Regulatory T cells control diabetes without compromising acute anti-viral defense.
Regulatory T cells control diabetes without compromising acute anti-viral defense.
复制标题
DOI：
10.1016/j.clim.2014.05.006
复制
发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
von Herrath M
中科院分区：
文献类型：
--
作者：
Jones CB;Pagni PP;Fousteri G;Sachithanantham S;Dave A;Rodriguez-Calvo T;Miller J;von Herrath M
虽然先前的报道已经证明了调节性T细胞疗法在预防糖尿病中的功效，但全身性免疫功能低下和Treg不稳定性仍然是关键的安全性问题。在这里，我们研究了诱导Treg（iTreg）细胞疗法对自身免疫性糖尿病小鼠模型中急性病毒感染期间抗病毒宿主防御和自身免疫T细胞应答的影响。尽管失去了FoxP 3的表达，iTclase的保护性转移维持了IL-10的表达，并在体内扩增和控制糖尿病。虽然观察到了对CD 4 T细胞应答的显著和持续的抑制，但iT细胞的连续转移既不影响初级抗病毒CD 8 T细胞应答，也不影响病毒清除。在急性病毒清除后，iT细胞转移早期抑制CD 4和CD 8 T细胞应答，导致糖尿病逆转。这些观察结果表明，iTclad抑制局部自身免疫过程，同时保留免疫活性宿主对抗急性病毒感染的能力。
While previous reports have demonstrated the efficacy of regulatory T cell therapy in the prevention of diabetes, systemic immunocompromise and Treg instability remain key safety concerns. Here we examined the influence of induced Treg (iTreg) cell therapy on anti-viral host defense and autoimmune T cell responses during acute viral infection in a murine model of autoimmune diabetes. Protective transfers of iTregs maintained IL-10 expression, and expanded in vivo and controlled diabetes, despite losing FoxP3 expression. Adoptive transfer of iTregs affected neither the primary anti-viral CD8 T cell response nor viral clearance, although a significant and sustained suppression of CD4 T cell responses was observed. Following acute viral clearance, iTregs transferred early suppressed both CD4 and CD8 T cell responses, which resulted in the reversion of diabetes. These observations indicate that iTregs suppress local autoimmune processes while preserving the immunocompetent host's ability to combat acute viral infection.