Circulating γ/δ T cells in systemic sclerosis exhibit activated phenotype and enhance gene expression of proalpha2(I) collagen of fibroblasts

J Dermatol Sci. 2013 Jan;69(1):54-60. doi: 10.1016/j.jdermsci.2012.10.003. Epub 2012 Oct 17.

Abstract

Background: Systemic sclerosis (SSc) is a systemic inflammatory and fibrotic disease characterized by activation of circulating T lymphocytes.

Objective: To determine phenotypic abnormalities of γ/δ T cells and whether γ/δ T cells influence fibroblasts activation in SSc patients.

Methods: Number and proportion of peripheral γ/δ T lymphocytes, and their expressions of cell surface molecules were evaluated by flow cytometry. Isolated γ/δ T cells were cocultured with fibroblast, and mRNA expressions of proalpha1(I) collagen and proalpha2(I) collagen (COL1A2) of fibroblasts were analyzed by real time RT-PCR. γ/δ T cell infiltrations in the skin were examined histopathologically.

Results: No significant difference in number and proportion of γ/δ T cells was observed in SSc patients compared to healthy controls (HCs). Geometric mean fluorescence intensity (GMFI) of CD16 and CD69 on γ/δ T cells was significantly increased in patients with diffuse cutaneous SSc (dcSSc) compared to HCs. CD62L expression was significantly decreased in patients with dcSSc compared to HCs. The percentage of CD69 positive γ/δ T cells was significantly higher in patients with SSc than HCs. COL1A2 mRNA expression was significantly higher in fibroblasts cocultured with γ/δ T cells from SSc than that from HCs in cell contact independent manner. Additionally, γ/δ T cell infiltrations were observed in SSc patients' skin.

Conclusion: Our results suggest that γ/δ T cells showed activated phenotype in SSc and suggest that SSc γ/δ T cells may play an important role on fibrotic process by upregulation of COL1A2 mRNA expression in fibroblasts.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Coculture Techniques
  • Collagen Type I / biosynthesis*
  • Collagen Type I / genetics*
  • Female
  • Fibroblasts / metabolism*
  • Fibrosis / genetics
  • Humans
  • L-Selectin / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Phenotype
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgG / metabolism
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / pathology*
  • Statistics, Nonparametric
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Collagen Type I
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgG
  • L-Selectin