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T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR Vα-Vβ genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption

机译:T细胞受体(TCR)的组成和人类表皮T细胞的功能:受限制的TCRVα-Vβ基因被固定在药疹中的病变表皮中的T细胞利用

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摘要

Human epidermis contains a phenotypically heterogeneous population of T cells. No information, however, is available regarding the TCR repertoire of these T cells and their relevant physiologic and pathologic functions in vivo. To this end, T cells were prepared from the lesional epidermis in two patients with fixed drug eruption (FDE) and their phenotype, function and TCR repertoire were examined in parallel. Both epidermal T cells, termed FDE-1 and -2 cells, respectively, expressed αβ TCR, but displayed some phenotypic heterogeneity. These T cells were induced to display cytolytic activity by ligation of the CD3/TCR-αβ complex. Comparative analyses of TCR Vα and Vβ expression in the epidermal T cells and the paired peripheral blood lymphocytes (PBL) by quantitative polymerase chain reaction (PCR) demonstrated that the epidermal T cells, but not the paired PBL, utilized a very limited range of Vα and Vβ genes. These results indicate that some expansion or preferential migration of epidermal T cells that recognize a restricted set of antigens expressed within the epidermis could occur in situ following ingestion of the causative drug. The persistence of these epidermal T cells in FDE lesions suggests their pathologic role in a drug-induced flare.
机译:人表皮含有表型异质性的T细胞群。然而,没有关于这些T细胞的TCR库及其在体内的相关生理和病理功能的信息。为此,从两名患有固定药疹(FDE)的患者的病灶表皮中制备了T细胞,并对其表型,功能和TCR库进行了平行检查。这两种表皮T细胞分别称为FDE-1和-2细胞,均表达αβTCR,但表现出某些表型异质性。通过连接CD3 /TCR-αβ复合物,诱导这些T细胞显示出细胞溶解活性。通过定量聚合酶链反应(PCR)对TCRVα和Vβ在表皮T细胞和成对的外周血淋巴细胞(PBL)中的比较分析表明,表皮T细胞而不是成对的PBL利用非常有限的Vα范围和Vβ基因。这些结果表明,摄入致病药物后,表皮T细胞的某些扩增或优先迁移可能识别表皮内表达的一组有限抗原,这可能会在原位发生。这些表皮T细胞在FDE病变中的持久性表明它们在药物诱发的耀斑中的病理作用。

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