Increased frequency of follicular helper T cells in mice viral myocarditis is relevant with anti-ANT antoantibody.
Increased frequency of follicular helper T cells in mice viral myocarditis is relevant with anti-ANT antoantibody.
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小鼠病毒性心肌炎滤泡辅助性 T 细胞频率增加与抗 ANT 抗体相关
DOI：
10.1186/s12985-015-0257-9
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发表时间：
2015-02-11
期刊：
影响因子：
4.8
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Yang F;Mo WH;Tan BP;Wei XM;Wang H
近年来，一种新的CD 4 +T辅助细胞亚群--滤泡辅助性T细胞（Follicular helper T cells，Tfh）被报道参与了某些自身免疫性疾病的发生发展，它在淋巴结构的B细胞活化和分化中起着关键作用。但Tfh细胞是否参与VMC的发病机制尚不清楚。用CVB 3腹腔感染雄性BALB/c小鼠建立VMC模型。分别于注射后0、1、2、3、4、6周，用流式细胞仪检测脾脏Tfh细胞的比例，用酶联免疫吸附试验检测IL-21和抗腺嘌呤核苷酸转运蛋白（ANT）自身抗体的产生。为了进一步研究Tfh细胞的作用，用抗IL-21中和抗体处理VMC小鼠。观察心脏组织病理学改变，并检测抗IL-21干预后Tfh细胞的出现率和抗ANT自身抗体的表达。采用斯皮尔曼分析法（Spearman）评价Tfh细胞频率与IL-21水平与抗ANT自身抗体的关系。VMC小鼠Tfh细胞百分比在1 ~ 6周显著升高，血清IL-21和ANT抗体水平也显著升高。用IL-21抗体中和IL-21可减轻IL-21抗体干预后的心肌炎症反应，降低Tfh细胞和ANT自身抗体，与对照组比较差异有显著性（P < 0.05）。Tfh细胞频率和IL-21水平与抗ANT抗体水平呈正相关（R = 0.758，P < 0.05; R = 0.88，P < 0.01）。提示Tfh细胞和IL-21可能参与了VMC的发病过程，并在抗ANT自身抗体的产生中起重要作用。靶向Tfh细胞和IL-21可能成为治疗CVB 3诱导的VMC的新靶点。
Recently, a new subset of CD4+T helper cell termed Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, has been reported to participate in some certain autoimmune diseases. But whether Tfh cells are involved in the pathogenesis of VMC remains unclear. Male BALB/c mice were intraperitoneally (i.p) infected with CVB3 to establish VMC models. Control mice were treated with phosphate-buffered saline i.p. On 0, 1, 2, 3, 4, 6 weeks post injection, frequencies of splenic Tfh cells were determined by flow cytometric analysis, productions of IL-21 and anti-adenine nucleotide translocator(ANT) autoantibody were detected by enzyme-linked immunosorbent assay. To further investigate the effects of Tfh cells, VMC mice were treated with Anti-IL-21 neutralizing antibody. Heart pathology was examined histologically, the frequencies of Tfh cells and the expressions of anti-ANT autoantibody were investigated after anti-IL-21 intervention. Spearman analysis was used to evaluate the relationship between the frequencies of Tfh cells and IL-21 levels with anti-ANT autoantibody. The percentage of Tfh cells significantly increased in VMC mice from 1 W to 6 W, the serum level of IL-21 and ANT autoantibody were also significantly increased in VMC mice. Neutralization of IL-21 with anti-IL-21 can ameliorate the myocardium inflammation, decrease Tfh cells and ANT autoantibody after IL-21 antibody intervention compared with those of the control (P < 0.05). Both of the frequencies of Tfh cells and IL-21 levels were positively correlated with anti-ANT antibody levels (R = 0.758, P < 0.05; R = 0.88, P < 0.01, respectively). Those results suggest that Tfh cells and IL-21 might involve in the pathogenesis of VMC and play an important role in anti-ANT autoantibody production. Targeting the Tfh cell and IL-21 may be a new therapeutic target for the treatment of CVB3-induced VMC.
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