Schulte Danica J, Yilmaz Atilla, Shimada Kenichi, Fishbein Michael C, Lowe Emily L, Chen Shuang, Wong Michelle, Doherty Terence M, Lehman Thomas, Crother Timothy R, Sorrentino Rosalinda, Arditi Moshe
Pediatric Infectious Diseases, Cedars-Sinai Medical Center, University of California, Los Angeles, CA 90048, USA.
J Immunol. 2009 Oct 15;183(8):5311-8. doi: 10.4049/jimmunol.0901395. Epub 2009 Sep 28.
Kawasaki disease (KD) is the most common cause of acquired cardiac disease and acute vasculitis in children in the developed world. Injection of a cell wall extract isolated from Lactobacillus casei (LCCWE) into mice causes a focal coronary arteritis that histopathologically mimics the coronary lesions observed in KD patients. In this study we used this model to investigate the participation of T cells, B cells, and dendritic cells (DC) in the development of coronary arteritis. RAG1(-/-), B cell(null), and wild-type (WT) mice were injected with a single dose of LCCWE (500 microg/mouse i.p.). None of the RAG1(-/-) mice developed coronary arteritis, whereas 70% of WT and 100% of B cell(null) mice developed coronary lesions, indicating that T cells were required for lesion formation. When splenocytes isolated from LCCWE-treated mice were restimulated with LCCWE, we observed significant IFN-gamma secretion in WT but not in RAG1(-/-) mice. Immunohistochemical staining showed F4/80(+) macrophages, activated MIDC-8(+) myeloid DCs (mDC), plasmacytoid DCs, and colocalization of CD3(+) T cells with mDCs in coronary artery lesions, suggesting an Ag-driven process. T cells but not B cells are required for LCCWE-induced coronary arteritis. Similar to human lesions, the coronary lesions contain macrophages, activated mDCs, and plaslmacytoid DCs all in close proximity to T cells, further strengthening the relevance of this mouse model to the immunopathology of coronary disease in KD. These studies are consistent with the interpretation that macrophages and DCs may collaborate with T cells in the pathological mechanisms of coronary arteritis.
川崎病（KD）是发达国家儿童获得性心脏病和急性血管炎的最常见病因。向小鼠注射从干酪乳杆菌分离的细胞壁提取物（LCCWE）会导致局灶性冠状动脉炎，其组织病理学特征与KD患者中观察到的冠状动脉病变相似。在本研究中，我们使用该模型来研究T细胞、B细胞和树突状细胞（DC）在冠状动脉炎发展过程中的作用。给RAG1（-/-）、B细胞缺陷型和野生型（WT）小鼠腹腔注射单剂量的LCCWE（500μg/小鼠）。没有一只RAG1（-/-）小鼠发生冠状动脉炎，而70%的WT小鼠和100%的B细胞缺陷型小鼠出现冠状动脉病变，这表明病变形成需要T细胞。当用LCCWE再次刺激从LCCWE处理的小鼠中分离的脾细胞时，我们观察到WT小鼠中有显著的IFN-γ分泌，而RAG1（-/-）小鼠中则没有。免疫组织化学染色显示在冠状动脉病变中有F4/80（+）巨噬细胞、活化的MIDC-8（+）髓样DC（mDC）、浆细胞样DC，以及CD3（+）T细胞与mDC的共定位，提示这是一个抗原驱动的过程。LCCWE诱导的冠状动脉炎需要T细胞而不是B细胞。与人类病变相似，冠状动脉病变中含有巨噬细胞、活化的mDC和浆细胞样DC，它们都与T细胞紧密相邻，这进一步加强了该小鼠模型与KD中冠状动脉疾病免疫病理学的相关性。这些研究与巨噬细胞和DC可能在冠状动脉炎的病理机制中与T细胞协同作用的解释一致。
