Yilmaz Atilla, Rowley Anne, Schulte Danica J, Doherty Terence M, Schröder Nicolas W J, Fishbein Michael C, Kalelkar Mitra, Cicha Iwona, Schubert Katja, Daniel Werner G, Garlichs Christoph D, Arditi Moshe
Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany.
Exp Mol Pathol. 2007 Aug;83(1):93-103. doi: 10.1016/j.yexmp.2007.01.007. Epub 2007 Feb 1.
Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD.
越来越多的证据表明，树突状细胞（DCs）和T细胞参与了多种血管炎性疾病，如巨细胞动脉炎、高安动脉炎和动脉粥样硬化，这使我们推测它们可能也参与了川崎病（KD）冠状动脉炎的发病机制。我们获取了4例KD患者和6例对照患者的冠状动脉标本。进行了免疫组织化学和计算机辅助组织形态计量分析，以检测所有髓样DCs（S-100(+)、fascin(+)）、所有浆细胞样DCs（CD123(+)）以及特定的DC亚群（成熟髓样DCs [CD83(+)]、髓样[BDCA-1(+)]和浆细胞样DC前体[BDCA-2(+)]）、T细胞（CD3(+)）以及所有抗原呈递细胞（HLA-DR(+)）。使用双重免疫染色评估DCs与T细胞的共定位。与对照组相比，KD患者冠状动脉病变中处于前体、未成熟或成熟阶段的髓样DCs明显更多。髓样DC前体在内膜和外膜中分布均匀。成熟髓样DCs在外膜中特别丰富。成熟DCs与HLA-DR表达之间存在显著相关性。双重免疫染色显示，在外膜中层和外膜中，髓样DCs与T细胞频繁接触。浆细胞样DC前体在外膜中很少见。总之，KD患者的冠状动脉病变中含有数量增加的成熟髓样DCs，其HLA-DR表达高，免疫组织化学检测显示T细胞接触频繁。这表明成熟的动脉髓样DCs可能在原位激活T细胞，可能是KD冠状动脉炎发病机制中的一个重要因素。
