title: CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea.
  
  
  METHODS
  Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale.
  
  
  RESULTS
  Elastase positive cells accounted for the 7.04% +/- 1.1 of total cells, CD68+ cells for the 16.6% +/- 2, CD3+ TLs for the 28.8% +/- 7, CD4+ TLs for the 14.5 +/- 4 and CD8+ TLs for the 13.8 +/- 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01).
  
  
  CONCLUSIONS
  In UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.
authors.affiliation: Department of Critical Care and Pulmonary Services, National and Capodistrian University of Athens, Evangelismos Hospital, Athens, Greece. zdaniil@med.uth.gr
authors.forename: Zoe
authors.initials: Z
authors.lastname: Daniil
authors.forename: Panagiota
authors.initials: P
authors.lastname: Kitsanta
authors.forename: George
authors.initials: G
authors.lastname: Kapotsis
authors.forename: Maria
authors.initials: M
authors.lastname: Mathioudaki
authors.forename: Androniki
authors.initials: A
authors.lastname: Kollintza
authors.forename: Marilena
authors.initials: M
authors.lastname: Karatza
authors.forename: Joseph
authors.initials: J
authors.lastname: Milic-Emili
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Papiris
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D004417:Dyspnea / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology*; D012720:Severity of Illness Index