Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points
Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points
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DOI：
10.1073/pnas.1015148108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Dittmer, Ulf
中科院分区：
文献类型：
--
作者：
Dietze, Kirsten K.;Zelinskyy, Gennadiy;Dittmer, Ulf
尽管HIV和丙型肝炎病毒等病毒的慢性感染与调节性T细胞（Treg）介导的病毒特异性CD8(+) T细胞活性抑制有关，但Treg和慢性病毒设定点之间没有因果关系。通过使用Tregs可被选择性切除的转基因小鼠，我们现在发现在慢性逆转录病毒感染期间Tregs的短暂耗竭允许耗尽的CD8(+) T细胞重新获得抗病毒功能，包括分泌细胞因子、产生细胞毒性分子和病毒特异性的细胞溶解活性。此外，短期Treg消融导致慢性病毒载量的长期减少。这些结果表明treg介导的免疫抑制可能是维持慢性病毒感染的一个重要因素，treg靶向免疫治疗可能是治疗慢性传染病的治疗策略的一个有价值的组成部分。
Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8(+) T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8(+) T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.