T cell receptor analysis in oral lichen planus

口腔扁平苔藓（OLP）是一种难治性口腔黏膜疾病，通过T细胞介导的免疫过程发展而来。在这里，我们从T细胞受体（TCR）谱、T细胞克隆性、T细胞表型和细胞因子产生谱等方面研究了浸润T细胞的特征。使用pbmc和12例OLP活检组织标本进行TCR库分析和CDR3大小谱分型。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。测定10例患者OLP组织中4种egfr样受体和6种egfr样配体的表达，并与10例健康供体正常口腔黏膜（NOM）的表达水平进行比较。我们观察到在OLP患者的组织样本（TCRVA8-1、VA22-1、VB2-1、VB3-1和VB5-1）和PBMCs （TCRVA8-1、VB2-1、VB3-1和VB5-1）中存在偏曲的TCR谱。此外，CDR3在偏态TCR亚家族中的分布呈现多克隆模式。我们观察到OLP组织标本中CD4+T淋巴细胞、IL-5、TNF-a和人白细胞抗原d相关增高。在这些受体中，只有EGFR mRNA和蛋白在OLP组织中的表达高于NOM组织。配体方面，双调节蛋白（AREG）、表调节蛋白（EREG）和肝素结合egf样生长因子（HB-EGF） mrna在OLP中的表达高于NOM组织。免疫组织化学显示，这些配体在OLP病变中通过浸润的固有层淋巴细胞和上皮角质形成细胞强烈表达。综上所述，目前的结果表明，携带这些tcr的T细胞参与了OLP的发病机制，IL-5和TNF-a可能参与了OLP的炎症过程。OLP病变中角化细胞中EGFR表达的增强以及角化细胞和浸润性单核细胞中egf样配体的上调可能参与OLP的癌变和发病机制。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