美国埃默里大学Deanna A. Kulpa研究小组发现，CD8⁺T细胞通过重塑CD4⁺T细胞的代谢来提高其生存、静止和干性，从而促进艾滋病毒的潜伏性。这一研究成果于2023年4月7日在线发表在国际学术期刊《免疫》上。

研究人员表示，在抗逆转录病毒疗法（ART）期间，由于潜伏感染细胞的储存，HIV感染持续存在，这些细胞携带有复制能力的病毒并逃避免疫力。以前的体外研究表明，来自HIV感染者的CD8⁺T细胞可能通过非溶血机制抑制HIV的表达，但造成这种效果的机制仍不清楚。

研究人员使用了一个基于原代细胞的体外潜伏模型，并证明自体活化的CD8⁺T细胞与HIV感染的记忆性CD4⁺T细胞共同培养，促进了代谢和/或信号通路的特定变化，并导致CD4⁺T细胞存活率、静止性和干性增加。总的来说，这些途径对HIV的表达进行了负向调节，最终促进了潜伏期的建立。如前所述，研究人员观察到巨噬细胞，而不是B细胞，促进了CD4⁺T细胞的潜伏性。鉴定CD8特异性促进潜伏期活动的机制可能有利于开发消除HIV感染者病毒库的方法。

附：英文原文

Title: CD8+ T cells promote HIV latency by remodeling CD4+ T cell metabolism to enhance their survival, quiescence, and stemness

Author: Simona Mutascio, Talia Mota, Lavinia Franchitti, Ashish A. Sharma, Abigail Willemse, Sydney N. Bergstresser, Hong Wang, Maura Statzu, Gregory K. Tharp, Jared Weiler, Rafick-Pierre Sékaly, Steven E. Bosinger, Mirko Paiardini, Guido Silvestri, R. Brad Jones, Deanna A. Kulpa

Issue&Volume: 2023-04-07

Abstract: HIV infection persists during antiretroviral therapy (ART) due to a reservoir of latently infected cells that harbor replication-competent virus and evade immunity. Previous ex vivo studies suggested that CD8+ T cells from people with HIV may suppress HIV expression via non-cytolytic mechanisms, but the mechanisms responsible for this effect remain unclear. Here, we used a primary cell-based in vitro latency model and demonstrated that co-culture of autologous activated CD8+ T cells with HIV-infected memory CD4+ T cells promoted specific changes in metabolic and/or signaling pathways resulting in increased CD4+ T cell survival, quiescence, and stemness. Collectively, these pathways negatively regulated HIV expression and ultimately promoted the establishment of latency. As shown previously, we observed that macrophages, but not B cells, promoted latency in CD4+ T cells. The identification of CD8-specific mechanisms of pro-latency activity may favor the development of approaches to eliminate the viral reservoir in people with HIV.

DOI: 10.1016/j.immuni.2023.03.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00130-9