Drs. Luzina and Atamas contributed equally to this work.
Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients
Article first published online: 1 AUG 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 8, pages 2262–2274, August 2003
How to Cite
Luzina, I. G., Atamas, S. P., Wise, R., Wigley, F. M., Choi, J., Xiao, H. Q. and White, B. (2003), Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. Arthritis & Rheumatism, 48: 2262–2274. doi: 10.1002/art.11080
- Issue published online: 1 AUG 2003
- Article first published online: 1 AUG 2003
- Manuscript Accepted: 31 MAR 2003
- Manuscript Received: 10 JAN 2003
- NIH. Grant Number: 1R03-AR-47110
- Maryland Chapter of the Arthritis Foundation
- NIH. Grant Number: 1R01-HL-54163
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.
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.
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).
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.