Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1.

Abstract

In order to determine whether the airway inflammatory cells of chronic obstructive pulmonary disease (COPD) are different from those seen in asthma, we have studied a subepithelial zone, 100 microns deep to the epithelial reticular basement membrane in bronchial biopsies taken from five normal nonsmoking subjects without chronic bronchitis or asthma (FEV1 percentage of predicted [mean +/- SD] 105.7 +/- 25.3), 11 subjects with chronic bronchitis alone (FEV1 percentage of predicted 98.5 +/- 12.9), and 13 subjects with chronic bronchitis in whom there was also evidence of airflow limitation (i.e., COPD; FEV1 percentage of predicted 59.7 +/- 10.0). Using immunohistochemical markers, we counted distinct types of inflammatory cell and expressed them as [median and range] per mm basement membrane. When there was airflow limitation we found significantly increased numbers of CD3+ T lymphocytes (COPD 22.3 [2.6 to 68.2] versus normal 3.7 [1.5 to 16.3]; p < 0.05), an increased number of CD8+ cells (COPD 19.3 [1.8 to 45.5] versus normal 2.3 [0.9 to 4.2]; p < 0.01), and increased expression of HLA-DR (COPD versus normal; p = 0.01). There was also an increased number of CD68+ cells (i.e., macrophages) (COPD 7.4 [0.4 to 16.9] versus normal 0.7 [0 to 2.6]; p < 0.01; COPD versus chronic bronchitis alone 2.7 [0 to 12.8]; p < 0.05). There were no significant differences between the groups in the numbers of subepithelial neutrophils, mast cells, eosinophils or B lymphocytes. There were weak but significant negative associations between the CD8+ T-cell subset (r = -0.42), neutrophils (r = -0.46), and eosinophils (r = -0.53) and FEV1 percentage of predicted in all the chronic bronchitic smokers (p < 0.05). The data confirm the involvement of subepithelial T lymphocytes and macrophages in smoking-induced airflow limitation and provide novel data which support the view that COPD is distinct from asthma with respect to the predominance of the CD8+ T-cell subset in this smoking-related condition.

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

“…A recent study has demonstrated genetic control of the ratio between CD8+ and CD4+ cells with a small (5%) percentage of the population having a CD4/CD8 ratio of <1 [22]. The current data would be consistent with the hypothesis, suggested by O'SHAUGHNESSY et al [8], that those with a genetically determined increase in the CD8+ population may be more susceptible to a further increase in CD8+ cells induced by smoking. This hypothesis might also explain the overlap between the number of CD8+ve cells between the nonsmokers and the asymptomatic smokers.…”

“…Previous studies have demonstrated an increase in the number of T-cells infiltrating the large airway subepithelium and a shift towards a CD8 phenotype [3±8] in addition to increases in the number of macrophages [4,5,8]. An increase in the number of infiltrating eosinophils has been observed in the large airway subepithelium although they do not appear to be degranulated as in asthma [9].…”

“…An increase in the number of infiltrating eosinophils has been observed in the large airway subepithelium although they do not appear to be degranulated as in asthma [9]. Although studies examining bronchoalveolar lavage have demonstrated increases in the number of neutrophils in subjects with COPD [10±14] this has not been supported by the majority of studies of the large airway subepithelium [4,5,8,11].…”

αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

“…The occurrence of CD103 expressing cells in tissue could very well vary between COPD and healthy individuals. An analogous situation is the lack of significant difference in our data between the total numbers of CD8+ cells per ml of BAL fluid from COPD patients vs. healthy subjects, in spite of overwhelming evidence of an increase of CD8+ cells in tissue from COPD patients [3,6] . The difference in percentage of CD8+ T-cells that we found in our study is most probably due to increased numbers of alveolar macrophages (data not shown) in BAL from COPD patients.…”

“…The numbers of macrophages and CD8+ T-cells in the bronchial mucosa and peripheral lung tissue correlate with a decline in lung function, indicating a role for these cells in the pathogenesis of COPD [2][3][4][5][6] . Studies of tissue samples from smokers and COPD patients have shown increased numbers of CD8+ T-cells in comparison to healthy control subjects, yet few studies have described the function of the these cells.…”