Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis.
Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis.
复制标题
DOI：
10.1084/jem.20030850
复制
发表时间：
2004-01-19
期刊：
影响因子：
--
通讯作者：
Weyand CM
中科院分区：
文献类型：
--
作者：
Ma-Krupa W;Jeon MS;Spoerl S;Tedder TF;Goronzy JJ;Weyand CM
巨细胞动脉炎（GCA）是一种肉芽肿性和闭塞性血管炎，可导致失明、中风和主动脉瘤。CD 4 + T细胞在受影响动脉的外膜中被选择性激活。在人GCA动脉-严重联合免疫缺陷（SCID）小鼠嵌合体中，CD 83+树突状细胞（DC）的耗竭消除了血管炎，表明DC是GCA中关键的抗原呈递细胞。健康的中等大小的动脉在外膜-中膜边界处具有DC的土著群体。过继性T细胞转移到颞动脉-SCID小鼠嵌合体中表明，健康动脉中的DC功能不成熟，但在注射脂多糖后获得了T细胞刺激能力。在风湿性多肌痛（PMR）患者中，GCA的亚临床变异，外膜DC成熟并产生趋化因子CCL 19和CCL 21，但缺乏血管炎浸润。将人类组织相容性白细胞抗原II类匹配的健康动脉、PMR动脉和GCA动脉共植入SCID小鼠。健康动脉中的未成熟DC不能刺激T细胞，但PMR动脉中的DC可以吸引、保留和激活源自GCA病变的T细胞。我们认为，在原位成熟的树突状细胞在血管外膜是一个早期事件的发病机制GCA。外膜DC的激活启动并维持动脉中的T细胞应答，并打破血管周围空间中的组织耐受。
Giant cell arteritis (GCA) is a granulomatous and occlusive vasculitis that causes blindness, stroke, and aortic aneurysm. CD4+ T cells are selectively activated in the adventitia of affected arteries. In human GCA artery–severe combined immunodeficiency (SCID) mouse chimeras, depletion of CD83+ dendritic cells (DCs) abrogated vasculitis, suggesting that DCs are critical antigen-presenting cells in GCA. Healthy medium-size arteries possessed an indigenous population of DCs at the adventitia–media border. Adoptive T cell transfer into temporal artery–SCID mouse chimeras demonstrated that DCs in healthy arteries were functionally immature, but gained T cell stimulatory capacity after injection of lipopolysaccharide. In patients with polymyalgia rheumatica (PMR), a subclinical variant of GCA, adventitial DCs were mature and produced the chemokines CCL19 and CCL21, but vasculitic infiltrates were lacking. Human histocompatibility leukocyte antigen class II–matched healthy arteries, PMR arteries, and GCA arteries were coimplanted into SCID mice. Immature DCs in healthy arteries failed to stimulate T cells, but DCs in PMR arteries could attract, retain, and activate T cells that originated from the GCA lesions. We propose that in situ maturation of DCs in the adventitia is an early event in the pathogenesis of GCA. Activation of adventitial DCs initiates and maintains T cell responses in the artery and breaks tissue tolerance in the perivascular space.