Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients

Irina G. Luzina, Sergei P. Atamas, Robert A Wise, Fredrick Wigley, Jung Choi, Huiqing Xiao, Barbara White

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2262-2274
Number of pages13
JournalArthritis and Rheumatism
Volume48
Issue number8
DOIs
StatePublished - Aug 1 2003

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T-Lymphocytes
Gene Expression
Lung
Pulmonary Fibrosis
Transforming Growth Factors
Pneumonia
Healthy Volunteers
Oncostatin M
Phenotype
Bronchoalveolar Lavage Fluid
Oligonucleotide Array Sequence Analysis
Matrix Metalloproteinases
Transcriptome
Integrins
Interleukin-4
Lung Diseases
Cluster Analysis
Real-Time Polymerase Chain Reaction
Cause of Death
Fibrosis

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. / Luzina, Irina G.; Atamas, Sergei P.; Wise, Robert A; Wigley, Fredrick; Choi, Jung; Xiao, Huiqing; White, Barbara.

In: Arthritis and Rheumatism, Vol. 48, No. 8, 01.08.2003, p. 2262-2274.

Research output: Contribution to journalArticle

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