School of Veterinary Medicine and Biomedical Sciences and Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Curr Opin Rheumatol. 2013 Jul;25(4):502-8. doi: 10.1097/BOR.0b013e3283620036.
To review how autoimmunity is induced in viral myocarditis.
Clinical and experimental myocarditis follows microbial infections, but autoimmunity to cardiac antigens leads to heart failure since infected myocytes are sparse and virus clearance is rapid. In mice, CD4+ T cells specific for cardiac alpha myosin heavy chain (αMYHC) cause myocarditis and mice tolerized to αMYHC are protected from virus challenge proving pathogenesis depends upon autoimmunity. Most importantly, multiple microbes share the same mimicking epitope with αMYHC. Serial infections with very different microbes could result in memory responses to the shared epitope leading to aggressive and severe heart failure. A similar phenomenon may explain autoimmune diseases with suspected infectious causes, where specific pathogens have not been identified. Production of the relevant cardiac epitope for antigen presentation requires more than myosin release from dead myocytes. Otherwise, myocarditis would commonly follow myocardial infarcts. The inherent nature of the innate immune response associated with viral infections in the heart is crucial to cardiac epitope expression.
Antigenic mimicry between microbes and cardiac proteins causes autoimmunity in myocarditis. Characteristics of innate immunity associated with cardiac infection determine relevant epitope expression (cryptic epitopes).
病毒心肌炎中自身免疫是如何诱导的。
临床和实验性心肌炎跟随微生物感染，但心脏抗原的自身免疫导致心力衰竭，因为感染的心肌细胞稀少且病毒清除迅速。在小鼠中，针对心脏α肌球蛋白重链（αMYHC）的 CD4+T 细胞可引起心肌炎，而对αMYHC 耐受的小鼠则可免受病毒挑战的保护，这证明发病机制取决于自身免疫。最重要的是，许多微生物与αMYHC 具有相同的模拟表位。与非常不同的微生物的连续感染可能导致对共同表位的记忆反应，从而导致侵袭性和严重的心力衰竭。类似的现象可能解释了具有可疑感染原因的自身免疫性疾病，其中尚未确定特定的病原体。用于抗原呈递的相关心脏表位的产生需要的不仅仅是从死心肌细胞中释放肌球蛋白。否则，心肌炎通常会跟随心肌梗死。与心脏病毒感染相关的固有先天免疫反应的固有性质对心脏表位表达至关重要。
微生物和心脏蛋白之间的抗原模拟导致心肌炎中的自身免疫。与心脏感染相关的先天免疫的特征决定了相关表位的表达（隐匿表位）。
