TCF-1 regulates HIV-specific CD8+ T cell expansion capacity
TCF-1 regulates HIV-specific CD8+ T cell expansion capacity
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DOI：
10.1172/jci.insight.136648
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发表时间：
2021-02-08
期刊：
影响因子：
8
通讯作者：
Hunt, Peter W.
中科院分区：
文献类型：
--
作者：
Rutishauser, Rachel L.;Deguit, Christian Deo T.;Hunt, Peter W.
尽管许多HIV治疗策略寻求扩大HIV特异性CD8(+)T细胞来控制病毒，但如果不防止细胞耗尽，所有这些策略都可能失败。干细胞样记忆特性(即增殖和产生次级效应细胞的能力)的丧失是衰竭的一个关键特征；然而，关于这些特性是如何在人类病毒特异性CD8(+)T细胞中调节的，人们知之甚少。我们发现，来自自然控制HIV/SIV感染的人和非人灵长类动物的病毒特异性CD8(+)T细胞比非控制者表达更多的转录因子TCF-1。HIV特异性CD8(+)T细胞TCF-1的表达与记忆标记物的表达和扩增能力相关，并随抗原刺激而下降。CRISPR-Cas9编辑人类原代T细胞中的TCF-1显示了在调节扩增能力方面的直接作用。总之，这些数据表明，TCF-1有助于调节HIV特异性CD8(+)T细胞二次扩增能力的干性记忆特性，并为在以T细胞为基础的HIV治疗策略中探索这一途径的增强提供了理论基础。
Although many HIV cure strategies seek to expand HIV-specific CD8(+) T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8(+) T cells. We found that virus-specific CD8(+) T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8(+) T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8(+) T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell-based therapeutic strategies for HIV.