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Divergent programming and nonreciprocal plasticity of tissue resident exhaustedand memory CD8+T cell lineages

GSE278342 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other 8 samples Submitted 2025/10/13 Platform GPL24247
Summary
persistent antigen stimulation during chronicinfectioninduces apopulationof CD39hiCD69+CD103+/–Hobit+/–tissue-resident TEXcells in non-lymphoid tissuesthataredevelopmentally distinctfrombona fideTRMcells generated afteracutelyresolvedinfection.Tissue-resident TEXcells had reduced function and limited developmentalplasticity compared to TRMcells. Moreover, tissue-resident TEXandbona fideTRMcells weregoverned bydistinct transcriptional and epigenetic programs indicating divergent developmentalpaths.Indeed, whereasestablishedTRMcellscould giverise to secondaryantigen-independentmemory CD8+T cellsafter acute infectionas well as multiple subsets of TEXcells including TCF1+progenitorsduring chronic restimulation,establishedTEXcells were unable to form TRMcells andrequired ongoing antigen stimulation to efficientlyacquire residency features.Moreover,bona fideTRMdevelopedindependently of Tox, whereasTox controlled induction of residency-associatedmolecules in developing CD69+CD103+/–tissue-resident TEXcells and was essential for theiraccumulation in nonlymphoid tissues
Published in
Tissue-resident exhausted and memory CD8(+) T cells have distinct ontogeny, function and role in disease
Park SL, Painter MM, Manne S et al. · Nature immunology 2026 · PMID 41461986 · doi:10.1038/s41590-025-02352-y
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Also filed as BioProject PRJNA1166687 and SRA study SRP535491. Searching any of these in the dataset finder brings you back here.

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