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

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 Overall design: live CD8ß+CD44hiCD45.1+Va2+ P14 cells from each sample (pooled organs from 20 Arm-infected mice or 20 C13 infected mice) d30 post infection were sorted and stained with TotalSeq-A Oligos and custom pool of antibody derived tags.Also TEA sequencing on these samples for GEX+ATAC