美国约翰霍普金斯大学Francesco R. Simonetti等研究人员合作发现，特异性抗原结合在长期抗逆转录病毒治疗的患者中，诱导潜伏感染的CD4⁺ T细胞中HIV-1的表达。这一研究成果于2024年11月28日在线发表在国际学术期刊《免疫》上。

研究人员表示，尽管抗逆转录病毒治疗（ART）可以抑制HIV-1，但HIV-1仍然在潜伏感染的CD4⁺ T细胞中持续存在，阻碍了治愈的实现。抗原驱动感染细胞的增殖，从而阻止了潜伏库的衰退。然而，抗原识别与HIV-1基因表达之间的关系尚不清楚，因为大多数潜伏反转研究使用的试剂会引起非特异性的全身T细胞激活。

研究人员从接受长期ART的HIV-1感染者中分离出，对巨细胞病毒（CMV）或HIV-1 Gag抗原有反应的稀有CD4⁺ T细胞，并在与自体树突状细胞（DC）共同培养时评估T细胞的激活和HIV-1 RNA的表达，树突状细胞呈递特异性抗原。

体外呈递特异性抗原诱导了广泛的T细胞激活（CD154⁺CD69⁺细胞数中位数增加42倍），并显著提高了HIV-1转录（中位数增加4倍），主要通过诱导病毒表达较高的稀有细胞。因此，尽管HIV的潜伏病毒诱导性较低，抗原识别仍能促进HIV-1的表达，可能在ART中断时促进自发的潜伏库活跃和病毒反弹。

附：英文原文

Title: Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy

Author: Milica Moskovljevic, Filippo Dragoni, Nathan L. Board, Fengting Wu, Jun Lai, Hao Zhang, James R. White, Rebecca Hoh, Kenneth Lynn, Pablo Tebas, Karam Mounzer, Steven G. Deeks, Luis J. Montaner, Janet D. Siliciano, Robert F. Siliciano, Francesco R. Simonetti

Issue&Volume: 2024-11-28

Abstract: Despite antiretroviral therapy (ART), HIV-1 persists in latently infected CD4+ T cells, preventing a cure. Antigens drive the proliferation of infected cells, precluding latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood because most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4+ T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from people living with HIV-1 on long-term ART and assessed T cell activation and HIV-1 RNA expression upon coculture with autologous dendritic cells (DCs) presenting cognate antigens. Presentation of cognate antigens ex vivo induced broad T cell activation (median 42-fold increase in CD154+CD69+ cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity and viral rebound upon ART interruption.

DOI: 10.1016/j.immuni.2024.11.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00512-0