Akdis M, Simon H U, Weigl L, Kreyden O, Blaser K, Akdis C A
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
J Immunol. 1999 Jul 1;163(1):466-75.
In allergic inflammations of the skin, activation of CD4+ T cells was demonstrated to play an important role; however, a minor role for CD8+ T cells is implied. In the present study, we compared cutaneous lymphocyte-associated Ag (CLA)-expressing CD4+ and CD8+ subsets, which were isolated from peripheral blood and lesional skin biopsies in atopic dermatitis (AD) patients. We demonstrated that CD8+CLA+ T cells proliferate in response to superantigen and are as potent as CD4+CLA+ T cells in IgE induction and support of eosinophil survival. In atopic skin inflammation, the existence of high numbers of CD4+ and CD8+ T cells was demonstrated by immunohistochemistry and by culturing T cells from skin biopsies. In peripheral blood, both CD4+ and CD8+ subsets of CLA+CD45RO+ T cells were in an activated state in AD. The in vivo-activated CLA+ T cells of both subsets spontaneously released an IL-5- and IL-13-dominated Th2 type cytokine pattern. This was confirmed by intracytoplasmic cytokine staining immediately after isolation of the cells from peripheral blood. In consequence, both CD4+ and CD8+, CLA+ memory/effector T cells induced IgE production by B cells mainly by IL-13, and enhanced eosinophil survival in vitro by delaying eosinophil apoptosis, mainly by IL-5. These results indicate that in addition to the CD4+ subset, the CD8+CLA+ memory/effector T cells are capable of responding to superantigenic stimulation and play an important role in the pathogenesis of AD.
在皮肤过敏性炎症中,已证明CD4+ T细胞的激活起重要作用;然而,也暗示了CD8+ T细胞起次要作用。在本研究中,我们比较了从特应性皮炎(AD)患者外周血和皮损活检组织中分离出的表达皮肤淋巴细胞相关抗原(CLA)的CD4+和CD8+亚群。我们证明CD8+CLA+ T细胞可对超抗原产生增殖反应,并且在诱导IgE和支持嗜酸性粒细胞存活方面与CD4+CLA+ T细胞一样有效。在特应性皮肤炎症中,通过免疫组织化学以及培养皮肤活检组织中的T细胞,证实了大量CD4+和CD8+ T细胞的存在。在AD患者的外周血中,CLA+CD45RO+ T细胞的CD4+和CD8+亚群均处于激活状态。这两个亚群在体内被激活的CLA+ T细胞均自发释放以IL-5和IL-13为主的Th2型细胞因子模式。从外周血中分离细胞后立即进行的胞内细胞因子染色证实了这一点。因此,CD4+和CD8+、CLA+记忆/效应T细胞均主要通过IL-13诱导B细胞产生IgE,并主要通过IL-5延迟嗜酸性粒细胞凋亡,从而在体外增强嗜酸性粒细胞的存活。这些结果表明,除了CD4+亚群外,CD8+CLA+记忆/效应T细胞也能够对超抗原刺激作出反应,并在AD的发病机制中起重要作用。