Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
J Dermatol Sci. 2013 Jan;69(1):54-60. doi: 10.1016/j.jdermsci.2012.10.003. Epub 2012 Oct 17.
Systemic sclerosis (SSc) is a systemic inflammatory and fibrotic disease characterized by activation of circulating T lymphocytes.
To determine phenotypic abnormalities of γ/δ T cells and whether γ/δ T cells influence fibroblasts activation in SSc patients.
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.
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.
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.
系统性硬化症（SSc）是一种以循环 T 淋巴细胞激活为特征的系统性炎症和纤维化疾病。
确定γ/δ T 细胞的表型异常，以及γ/δ T 细胞是否影响 SSc 患者成纤维细胞的激活。
通过流式细胞术评估外周血γ/δ T 淋巴细胞的数量和比例及其表面分子的表达。分离γ/δ T 细胞与成纤维细胞共培养，实时 RT-PCR 分析成纤维细胞胶原前α1（I）和胶原前α2（I）（COL1A2）的 mRNA 表达。组织病理学检查皮肤中γ/δ T 细胞的浸润。
与健康对照者（HCs）相比，SSc 患者γ/δ T 细胞的数量和比例无显著差异。与 HCs 相比，弥漫性皮肤 SSc（dcSSc）患者γ/δ T 细胞的 CD16 和 CD69 的几何平均荧光强度（GMFI）显著增加。dcSSc 患者 CD62L 的表达明显低于 HCs。与 HCs 相比，SSc 患者 CD69 阳性γ/δ T 细胞的百分比明显更高。成纤维细胞与 SSc 来源的γ/δ T 细胞共培养时 COL1A2 mRNA 的表达明显高于与 HCs 来源的γ/δ T 细胞共培养时的表达，且这种作用不依赖于细胞间接触。此外，在 SSc 患者的皮肤中观察到γ/δ T 细胞浸润。
我们的研究结果表明，γ/δ T 细胞在 SSc 中表现出激活表型，并提示 SSc γ/δ T 细胞可能通过上调成纤维细胞 COL1A2 mRNA 的表达在纤维化过程中发挥重要作用。
