Vekony M A, Holder J E, Lee A J, Horrocks C, Eperon I C, Camp R D
Division of Dermatology, University of Leicester, United Kingdom.
J Invest Dermatol. 1997 Jul;109(1):5-13. doi: 10.1111/1523-1747.ep12276303.
Several groups have investigated the role of T cells in the pathogenesis of psoriasis by determination of T-cell receptor (TCR) B-chain variable (V) region usage, both in chronic plaque (psoriasis vulgaris) and guttate forms, with various results. Because there are no data on TCR expression in early psoriasis vulgaris, when specific cellular immune events may be expected to be most pronounced, we have analyzed early lesions (less than 3 wk old) of ten patients, with highly reproducible results. We have developed a highly controlled anchored polymerase chain reaction (PCR) method in which TCR beta chain species are all amplified with the same primer pair and products are quantified by dot blot hybridization with BV family-specific oligonucleotide probes. Overexpression of certain TCR BV genes was observed in the majority of lesional biopsies, but in samples in which the expanded BV family formed more than 10% of total lesional BV (half of the samples analyzed), BV2 and BV6 predominated. The consistency of overexpression of these BV species between patients was much less than in previous studies of TCRBV usage in established chronic plaque psoriasis lesions. Complementarity-determining region 3 (CDR3) size spectratyping demonstrated evidence for selective clonal T cell accumulation in less than half of the lesional samples showing BV expansion. These results indicate that selective amplification of TCRBV species occurs in early psoriasis vulgaris but is not essential to the pathogenic process and may be more important in the maintenance or expansion of chronic lesions.
多个研究小组通过测定T细胞受体(TCR)β链可变(V)区的使用情况,对T细胞在寻常型银屑病和点滴状银屑病发病机制中的作用进行了研究,结果各异。由于在寻常型银屑病早期,尚无关于TCR表达的数据,而在这一阶段特定的细胞免疫事件可能最为显著,因此我们分析了10例患者的早期皮损(病程小于3周),结果具有高度可重复性。我们开发了一种高度可控的锚定聚合酶链反应(PCR)方法,其中所有TCRβ链种类均使用同一对引物进行扩增,产物通过与BV家族特异性寡核苷酸探针的斑点杂交进行定量分析。在大多数皮损活检样本中均观察到某些TCR BV基因的过表达,但在扩增的BV家族占皮损总BV超过10%的样本中(占分析样本的一半),BV2和BV6占主导地位。这些BV种类在患者之间过表达的一致性远低于先前对已形成的慢性斑块状银屑病皮损中TCRBV使用情况的研究。互补决定区3(CDR3)大小谱型分析表明,在不到一半显示BV扩增的皮损样本中存在选择性克隆性T细胞聚集。这些结果表明,TCRBV种类的选择性扩增发生在寻常型银屑病早期,但对致病过程并非必不可少,可能在慢性皮损的维持或扩展中更为重要。