Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis
Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis
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DOI：
10.1006/clin.1996.0078
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Weyand, CM
中科院分区：
文献类型：
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作者：
MartinezTaboada, VM;Goronzy, JJ;Weyand, CM
巨细胞动脉炎（GCA）是一种血管炎性实体，专门影响50岁以上的人。风湿性多肌痛（PMR）是一种密切相关的疾病，缺乏临床显著的血管炎病变，但与GCA的年龄依赖性和HLA相关性相同。为了研究T细胞受体库中与年龄相关的变化是否是这两种疾病的危险因素，我们分析了外周血CD 8（+）T细胞的多样性。未经治疗的PMR/GCA患者携带多个克隆扩增的CD 8群体。克隆扩增的频率与年龄匹配的健康对照组没有差异。对CD 8（+）克隆型的分子分析显示，与正常对照组相比，具有不同J β基因片段使用的患者的库受限。J β 2.7（+）CD 8（+）克隆型仅见于患者。选择性CD 8细胞扩增的进一步证据来自于发现尽管V β元件多样性，但同一患者中的多个克隆型转录相同的J β片段。尽管成功控制了疾病活动，但CD 8库中的寡克隆性持续存在，表明CD 8（+）克隆型不是炎症的附带现象。我们认为，选择的CD 8（+）细胞在GCA和PMR的发病机制中具有重要的功能，通过J β特异性机制。CD 8 T细胞受体库的组成中与这种克隆型的出现相关的变化可能使个体易患PMR/GCA。(C)出版社：Academic Press，Inc.
Giant cell arteritis (GCA) is a vasculitic entity which exclusively affects individuals older than 50 years of age. Polymyalgia rheumatica (PMR) is a closely related condition which lacks clinically significant vasculitic lesions but shares with GCA the age dependence and the HLA association. To examine whether age-related changes in the T cell receptor repertoire represent a risk factor in these two diseases, we have analyzed the diversity of peripheral blood CD8(+) T cells. Untreated PMR/GCA patients carried multiple clonally expanded CD8 populations. The frequency of clonal expansion was not different from age-matched healthy controls. Molecular analysis of the CD8(+) clonotypes showed a restricted repertoire in the patients with a distinct J beta gene segment usage compared to normal controls. J beta 2.7(+) CD8(+) clonotypes were exclusively found in patients. Further evidence for selective CD8 cell expansion came hom the finding that multiple clonotypes in the same patient transcribed identical J beta segments despite diversity of the V beta element. Oligoclonality in the CD8 repertoire persisted despite successful control of the disease activity, suggesting that the CD8(+) clonotypes are not an epiphenomenon of the inflammation. We propose that selected CD8(+) cells are of functional importance in the pathogenesis of GCA and PMR through a J beta-specific mechanism. Age-related changes in the composition of the CD8 T cell receptor repertoire with the emergence of such clonotypes may predispose individuals to develop PMR/GCA. (C) 1996 Academic Press, Inc.