Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa

Abstract

Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous ΔF508+/+CF patients versus non‐CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non‐CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0·001). The number of T lymphocytes was higher at the CF distal level (P = 0·035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0·033) in the CF surface epithelium, which overexpressed ICAM‐1 but not VCAM‐1 and E‐selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.

Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse model

“…Specifically, the B6 and BALB CF strains were shown to differ in the expression of lymphocyte activation genes, among other genes of their expression profiles, in response to nonfunctional Cftr, and a strain-dependent difference in T lymphocyte influx was evident. T cell and B cell aggregates have been reported by Hubeau et al (11) as part of the clinical CF lung disease course, and this airway leukocyte trafficking was proposed by Moss (23) to influence the earliest stages of inflammatory CF lung disease.…”

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

“…Lymphocytes express CFTR and therefore may be affected by defects in this channel (26,(52)(53)(54)(55)(56). Lymphocytes are also present in sizable aggregates within the subepithelial space of the CF airway (6), positioning them to function as important regulators of airway inflammation. It is clear that the immune response contributes to the overall CF disease pathogenesis, but few studies have approached this aspect directly.…”

“…Neutrophils are the major cell type within the CF airway but both B and T lymphocytes are found in large aggregates beneath the surface epithelium (5,6). In infants with CF, exaggerated production of proinflammatory cytokines is observed in lower airways (7,8), yet the majority of CF patients will eventually become colonized with Pseudomonas aeruginosa and complete eradication of this organism is uncommon (9).…”

ICAM‐1 expression on conjunctival epithelial cells in patients with cystic fibrosis

“…We studied 24 patients with CF (female(F)/ male (M): 13/11) with a mean age of 14.32 6 3.91 years (range [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] presented to the III Department of Pediatric Diseases, Medical University of Bialystok, Poland. Twenty-four normal subjects (F/M: 12/12) with a mean age 13.92 6 3.32 (range 8-21) were also included.…”