Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Academic Article uri icon

Overview

abstract

  • The immune mechanisms that mediate synovitis and joint destruction in rheumatoid arthritis (RA) remain poorly defined. Although increased levels of CD8+ T cells have been described in RA, their function in pathogenesis remains unclear. Here we perform single cell transcriptome and T cell receptor (TCR) sequencing of CD8+ T cells derived from anti-citrullinated protein antibodies (ACPA)+ RA blood. We identify GZMB+CD8+ subpopulations containing large clonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while a GZMK+CD8+ memory subpopulation comprises smaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC class I activate RA blood-derived GZMB+CD8+ T cells to expand, express cytotoxic mediators, and mediate killing of target cells. We also demonstrate that these clonally expanded GZMB+CD8+ cells are present in RA synovium. These findings suggest that cytotoxic CD8+ T cells targeting citrullinated antigens contribute to synovitis and joint tissue destruction in ACPA+ RA.

publication date

  • January 19, 2023

Research

keywords

  • Arthritis, Rheumatoid
  • Synovitis

Identity

PubMed Central ID

  • PMC9852471

Scopus Document Identifier

  • 85146617163

Digital Object Identifier (DOI)

  • 10.1093/bioinformatics/btw313

PubMed ID

  • 36658110

Additional Document Info

volume

  • 14

issue

  • 1