Department of Medicine, University of California, San Francisco, San Francisco, California.
Gladstone-UCSF Institute for Genomic Immunology, San Francisco, CA, USA.
Curr Opin HIV AIDS. 2022 Sep 1;17(5):315-324. doi: 10.1097/COH.0000000000000748. Epub 2022 Jul 1.
Immunological studies of spontaneous HIV and simian virus (SIV) controllers have identified virus-specific CD8 + T cells as a key immune mechanism of viral control. The purpose of this review is to consider how knowledge about the mechanisms that are associated with CD8 + T cell control of HIV/SIV in natural infection can be harnessed in HIV remission strategies.
We discuss characteristics of CD8 + T-cell responses that may be critical for suppressing HIV replication in spontaneous controllers comprising HIV antigen recognition including specific human leukocyte antigen types, broadly cross-reactive T cell receptors and epitope targeting, enhanced expansion and antiviral functions, and localization of virus-specific T cells near sites of reservoir persistence. We also discuss the need to better understand the timing of CD8 + T-cell responses associated with viral control of HIV/SIV during acute infection and after treatment interruption as well as the mechanisms by which HIV/SIV-specific CD8 + T cells coordinate with other immune responses to achieve control.
We propose implications as to how this knowledge from natural infection can be applied in the design and evaluation of CD8 + T-cell-based remission strategies and offer questions to consider as these strategies target distinct CD8 + T-cell-dependent mechanisms of viral control.
目的综述:对自发性 HIV 和猴免疫缺陷病毒(SIV)控制器的免疫研究已经确定了病毒特异性 CD8+T 细胞是控制病毒的关键免疫机制。本综述旨在探讨与自然感染中 CD8+T 细胞控制 HIV/SIV 相关的机制的知识如何可以应用于 HIV 缓解策略。
最新发现:我们讨论了可能对抑制自然控制器中 HIV 复制至关重要的 CD8+T 细胞反应的特征,这些控制器包括 HIV 抗原识别,包括特定的人类白细胞抗原类型、广泛的交叉反应性 T 细胞受体和表位靶向、增强的扩增和抗病毒功能,以及病毒特异性 T 细胞在储存库持续存在部位附近的定位。我们还讨论了需要更好地了解急性感染期间和治疗中断后与 HIV/SIV 病毒控制相关的 CD8+T 细胞反应的时机,以及 HIV/SIV 特异性 CD8+T 细胞如何与其他免疫反应协调以实现控制的机制。
总结:我们提出了从自然感染中获得的这些知识如何应用于设计和评估基于 CD8+T 细胞的缓解策略的建议,并提供了一些问题供考虑,因为这些策略针对不同的依赖 CD8+T 细胞的病毒控制机制。