Chang J C, Smith L R, Froning K J, Schwabe B J, Laxer J A, Caralli L L, Kurland H H, Karasek M A, Wilkinson D I, Carlo D J
Immune Response Corporation, Carlsbad, CA 92008.
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9282-6. doi: 10.1073/pnas.91.20.9282.
Psoriasis is an inflammatory skin disorder characterized by epidermal keratinocyte hyperproliferation in association with a cellular infiltrate. There is evidence that activated T cells play a role in psoriatic plaque formation. We examined the T-cell receptor beta-chain variable gene segment (V beta) use of epidermal T cells in shave biopsies of psoriatic lesions. Our results show increased expression of V beta 3 and/or V beta 13.1 messages in the CD8+, but not CD4+, T cells in the lesions of a majority of patients studied. Sequence analysis of complementarity-determining region 3 (CDR3) of these two V beta genes from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy from the same or different lesions, performed 3.5-8 months later in four patients, again revealed increased V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology between patients. In two patients in which V beta 3 and/or V beta 13.1 was not increased, an increase in V beta 17 gene use and clonality was found. The clonality of V beta sequence data indicates these cells are recruited and expanded in situ. The persistence of V beta 3-and/or V beta 13.1-bearing CD8+ T cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells.
银屑病是一种炎症性皮肤病,其特征为表皮角质形成细胞过度增殖并伴有细胞浸润。有证据表明活化的T细胞在银屑病斑块形成中起作用。我们检测了银屑病皮损刮除活检中表皮T细胞的T细胞受体β链可变基因片段(Vβ)的使用情况。我们的结果显示,在大多数研究患者的皮损中,Vβ3和/或Vβ13.1信息在CD8⁺ T细胞中表达增加,而在CD4⁺ T细胞中未增加。对来自皮肤的这两个Vβ基因的互补决定区3(CDR3)进行序列分析,显示为单克隆性或明显的寡克隆性。在4例患者中,于3.5 - 8个月后从相同或不同皮损处再次进行活检,再次发现Vβ3和/或Vβ13.1表达增加及克隆性。此外,在这4例患者中的3例中,两次活检均发现相同的Vβ CDR3重排,尽管患者之间不存在Vβ CDR3同源性。在2例Vβ3和/或Vβ13.1未增加的患者中,发现Vβ17基因使用增加及克隆性。Vβ序列数据的克隆性表明这些细胞是在原位募集和扩增的。在未消退皮损中持续存在携带Vβ3和/或Vβ13.1的CD8⁺ T细胞,提示它们作为效应细胞而非调节细胞发挥作用。