Single-cell multi-omics reveals archetypal regulatory programs shared across T cell subsets.

Translationally important progenitor CD8 T cells in acute and chronic viral infection show a composite regulatory state combining a CD8 exhaustion program with a follicular helper CD4 program.

• Why it matters: T cell subsets share core immune functions, but the shared “archetypal” regulatory mechanisms that program self-renewal, expansion, cytokine production, and cytotoxicity are not well defined.
• What they did: The study integrated a single-cell multiomic scATAC+RNA-seq dataset of CD4 and CD8 T cells responding to acute and chronic viral infection with a bulk ATAC-seq compendium to infer modular epigenomic architectures and transcription factor reuse.
• The result: The resulting resource and generalizable computational framework reveal regulatory programs shared across subsets and lineages, enabling mechanistic dissection of adaptive immunity and informing immunotherapy design.