Abstract
Objective. Pulmonary fibrosis is a major cause of death in scleroderma patients. Previous studies have shown an increase in CD8+ T cells in the lungs of scleroderma patients. In the present study, we sought to determine whether activated CD8+ T cells contribute to pulmonary fibrosis in scleroderma patients through the production and activation of profibrotic mediators. Methods. CD8+ cells were isolated from bronchoalveolar lavage fluid obtained from 19 scleroderma patients and 7 healthy subjects. The phenotype of these cells was determined using DNA array technology. Expression of selected genes was confirmed in real-time polymerase chain reaction and enzyme-linked immunosorbent assay experiments. Results. Hierarchical clustering of gene expression profiles revealed 2 groups of subjects. Group 1 consisted of 11 patients (8 with and 3 without lung inflammation). Group 2 consisted of 15 subjects (7 healthy controls and 2 patients with and 6 without lung inflammation). Gene expression in group 1 indicated T cell activation, a type 2 phenotype, production of profibrotic factors and matrix metalloproteinases, and reduced activation -induced cell death. Increased expression of β6 integrin messenger RNA by CD8+ T cells in group 1 suggested the possibility that these T cells might induce cell-contact-dependent activation of latent transforming growth factor β (TGFβ). Conclusion. A subset of scleroderma patients at higher risk of progressive lung disease have activated, long-lived CD8+ T cells in their lungs that could promote fibrosis directly, through production of profibrotic factors such as interleukin-4 and oncostatin M, as well as indirectly, through activation of TGFβ.
Original language | English (US) |
---|---|
Pages (from-to) | 2262-2274 |
Number of pages | 13 |
Journal | Arthritis and rheumatism |
Volume | 48 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2003 |
ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
- Pharmacology (medical)