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

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE278342 | GEO | 2025/10/13

REPOSITORIES: GEO

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