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Interconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes

dc.contributor.authorErin M. Witkop
dc.contributor.authorKirsten Diggins
dc.contributor.authorAlice Wiedeman
dc.contributor.authorElisavet Serti
dc.contributor.authorGerald Nepom
dc.contributor.authorVivian H. Gersuk
dc.contributor.authorBryce Fuchs
dc.contributor.authorS. Alice Long
dc.contributor.authorPeter S. Linsley
dc.contributor.otherBenaroya Research Institute, Systems Immunology
dc.contributor.otherBenaroya Research Institute, Systems Immunology
dc.contributor.otherBenaroya Research Institute, Translational Immunology
dc.contributor.otherImmune Tolerance Network (ITN)
dc.contributor.otherBenaroya Research Institute, Translational Immunology
dc.contributor.otherBenaroya Research Institute, Genomics Core
dc.contributor.otherBenaroya Research Institute, Translational Immunology
dc.contributor.otherBenaroya Research Institute, Translational Immunology
dc.contributor.otherBenaroya Research Institute, Systems Immunology
dc.date.accessioned2024-06-30T11:29:42Z
dc.date.accessioned2025-10-08T08:28:11Z
dc.date.available2025-10-08T08:28:11Z
dc.date.issued01-06-2024
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/36044
dc.description.abstractAbstract Distinct Natural Killer (NK)-like CD57+ and PD-1+ CD8+ exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1+ and CD57+ Tex populations are epigenetically similar, CD57+ Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1+ and CD57+ Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57+ Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1+ Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1+, Tex-CD57+, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.
dc.language.isoEN
dc.publisherNature Portfolio
dc.subject.lccBiology (General)
dc.titleInterconnected lineage trajectories link conventional and natural killer (NK)-like exhausted CD8+ T cells beneficial in type 1 diabetes
dc.typeArticle
dc.description.pages1-14
dc.description.doi10.1038/s42003-024-06456-3
dc.title.journalCommunications Biology
dc.identifier.e-issn2399-3642
dc.identifier.oai8d3fb1a37da44494b3b4cd1c67e7d55e
dc.journal.infoVolume 7, Issue 1


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