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

Background: Systemic sclerosis (SSc) is a systemic inflammatory and fibrotic disease characterized by activation of circulating T lymphocytes. Objective: To determine phenotypic abnormalities of gamma/delta T cells and whether gamma/delta T cells influence fibroblasts activation in SSc patients. Methods: Number and proportion of peripheral gamma/delta T lymphocytes, and their expressions of cell surface molecules were evaluated by flow cytometry. Isolated gamma/delta T cells were cocultured with fibroblast, and mRNA expressions of proalphal (I) collagen and proalpha2(I) collagen (COL1A2) of fibroblasts were analyzed by real time RT-PCR. gamma/delta T cell infiltrations in the skin were examined histopathologically. Results: No significant difference in number and proportion of gamma/delta T cells was observed in SSc patients compared to healthy controls (HCs). Geometric mean fluorescence intensity (GMFI) of CD16 and CD69 on gamma/delta 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 gamma/delta T cells was significantly higher in patients with SSc than HCs. COL1A2 mRNA expression was significantly higher in fibroblasts cocultured with gamma/delta T cells from SSc than that from HCs in cell contact independent manner. Additionally, gamma/delta T cell infiltrations were observed in SSc patients' skin. Conclusion: Our results suggest that gamma/delta T cells showed activated phenotype in SSc and suggest that SSc gamma/delta T cells may play an important role on fibrotic process by upregulation of COL1A2 mRNA expression in fibroblasts. (C) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.