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

ABSTRACT: 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. C

SUBMITTER: Witkop EM 

PROVIDER: S-EPMC11211332 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature