Single-cell epigenetic, transcriptional, protein, and TCR states of HIV-1-infected cells in gut

Tissue resident memory T cells (TRMs) are essential to mucosal immunity. We postulate that their long-lived tissue residency and restricted effector function promote HIV-1 persistence in human gut. We coupled single-cell-DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA, and HIV-1 RNA in gut CD4+ and CD8+ T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors. We found that BACH2, a transcription repressor that establishes long-lived memory in T cells, is the leading transcription factor that shapes gut TRMs into long-lived memory and restrains interferon-driven effector function.

组织驻留记忆T细胞（Tissue resident memory T cells, TRMs）对黏膜免疫至关重要。我们提出假说：这类细胞的长期组织驻留特性与受限的效应功能，可促进HIV-1在人体肠道内的持续感染。本研究将单细胞DOGMA-seq（single-cell-DOGMA-seq）与TREK-seq技术联用，对10名无病毒血症HIV-1感染者及5名HIV-1阴性志愿者的肠道CD4+与CD8+ T细胞进行检测，同步捕获其染色质开放性、转录组、表面蛋白、T细胞受体（T cell receptor）、HIV-1 DNA及HIV-1 RNA信息。研究发现，BACH2作为一种在T细胞中建立长期记忆表型的转录阻遏物，是塑造肠道TRMs长期记忆表型并抑制干扰素介导的效应功能的核心转录因子。