Suppressive CD8+ T cells arise in the absence of CD4 help and compromise control of persistent virus.
Suppressive CD8+ T cells arise in the absence of CD4 help and compromise control of persistent virus.
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DOI：
10.4049/jimmunol.1003812
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Usherwood EJ
中科院分区：
文献类型：
--
作者：
Molloy MJ;Zhang W;Usherwood EJ
迫切需要开发新的治疗方法来控制免疫功能低下患者的慢性病毒感染。与持续性γ-疱疹病毒感染（EBV，人疱疹病毒8）相关的疾病是AIDS患者和移植受者中的重要问题，并且这些病症的临床管理是困难的。在缺乏CD 4 + T细胞的小鼠中，可以使用鼠γ-疱疹病毒（MHV）-68对免疫监视失败后的γ-疱疹病毒复发进行建模。与其他慢性感染相比，未检测到病毒特异性CD 8 + T细胞应答的功能能力的明显缺陷。我们在这篇文章中表明，过继转移MHV-68特异性CD 8 + T细胞在降低病毒负荷方面无效。总之，这些表明T细胞外源性抑制因子的潜在存在。事实上，用MHV-68感染的CD 4耗尽小鼠表达增加水平的IL-10，IL-10是一种能够抑制APC和T细胞功能的细胞因子。CD 4-耗尽的小鼠发展出能够产生抑制病毒控制的IL-10的CD 8 + T细胞群。虽然表现出细胞表面标志物的活化指示，IL-10-生产细胞表达的程序性死亡-1水平增加，但没有富集在MHV-68特异性区室，也不是均匀的CD 44 hi。IL-10 R阻断Ab的治疗性施用增强了对复发病毒的控制。这些数据表明IL-10是恢复免疫抑制个体对慢性γ-疱疹病毒感染的免疫监视的有希望的靶点。
There is an urgent need to develop novel therapies for controlling chronic virus infections in immunocompromised patients. Disease associated with persistent γ-herpesvirus infection (EBV, human herpesvirus 8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Immune surveillance failure followed by γ-herpes-virus recrudescence can be modeled using murine γ-herpesvirus (MHV)-68 in mice lacking CD4+ T cells. In contrast with other chronic infections, no obvious defect in the functional capacity of the viral-specific CD8+ T cell response was detected. We show in this article that adoptive transfer of MHV-68–specific CD8+ T cells was ineffective at reducing the viral burden. Together, these indicate the potential presence of T cell extrinsic suppressive factors. Indeed, CD4-depleted mice infected with MHV-68 express increased levels of IL-10, a cytokine capable of suppressing the function of both APCs and T cells. CD4-depleted mice developed a population of CD8+ T cells capable of producing IL-10 that suppressed viral control. Although exhibiting cell surface markers indicative of activation, the IL-10–producing cells expressed increased levels of programmed death-1 but were not enriched in the MHV-68–specific compartment, nor were they uniformly CD44hi. Therapeutic administration of an IL-10R blocking Ab enhanced control of the recrudescent virus. These data implicate IL-10 as a promising target for the restoration of immune surveillance against chronic γ-herpesvirus infection in immunosuppressed individuals.
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影响因子：
15.3
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