelial CD3+ lymphocytes in bronchial biopsies were increased in both smokers with normal lung function and in COPD patients, compared to never-smokers. Epithelial CD8+ lymphocyte numbers were higher in the COPD group compared to never-smoking controls. Among gated CD3+cells in BAL, the percentage of CD8+ NKG2D+ cells was enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. The percentage of CD8+ CD69+ cells and cell surface expression of CD69 were enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. No changes in the expression of MIC A or MIC B in the airway epithelium could be detected between the groups, whereas significantly decreased soluble MICB was detected in bronchial wash from smokers with normal lung function, compared to never-smokers.
  
  
  CONCLUSIONS
  In COPD, we found increased numbers of cytotoxic T cells in both bronchial epithelium and airway lumen. Further, the proportions of CD69- and NKG2D-expressing cytotoxic T cells in BAL fluid were enhanced in both subjects with COPD and smokers with normal lung function and increased expression of CD69 was found on CD8+ cells, indicating the cigarette smoke exposure-induced expansion of activated cytotoxic T cells, which potentially can respond to stressed epithelial cells.
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Sweden. ester.roos-engstrand@lung.umu.se
authors.forename: Ester
authors.initials: E
authors.lastname: Roos-Engstrand
authors.forename: Jamshid
authors.initials: J
authors.lastname: Pourazar
authors.forename: Annelie F
authors.initials: AF
authors.lastname: Behndig
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015640:Ion Channel Gating / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis* / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism*; D012129:Respiratory Function Tests; D012907:Smoking / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000099192:CD69 Antigens