Guilherme L, Faé K C, Oshiro S E, Tanaka A C, Pomerantzeff P M A, Kalil J
Laboratório de Imunologia, Instituto do Coração (HC-FMUSP), School of Medicine, University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 44-9 andar., 05403-000 São Paulo, SP, Brazil.
Ann N Y Acad Sci. 2005 Jun;1051:132-40. doi: 10.1196/annals.1361.054.
The pathogenesis of rheumatic fever (RF) is related to autoimmune humoral and cellular responses against human tissues triggered by Streptococcus pyogenes. CD4(+) T cells are the ultimate effectors of chronic heart lesions in rheumatic heart disease (RHD). Heart-infiltrating CD4(+) T cell clones are able to recognize heart tissue and streptococcal antigens by molecular mimicry. The streptococcal M5(81-103) region, an immunodominant region, was recognized by both intralesional and peripheral T cell clones (62% and 38%, respectively). Peripheral T lymphocytes from Brazilian patients with severe RHD preferentially recognized the M5(81-96) peptide, in the context of HLA-DR7(+) and DR53(+) molecules. HLA-DR7 seems to be related to the development of multiple valvular lesions in RHD patients from different countries. In addition, the fact that peripheral and intralesional T cells recognized the M5(81-103) region points to this region as one of the streptococcal triggers of autoimmune reactions in RHD. T cell repertoire analysis from peripheral and intralesional T cell lines derived from RHD patients showed several oligoclonal expansions of BV families. Major expansions were found in the heart lesions, suggesting that such T cell populations preferentially migrate from the periphery to the heart. Some cross-reactive intralesional T cell clones displayed the same T cell receptor (TCR) BVBJ and CDR3 sequences, showing a degenerate pattern of antigen recognition. Heart tissue-infiltrating cells from myocardium and valvular tissue produced TNF-alpha, IFN-gamma, IL-10, and IL-4, whereas few cells from valvular tissue produced IL-4, showing that the lack of regulation in the valves could be responsible for the permanent and progressive valvular lesions.
风湿热（RF）的发病机制与化脓性链球菌引发的针对人体组织的自身免疫体液和细胞反应有关。CD4(+) T细胞是风湿性心脏病（RHD）慢性心脏病变的最终效应细胞。浸润心脏的CD4(+) T细胞克隆能够通过分子模拟识别心脏组织和链球菌抗原。链球菌M5(81 - 103)区域是一个免疫显性区域，病灶内和外周T细胞克隆均能识别该区域（分别为62%和38%）。来自巴西重症RHD患者的外周T淋巴细胞在HLA - DR7(+)和DR53(+)分子的背景下优先识别M5(81 - 96)肽。HLA - DR7似乎与来自不同国家的RHD患者多发瓣膜病变的发生有关。此外，外周和病灶内T细胞识别M5(81 - 103)区域这一事实表明该区域是RHD自身免疫反应的链球菌触发因素之一。对来自RHD患者的外周和病灶内T细胞系进行的T细胞库分析显示，BV家族有多个寡克隆扩增。在心脏病变中发现了主要的扩增，这表明此类T细胞群体优先从外周迁移至心脏。一些交叉反应性病灶内T细胞克隆显示出相同的T细胞受体（TCR）BVBJ和CDR3序列，呈现出抗原识别的简并模式。心肌和瓣膜组织的心脏组织浸润细胞产生肿瘤坏死因子-α、干扰素-γ、白细胞介素-10和白细胞介素-4，而瓣膜组织中很少有细胞产生白细胞介素-4，这表明瓣膜缺乏调节可能是导致永久性和进行性瓣膜病变的原因。
