Interleukin-10 determines viral clearance or persistence in vivo
Interleukin-10 determines viral clearance or persistence in vivo
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DOI：
10.1038/nm1492
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发表时间：
2006-11-01
期刊：
影响因子：
82.9
通讯作者：
Oldstone, Michael B. A.
中科院分区：
文献类型：
--
作者：
Brooks, David G.;Trifilo, Matthew J.;Oldstone, Michael B. A.
持续的病毒感染是一个主要的健康问题。抑制持续感染清除的一个障碍是抗病毒T细胞的功能失活。尽管这种免疫抑制在感染后迅速发生，但诱导t细胞活性丧失和促进病毒持久性的机制尚不清楚。在这里，我们证明了小鼠持续的病毒感染导致抗原呈递细胞显著上调白细胞介素(IL)-10，导致t细胞反应受损。遗传去除II10导致维持强大的效应t细胞反应，快速消除病毒和抗病毒记忆t细胞反应的发展。治疗性用药阻断IL-10受体的抗体可恢复t细胞功能并消除病毒感染。因此，我们确定了一个直接诱导免疫抑制导致病毒持续存在的单分子，并证明了一种中和IL-10的治疗可导致t细胞恢复和病毒持续存在的预防。
Persistent viral infections are a major health concern. One obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral T cells. Although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of T-cell activity and promote viral persistence are unknown. Herein we document that persistent viral infection in mice results in a significant upregulation of interleukin (IL)-10 by antigen-presenting cells, leading to impaired T-cell responses. Genetic removal of II10 resulted in the maintenance of robust effector T-cell responses, the rapid elimination of virus and the development of antiviral memory T-cell responses. Therapeutic administration of an antibody that blocks the IL-10 receptor restored T-cell function and eliminated viral infection. Thus, we identify a single molecule that directly induces immunosuppression leading to viral persistence and demonstrate that a therapy to neutralize IL-10 results in T-cell recovery and the prevention of viral persistence.