title: Presence of activated airway T lymphocytes in human puumala hantavirus disease.
abstract: BACKGROUND
  Hantaviruses cause two clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information about the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways.
  
  
  METHODS
  Bronchoscopy was performed in 15 hospitalized patients with HFRS, with sampling of endobronchial mucosal biopsies and BAL fluid. Biopsies were stained for leukocytes, lymphocyte subsets, and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as a control group.
  
  
  RESULTS
  Compared with control subjects, endobronchial mucosal biopsies from patients with HFRS revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (P ≤ .001), along with an increase in submucosal CD4(+) T cells (P = .001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (P < .001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in patients with HFRS (P < .001). In patients with HFRS, analyses of T-cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (P = .011 and P = .025) and natural killer cells (P < .001), together with an increased expression of activation markers human leukocyte antigen-DR (HLA-DR) and CD25 on T cells (P < .001 and P < .001).
  
  
  CONCLUSIONS
  The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.
authors: Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden. Electronic address: johan.rasmuson@climi.umu.se.
authors: Johan
authors: J
authors: Rasmuson
authors: Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Jamshid
authors: J
authors: Pourazar
authors: Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Mats
authors: M
authors: Linderholm
authors: Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Thomas
authors: T
authors: Sandström
authors: Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Anders
authors: A
authors: Blomberg
authors: Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
authors: Clas
authors: C
authors: Ahlm
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D018804:Hantavirus Pulmonary Syndrome / Q000276:immunology; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029262:Puumala virus; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: D019010:Vascular Cell Adhesion Molecule-1