HUMAN HEART-INFILTRATING T-CELL CLONES FROM RHEUMATIC HEART-DISEASE PATIENTS RECOGNIZE BOTH STREPTOCOCCAL AND CARDIAC PROTEINS
HUMAN HEART-INFILTRATING T-CELL CLONES FROM RHEUMATIC HEART-DISEASE PATIENTS RECOGNIZE BOTH STREPTOCOCCAL AND CARDIAC PROTEINS
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DOI：
10.1161/01.cir.92.3.415
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发表时间：
1995-08-01
期刊：
影响因子：
37.8
通讯作者：
KALIL, J
中科院分区：
文献类型：
--
作者：
GUILHERME, L;CUNHANETO, E;KALIL, J
背景：在发展中国家，β-溶血性链球菌感染仍然导致成千上万的风湿性心脏病病例，需要外科瓣膜矫正。自身和链球菌成分之间的抗原模拟被认为是导致遗传易感性个体自身免疫的触发因素。虽然心脏链球菌-M蛋白交叉反应抗体已被证明，心脏组织损伤似乎是T淋巴细胞依赖性的。我们研究了浸润性T淋巴细胞在风湿性心脏病病变的目的是了解在该网站的lesions.Methods和结果的细胞免疫反应的作用，我们获得了107个T细胞克隆手术片段的心脏组织从四个风湿性心脏病患者。我们测试了它们识别链球菌M蛋白衍生的合成肽和心脏蛋白的能力。我们从所有四名患者中发现了八个浸润性T细胞克隆，它们同时识别链球菌M和心脏蛋白。在测试的M蛋白序列中，只有对应于区域1至25、81至103和163至177的合成肽与心脏蛋白组分同时识别。有趣的是，已知区域81至103和163至177在抗体水平上具有心脏交叉反应性表位。结论风湿性心脏病患者存在心脏-M蛋白交叉反应性T细胞克隆，提示其与风湿性心脏病的发病有直接关系。链球菌M蛋白的保护性和致病性表位的剖析是开发安全的抗链球菌合成疫苗的重要一步。
Background beta-Hemolytic streptococcal infection in developing countries still causes thousands of cases of rheumatic heart disease, demanding surgical valve correction. Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility. Although heart streptococcal-M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte-dependent. We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions.Methods and Results We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients. We tested their capacity to recognize streptococcal M protein-derived synthetic peptides and heart proteins. We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins. Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions. Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level. Five of these clones are CD4(+), and one is CD8(+).Conclusions The presence of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease. The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.