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

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Tissue-resident memory T cells (Trms) are crucial for mucosal immunity.
• Long-lived Trms and their restricted function may promote persistent infections like HIV-1 in the gut.

Purpose of the Study:

• To investigate the role of gut Trms in HIV-1 persistence.
• To identify factors shaping Trm characteristics and their susceptibility to HIV-1 infection.

Main Methods:

• Utilized single-cell DOGMA-seq and TREK-seq to analyze gut CD4+ and CD8+ T cells from HIV-1+ and HIV- individuals.
• Assessed chromatin accessibility, transcriptome, surface proteins, TCRs, and HIV-1 nucleic acids.
• Investigated the function of the transcription factor BACH2 in Trm differentiation and HIV-1 infection.

Main Results:

• BACH2 was identified as a key transcription factor shaping gut Trms into long-lived memory cells with restrained effector function.
• BACH2-ablation altered Trm memory phenotypes.
• HIV-1 preferentially infected and persisted in BACH2-high gut Trms.
• HIV-1-specific CD8+ T cells showed tissue residency and exhaustion markers, indicating immune evasion.

Conclusions:

• HIV-1 persists in the gut within long-lived Trms shaped by BACH2.
• BACH2 plays a critical role in maintaining Trm longevity and influencing HIV-1 persistence in the gut mucosa.