T cell receptor analysis in oral lichen planus

口腔扁平苔藓（OLP）是一种难治性口腔粘膜疾病，通过T细胞介导的免疫过程发展。在这里，我们研究了浸润性T细胞的T细胞受体（TCR）库，T细胞克隆性，T细胞表型和细胞因子的生产概况方面的特点。使用来自12名患者的PBMC和OLP活检组织标本进行TCR库分析和CDR 3大小谱分析。实时定量聚合酶链反应检测细胞因子表达谱和T细胞表型。检测了10例OLP患者口腔黏膜组织中4种EGFR样受体和6种EGF样配体的表达，并与10例健康人正常口腔黏膜（NOM）进行比较。我们观察到OLP患者的组织样品（TCRVA 8 -1、VA 22 -1、VB 2 -1、VB 3 -1和VB 5 -1）和PBMC（TCRVA 8 -1、VB 2 -1、VB 3 -1和VB 5 -1）中存在偏斜的TCR谱系。此外，CDR 3在偏态TCR亚家族中的分布 ...更多信息 显示多克隆模式。我们观察到OLP组织标本中CD 4 +T淋巴细胞、IL-5、TNF-α和人类白细胞抗原D相关的增加。OLP组织中EGFR mRNA和蛋白表达均高于NOM组织。关于配体，双调蛋白（AREG），epiregulin（EREG）和肝素结合EGF样生长因子（HB-EGF）的mRNA在OLP中的表达高于NOM组织。这些配体强烈表达的浸润层固有淋巴细胞以及上皮角质形成细胞在OLP病变，如免疫组化所示。以上结果提示，携带这些TCR的T细胞参与了OLP的发病过程，IL-5和TNF-α可能参与了OLP的炎症过程，OLP皮损角质形成细胞EGFR表达增强，角质形成细胞和浸润的单个核细胞EGF样配体表达上调可能参与了OLP的发生和发病。少

Oral lichen planus (OLP) is a refractory disorder of the oral mucosa, and develops via a T cell-mediated immune process. Here, we examined the characteristics of the infiltrating T cells in terms of the T cell receptor (TCR) repertoires, T cell clonality, T cell phenotypes and cytokine production profiles. TCR repertoire analyses and CDR3 size spectratyping were performed using PBMCs and tissue specimens of OLP biopsies from 12 patients. The cytokine expression profiles and T cell phenotypes were measured by real-time quantitative polymerase chain reaction. The expressions of 4 EGFR-like receptors and 6 EGF-like ligands were measured in OLP tissues from 10 patients and compared with the levels in normal oral mucosa (NOM) from 10 healthy donors. We observed that there were skewed TCR repertoires in the tissue samples (TCRVA8-1, VA22-1, VB2-1, VB3-1 and VB5-1) and PBMCs (TCRVA8-1, VB2-1, VB3-1 and VB5-1) from OLP patients. Furthermore, the CDR3 distributions in the skewed TCR subfamilies … More exhibited polyclonal patterns. We observed increases in CD4+T lymphocytes, IL-5, TNF-a and human leucocyte antigen D-related in the OLP tissue specimens. Of the receptors, only EGFR mRNA and protein were more highly expressed in OLP compared with NOM tissues. Regarding the ligands, the mRNAs of amphiregulin (AREG), epiregulin (EREG), and heparin-binding EGF-like growth factor (HB-EGF) were more highly expressed in OLP compared with NOM tissues. These ligands were strongly expressed by infiltrating lamina propria lymphocytes as well as epithelial keratinocytes in OLP lesions, as shown by immunohistochemistry. Taken together, the present results suggest that T cells bearing these TCRs are involved in the pathogenesis of OLP, and that IL-5 and TNF-a may participate in its inflammatory process.The enhanced EGFR expression on the keratinocytes in OLP lesions and the up-regulation of EGF-like ligands in keratinocytes and infiltrating mononuclear cells could contribute to the carcinogenesis and pathogenesis of OLP. Less