美国耶鲁大学医学院Ya-Chi Ho团队的论文发现了转录因子BACH2塑造组织驻留记忆T细胞程序以促进HIV-1的持久性。相关论文于2025年8月21日发表在《免疫学》杂志上。

该课题组研究人员假设它们在组织中的长期驻留和有限的效应功能促进了HIV-1在肠道中的持续存在。课题组研究人员将单细胞DOGMA-seq和TREK-seq偶联，在10例病毒血症HIV-1⁺个体和5例HIV-1患者的肠道CD4⁺和CD8⁺ T细胞中捕获染色质可及性、转录组、表面蛋白、T细胞受体（TCRs）、HIV-1 DNA和HIV-1 RNA。捐助者。BACH2是一种在T细胞中建立长期记忆的转录抑制因子，是将肠道Trms塑造成长期记忆并抑制干扰素驱动效应因子功能的关键转录因子。BACH2消融将长寿命的中枢记忆T细胞转移到效应记忆。HIV-1感染细胞主要存在于BACH2高的Trms中，并且HIV-1在体外的肠道Trms中优先感染并持续存在。HIV-1特异性CD8⁺ T细胞表现出组织驻留和衰竭的表观遗传疤痕，促进了肠道中HIV-1免疫逃避。总的来说，他们的发现表明HIV-1在BACH2形状的长寿命Trms中持续存在。

据介绍，组织常驻记忆T细胞（Trms）对粘膜免疫至关重要。

附：英文原文

Title: Transcription factor BACH2 shapes tissue-resident memory T cell programs to promote HIV-1 persistence

Author: Yulong Wei, Haocong Katherine Ma, Michelle E. Wong, Hyein Back, Emmanouil Papasavvas, Karam Mounzer, Faten Aberra, Ricardo Morgenstern, Pablo Tebas, Liza Konnikova, Luis J. Montaner, Ya-Chi Ho

Issue&Volume: 2025-08-21

Abstract: Tissue-resident memory T cells (Trms) are essential for mucosal immunity. We postulated that their long-lived tissue residency and restricted effector function promoted HIV-1 persistence in the gut. We coupled single-cell DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptors (TCRs), HIV-1 DNA, and HIV-1 RNA in gut CD4+ and CD8+ T cells from ten aviremic HIV-1+ individuals and five HIV donors. BACH2, a transcriptional repressor that establishes long-lived memory in T cells, was a key transcription factor that shaped gut Trms into long-lived memory and restrained interferon-driven effector function. BACH2-ablation shifted long-lived central memory T cells to effector memory. HIV-1-infected cells were predominantly identified among BACH2high Trms, and HIV-1 preferentially infected and persisted in gut Trms in vitro. HIV-1-specific CD8+ T cells exhibited tissue residency and epigenetic scars of exhaustion, contributing to HIV-1 immune evasion in the gut. Overall, our findings indicate that HIV-1 persists in BACH2-shaped long-lived Trms.

DOI: 10.1016/j.immuni.2025.07.022

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00331-0