Antibody-mediated infection and cytotoxic T cells in cosackievirus B3 myocarditis

研究了Fc受体（FcR）介导的柯萨奇病毒B3 （CB3）在体外和体内的感染。当P388D1细胞（小鼠巨噬细胞样细胞系）被CB3感染时，暴露于不同浓度的抗CB3兔免疫球蛋白G （Igg）或其Fab片段，在亚中和浓度的Igg下观察到CB3的感染增强，而Fab片段则没有。此外，我们在体内证实了这种感染途径的存在。预接种心肌CB3后具有不同免疫水平的C_3H/He小鼠再接种心肌CB3。与免疫水平高或无免疫的小鼠相比，免疫水平低的小鼠心肌炎的严重程度和心肌Cb3滴度明显增强。因此，免疫力不足可能并不总是提供良性或保护性影响。这种免疫反应促进了再感染，可能诱发慢性活动性心肌炎。此外，肠病毒启动记忆T细胞在体内对任何与初次攻击病毒具有相同表位的嗜心性肠病毒的二次接种反应相似。因此，在第二次肠病毒感染期间，T细胞介导的对肠道病毒中保守抗原表位的免疫应答参与了心肌炎症性疾病的恶化。继发性感染模型可能更准确地反映人类人群中病毒诱导的心肌炎，因为大多数成年人在诱导疾病之前已经暴露于几种肠道病毒。

Fc receptor (FcR)-mediated coxsackievirus B3 (CB3) infection in vitro and in vivo was investigated. When P388D1 cells (a murine macrophage-like cell line) were infected with CB3 exposed previously to various concentrations of anti-CB3 rabbit immunoglobulin G (Igg) or its Fab fragment, enhanced infection of CB3 was observed at a subneutralizing concentration of IgG, but not of Fab fragment. In addition, we confirmed the existence of this infectious pathway in vivo. C_3H/He mice with various levels of immunity by preinoculation of amyocarditic CB3 were reinoculated with myocarditic CB3. The severity of myocarditis and myocardial Cb3 titers were markedly enhanced in the mice with a low level of immunity compared to those with high or no immunity. Therefore, the insufficient immunity may not always provide a benign or protective influence. This immunological response facilitates the reinfection possibly inducing chronic active myocarditis.In addition, enterovirus-primed memory T cells would react similarly in vivo to a secondary inoculation with any cardiotropic enterovirus that shares an epitope(s) with the primary challenge virus. Thus, T cell-mediated immune responses to conserved antigenic epitopes among the enteroviruses was involved in the exacerbation of myocardial inflammatory disease during a second enterovirus infection. The secondary infection model may more accurately mirror virus-induced myocarditis in the human population because the majority of adults have exposed t several enteroviruses before induction of disease.