Parel Yann, Aurrand-Lions Michel, Scheja Agneta, Dayer Jean-Michel, Roosnek Eddy, Chizzolini Carlo
Geneva University Hospital, and Geneva University School of Medicine, Geneva, Switzerland.
Arthritis Rheum. 2007 Oct;56(10):3459-67. doi: 10.1002/art.22927.
Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin.
We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo.
A distinct subset expressing both CD4 and CD8alpha/beta coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo.
The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.
系统性硬化症（SSc）患者出现纤维化皮肤改变之前，会先出现富含T细胞的炎性浸润。由于此前未对正常皮肤中的T细胞进行直接比较，因此开展本研究以从功能上对早期活动性SSc患者皮肤和正常皮肤中的T细胞进行特征描述。
我们对从6例SSc患者和4名健康个体的皮肤活检标本中建立的T细胞系和克隆的共受体表达、T细胞受体（TCR）使用情况、细胞因子产生以及辅助和溶细胞活性进行了特征描述。对皮肤活检和外周血样本进行免疫荧光分析，以确认体内特定亚群的存在。
SSc和正常皮肤的T细胞系中均存在一个高水平表达CD4和CD8α/β共受体的独特亚群（双阳性[DP]）。DP T细胞可积极转录两种辅助分子，发挥克隆性分布的溶细胞和辅助活性，并表达与CD4+或CD8+单阳性（SP）T细胞不同的TCR克隆型。在SSc皮肤中，与CD4+ SP T细胞相比，DP T细胞产生的白细胞介素-4（IL-4）水平非常高。此外，在SSc皮肤中直接鉴定出了DP T细胞，从而证明它们在体内是一个独特的亚群。
目前的研究结果表明，具有不寻常CD4+CD8+ DP表型的T细胞存在于皮肤中。它们在早期活动性SSc中产生的IL-4水平非常高，这可能有助于成纤维细胞增强细胞外基质沉积。
