Zhang Bao-Xiang, Lyu Jun-Cheng, Liu Hai-Bo, Feng Dian-Qin, Zhang Dian-Cai, Bi Xing-Jie, Duan Zhi-Wu, Ding Gang
Department of Dermatology, Yidu Central Hospital, Weifang Medical University, Weifang, P.R. China.
Department of Health Statistics, Public Health College of Weifang Medical University, Weifang, P.R. China.
Yonsei Med J. 2015 Jan;56(1):196-203. doi: 10.3349/ymj.2015.56.1.196.
Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8⁺T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8⁺CLA⁺T cells might be underlying mechanism in AD.
CD8⁺CLA⁺T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8⁺CLA⁺T cells were evaluated. The proliferative responses of CD8⁺CLA⁺T cells were assessed by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay.
Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8⁺CLA⁺T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8⁺CLA⁺T cells in AD. Meanwhile, the levels of TGF-β1 produced by Tregs were significantly lower in AD, and anti-TGF-β1 abolished such suppression.
The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8⁺CLA⁺T cells, mediated by TGF-β1, plays an important role in the pathogenesis of AD.
已知表达皮肤淋巴细胞相关抗原（CLA）的CD8⁺T细胞在特应性皮炎（AD）的发病机制中起重要作用。然而，自身耐受性丧失的潜在机制仍不清楚。调节性T细胞（Tregs）在免疫系统稳态的发展中起关键作用。因此，我们推测Tregs抑制自体CD8⁺CLA⁺T细胞的能力降低可能是AD的潜在机制。
从AD患者和对照志愿者的外周血中获取CD8⁺CLA⁺T细胞和Tregs。评估CD8⁺CLA⁺T细胞的频率。通过流式细胞术评估CD8⁺CLA⁺T细胞的增殖反应，并通过酶联免疫吸附测定法检测培养上清液中转化生长因子-β1（TGF-β1）和白细胞介素-10（IL-10）的水平。
我们的结果显示，AD患者外周血CD8⁺CLA⁺T细胞中穿孔素和颗粒酶-B的频率更高且表达增加，AD中Tregs对CD8⁺CLA⁺T细胞增殖的抑制能力更低。同时，AD中Tregs产生的TGF-β1水平显著降低，抗TGF-β1消除了这种抑制作用。
Tregs对由TGF-β1介导的过度活化的自体CD8⁺CLA⁺T细胞的抑制能力减弱在AD的发病机制中起重要作用。
