Low levels of SIV infection in sooty mangabey central memory CD⁴⁺ T cells are associated with limited CCR5 expression.

Low levels of SIV infection in sooty mangabey central memory CD⁴⁺ T cells are associated with limited CCR5 expression.
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烟熏芒果中央记忆CD⁴⁺T细胞中SIV感染水平的低水平与CCR5表达有限有关。

DOI:
10.1038/nm.2395
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发表时间:
2011-06-26
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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自然感染SIV的白眉猴(SM)不会发展为艾滋病,尽管病毒复制水平很高。我们先前表明,与人类和猕猴相比,SM中CD4+CCR5+ T细胞的比例较低。在这里,我们发现,在体外刺激后,SM CD4+ T细胞未能上调CCR5,并且这种现象在CD4+中央记忆T细胞(TCM)中更为明显。在(i)急性SIV感染期间和(ii)抗体介导的CD4 + T细胞耗竭之后,体内SM中的CD4+ T细胞活化与CCR5表达类似地解偶联。值得注意的是,与RM的CD4+ TCM相比,表达低水平CCR5的SM的CD4+ TCM在体内和体外均表现出对SIV感染的易感性降低。这些数据表明,SM CD4+ T细胞上的低CCR5表达有利于保持CD4+ T细胞的稳态,并通过保护CD4+ TCM免受直接病毒感染而促进无AIDS状态。
Naturally SIV-infected sooty mangabeys (SMs) do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4+CCR5+ T-cells is lower in SMs compared to humans and macaques. Here we found that, after in vitro stimulation, SM CD4+ T-cells fail to up-regulate CCR5, and that this phenomenon is more pronounced in CD4+ central-memory T-cells (TCM). CD4+ T-cell activation was similarly uncoupled from CCR5 expression in SMs in vivo during (i) acute SIV infection and (ii) following antibody-mediated CD4+ T-cell depletion. Remarkably, CD4+ TCM of SMs that express low levels of CCR5 demonstrated reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4+ TCM of RMs. These data suggest that low CCR5 expression on SM CD4+ T-cells favors the preservation of CD4+ T-cell homeostasis and promotes an AIDS-free status by protecting CD4+ TCM from direct virus infection.
记忆中的CD4下调CD4+ T细胞体内使非洲绿色猴子具有对进行性Sivagm感染的抗性。
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