Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune mediated diseases triggered by group A streptococcal (GAS) infections. Molecular mimicry between GAS M-proteins and host tissue proteins has been proposed as the mechanism that initiates autoreactive immune responses in ARF/RHD. However, the individual role of antibodies and T-cells specific for GAS M-proteins in the pathogenesis of autoimmune carditis remains under-explored. The current study investigated the role of antibodies and T-cells in the development of carditis in the Lewis rat autoimmune valvultis (RAV) model by transferring serum and/or splenic T-cells from rats previously injected with GAS recombinant M5 protein. Here we report that serum antibodies alone and serum plus in vitro expanded rM5-specific T-cells from hyperimmune rats were capable of transferring carditis to naïve syngeneic animals. Moreover, the rats that received combined serum and T-cells developed more severe carditis. Recipient rats developed mitral valvulitis and myocarditis and showed prolongation of P-R intervals in electrocardiography. GAS M5 protein-specific IgG reactivity and T-cell recall response were also demonstrated in recipient rats indicating long-term persistence of antibodies and T-cells following transfer. The results suggest that both anti-GAS M5 antibodies and T-cells have differential propensity to induce autoimmune mediated carditis in syngeneic rats following transfer. The results highlight that antibodies and effector T-cells generated by GAS M protein injection can also independently home into cardiac tissue to cross-react with tissue proteins causing autoimmune mediated immunopathology.

中文翻译：

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A组链球菌M蛋白特异性抗体和T细胞驱动大鼠自身免疫性瓣膜炎模型中观察到的病理。

急性风湿热（ARF）和风湿性心脏病（RHD）是由A组链球菌（GAS）感染引发的自身免疫介导的疾病。已经提出GAS M蛋白和宿主组织蛋白之间的分子模拟是引发ARF / RHD中自身反应性免疫反应的机制。然而，针对GAS M蛋白的抗体和T细胞在自身免疫性心脏病的发病机制中的个别作用仍未得到充分研究。当前的研究通过转移先前注射过GAS重组M5蛋白的大鼠的血清和/或脾脏T细胞，研究了Lewis和大鼠自身免疫性Valvultis（RAV）模型中抗体和T细胞在心脏病发展中的作用。在这里，我们报道，来自超免疫大鼠的血清抗体和血清加上体外扩增的rM5特异性T细胞能够将心脏炎转移至幼稚的同系动物。此外，接受血清和T细胞联合治疗的大鼠发展为更严重的心脏病。收件人大鼠发展为二尖瓣膜炎和心肌炎，并在心电图中显示PR间隔延长。在受体大鼠中还证实了GAS M5蛋白特异性IgG反应性和T细胞召回反应，表明转移后抗体和T细胞具有长期持久性。结果表明，抗GAS M5抗体和T细胞在转移后在同系大鼠中诱导自身免疫介导的心脏炎的倾向不同。