Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions
Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions
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DOI：
10.1046/j.0022-202x.2001.01548.x
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发表时间：
2001-12-01
影响因子：
6.5
通讯作者：
Tomkinson, B
中科院分区：
文献类型：
--
作者：
Lin, WJ;Norris, DA;Tomkinson, B
CD8(+) T细胞浸润到表皮被认为是银屑病发病的一个关键事件。采用定量竞争性聚合酶链反应方法检测银屑病皮损表皮中T细胞受体β链可变区2、3、6.1-3、8和13.1基因的表达。对5例银屑病患者的表皮样本和外周血样本进行了配对研究。结果显示T细胞受体β链可变区3（2例）、8（2例）和/或2（1例）扩增。与先前的报道相反，β链可变区6.1-3和β链可变区13.1亚群在任何病变中均未扩大。DNA序列分析显示，在所有扩展β链可变区家族中均观察到优势T细胞克隆，而在非扩展β链可变区家族中观察到异质群体和/或小克隆。利用CDR3长度分析检查病变表皮浸润性T细胞的完整β链库，我们发现每个患者病变中约50%的T细胞受体β链可变区家族表现出异常的CDR3 DNA长度分布，表明存在单克隆或少克隆T细胞扩增。综上所述，结果表明，在不同的患者中，T细胞低克隆性并不局限于有限数量的T细胞受体β链可变区家族。为了在病变中许多扩增的T细胞克隆中识别致病T细胞，我们比较了病变表皮和非病变表皮中T细胞受体的扩增。特定的T细胞受体在病变表皮中被发现优先扩增，这些病变特异性T细胞克隆可能在银屑病病变的发病和发展中最重要。
CD8(+) T cell infiltration into the epidermis is thought to be a key event in the pathogenesis of psoriasis. A quantitative competitive polymerase chain reaction method was developed to examine the expression of T cell receptor beta chain variable region 2, 3, 6.1-3, 8, and 13.1 genes in the epidermis of psoriatic lesions. Paired epidermal samples and peripheral blood samples from five psoriasis patients were studied. The results demonstrated the expansion of T cell receptor beta chain variable region 3 (two patients), 8 (two patients), and/or 2 (one patient). Contrary to previous reports, neither beta chain variable region 6.1-3 nor beta chain variable region 13.1 subgroups were expanded in any of the lesions. DNA sequence analysis revealed dominant T cell clones observed in all expanded beta chain variable region families and heterogeneous populations and/or small clones observed in nonexpanded beta chain variable region families. Using CDR3 length analysis to examine the complete beta chain repertoire of the infiltrating T cells in the lesional epidermis, we found that approximately 50% of the T cell receptor beta chain variable region families in each patient's lesion demonstrated abnormal CDR3 DNA length distribution, indicating the presence of monoclonal or oligoclonal T cell expansion. Together, the results show that among different patients, T cell oligoclonality is not restricted to a limited number of T cell receptor beta chain variable region families. In an attempt to identify the pathogenic T cells among the many expanded T cell clones in the lesions, we compared T cell receptor expansion in the lesional epidermis with nonlesional epidermis. Particular T cell receptor were found to be preferentially expanded in lesional epidermis and these lesion-specific T cell clones may be most important in the pathogenesis and development of psoriatic lesions.