Ablation of CD8 and CD4 T cell responses by high viral loads
Ablation of CD8 and CD4 T cell responses by high viral loads
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DOI：
10.4049/jimmunol.170.1.477
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发表时间：
2003-01-01
影响因子：
4.4
通讯作者：
Zajac, AJ
中科院分区：
文献类型：
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作者：
Fuller, MJ;Zajac, AJ
为了评估持续病毒载量对抗病毒T细胞应答的影响，我们比较了清除急性淋巴细胞性脉络丛脑膜炎病毒感染的应答与被激发但无法解决慢性感染的应答。在急性感染期间，随着复制病毒被清除，CD8 T细胞应答被下调，并且形成了一群静息记忆细胞。在慢性感染的宿主中，无法控制感染与病毒特异性CD8 T细胞显著且持久的活化有关。然而，随着它们产生白细胞介素 - 2（IL - 2）、然后是肿瘤坏死因子 -α（TNF -α）以及最终干扰素 -γ（IFN -γ）的能力丧失，其效应活性逐渐减弱。慢性淋巴细胞性脉络丛脑膜炎病毒感染还与某些CD8 T细胞应答的差异性收缩有关，导致免疫优势改变。然而，这种免疫优势的改变并非由于慢性感染期间表达特定T细胞受体Vβ片段的T细胞的选择性扩增。高病毒载量不仅与CD8 T细胞应答的消除有关，还与病毒特异性CD4 T细胞产生IL - 2受损有关。综上所述，我们的数据表明，持续暴露于高病毒载量会导致病毒特异性T细胞应答的渐进性功能失活，这可能进一步促进病毒的持续存在。
To evaluate the impact of sustained viral loads on anti-viral T cell responses we compared responses that cleared acute lymphocytic choriomeningitis virus infection with those that were elicited but could not resolve chronic infection. During acute infection, as replicating virus was cleared, CD8 T cell responses were down-regulated, and a pool of resting memory cells developed. In chronically infected hosts, the failure to control the infection was associated with pronounced and prolonged activation of virus-specific CD8 T cells, Nevertheless, there was a progressive diminution of their effector activities as their capacity to produce first IL-2, then TNF-alpha, and finally IFN-gamma was lost. Chronic lymphocytic choriomeningitis virus infection was also associated with differential contraction of certain CD8 T cell responses, resulting in altered immunodominance. However, this altered immunodominance was not due to selective expansion of T cells expressing particular TCR Vbeta segments during chronic infection. High viral loads were not only associated with the ablation of CD8 T cell responses, but also with impaired production of IL-2 by virus-specific CD4 T cells. Taken together, our data show that sustained exposure to high viral loads results in the progressive functional inactivation of virus-specific T cell responses, which may further promote virus persistence.