Akdis Mübeccel, Trautmann Axel, Klunker Sven, Daigle Isabelle, Kucuksezer Umut C, Deglmann Wolfgang, Disch Rainer, Blaser Kurt, Akdis Cezmi A
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland.
FASEB J. 2003 Jun;17(9):1026-35. doi: 10.1096/fj.02-1070com.
T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA+) CD45RO+ T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified CLA+ CD45RO+ T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as pro-caspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.
T细胞在特应性/过敏性炎症中构成大量细胞浸润，而失调的、以Th2为主的外周免疫反应似乎是一个重要的致病因素。在特应性皮炎中，具有皮肤特异性归巢特性的循环皮肤淋巴细胞相关抗原阳性（CLA+）CD45RO+ T细胞代表一个活化的记忆/效应T细胞亚群。它们高水平表达Fas和Fas配体，并经历活化诱导的细胞凋亡。特应性个体新鲜纯化的CLA+ CD45RO+ T细胞表现出体内触发凋亡的独特特征，如前半胱天冬酶降解和活性半胱天冬酶-8形成。特别是，活化的记忆/效应T细胞的Th1亚群选择性地经历活化诱导的细胞死亡，使特应性皮炎患者的免疫反应偏向于存活的Th2细胞。循环记忆/效应T细胞的凋亡仅限于特应性个体，而银屑病、内源性哮喘、接触性皮炎、内源性特应性皮炎、蜂毒过敏患者和健康对照等非特应性患者在体内未显示T细胞凋亡增强的证据。这些结果确定了特应性疾病外周Th2反应的一种新机制。
