Expanding regulatory T cells alleviates chikungunya virus-induced pathology in mice.
Expanding regulatory T cells alleviates chikungunya virus-induced pathology in mice.
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DOI：
10.1128/jvi.00998-15
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发表时间：
2015-08-01
影响因子：
5.4
通讯作者：
Ng LF
中科院分区：
文献类型：
--
作者：
Lee WW;Teo TH;Her Z;Lum FM;Kam YW;Haase D;Rénia L;Rötzschke O;Ng LF
基孔肯雅病毒（Chikungunya virus，CHIKV）感染是一种重新出现的大流行性人虫媒病毒病。先前显示CD 4 + T细胞在小鼠中CHIKV感染过程中有助于关节炎症。JES 6 -1抗IL-2抗体通过与IL-2形成复合物来选择性扩增小鼠调节性T细胞（Tcells）。在这项研究中，我们表明IL-2 JES 6 -1介导的TcB扩增改善了CHIKV诱导的关节病理学。它通过抑制CD 4 + T细胞的浸润来实现，这是由于CHIKV特异性CD 4+效应T细胞中无反应性的诱导。这些发现表明，激活THBE也可能成为控制CHIKV介导的疾病的替代方法。 基孔肯雅病毒（CHIKV）已经重新成为一种具有全球意义的病原体。感染CHIKV的患者患有严重影响其日常功能的失能性关节疼痛。尽管作出了最大努力，但治疗仍然不足。虽然已经报道了CHIKV感染中的T细胞介导的免疫病理学，但尚未探索调节性T细胞（Tcells）的作用。JES 6 -1抗白细胞介素2（IL-2）抗体已被证明通过与IL-2形成复合物选择性扩增小鼠T淋巴细胞。我们在这里揭示，IL-2 JES 6 -1介导的Teff扩增通过中和病毒特异性CD 4+效应T（Teff）细胞来改善小鼠中CHIKV诱导的关节病理学。我们表明，这种治疗通过诱导CHIKV特异性CD 4 + Teff细胞的无反应性来消除致病性CD 4 + T细胞的浸润。这是证明THBE在CHIKV发病机制中的作用的第一个证据，并且其扩增可以控制病毒介导的免疫病理学。
Chikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+ T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+ T cells due to the induction of anergy in CHIKV-specific CD4+ effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease. IMPORTANCE Chikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+ effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+ T cells through induction of anergy in CHIKV-specific CD4+ Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.