Abdulahad Wayel H, Stegeman Coen A, Limburg Pieter C, Kallenberg Cees G M
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Ann N Y Acad Sci. 2007 Jun;1107:22-31. doi: 10.1196/annals.1381.003.
Although the cause of ANCA-associated vasculitis (AAV) remains undetermined, the presence of lymphocytic infiltrates in inflammatory lesions of patients suggests that vascular damage is immune mediated. Studies over the past decade have implicated a role for T cells in the pathogenesis of AAV as altered T cell phenotype has been observed in this disorder. The distribution of T cell subpopulations has been analyzed most intensely in Wegener's granulomatosis (WG), where an expanded population of circulating CD4(+) effector memory T cells (CD4(+)T(EM)) was demonstrated. CD4(+)T(EM) cells play a major role in the pathogenesis of several autoimmune diseases. Specific suppression of CD4(+)T(EM) cells inhibits delayed-type hypersensitivity (DTH) and has therapeutic potential in autoimmune disease. Thus, CD4(+)T(EM) cells may act as inducers of tissue injury and participate in the development of AAV. Therapies that target CD4(+)T(EM), without impairing the activity of other lymphocyte subsets, may hold therapeutic promise for AAV.
尽管抗中性粒细胞胞浆抗体相关性血管炎(AAV)的病因尚未明确,但患者炎症病变中淋巴细胞浸润的存在提示血管损伤是免疫介导的。过去十年的研究表明,T细胞在AAV发病机制中起作用,因为在这种疾病中观察到了T细胞表型的改变。T细胞亚群的分布在韦格纳肉芽肿(WG)中得到了最深入的分析,在那里发现循环中的CD4(+)效应记忆T细胞(CD4(+)T(EM))群体有所扩大。CD4(+)T(EM)细胞在几种自身免疫性疾病的发病机制中起主要作用。特异性抑制CD4(+)T(EM)细胞可抑制迟发型超敏反应(DTH),并在自身免疫性疾病中具有治疗潜力。因此,CD4(+)T(EM)细胞可能作为组织损伤的诱导剂,并参与AAV的发展。靶向CD4(+)T(EM)而不损害其他淋巴细胞亚群活性的疗法可能对AAV具有治疗前景。