Cytotoxic Cd8 T Cells Target Citrullinated Antigens In Rheumatoid Arthritis Jaeseung Moon 1 by Jae-seung Moon 1, 2, 11, Shady Younis 1, 2, 3, 11, Nitya S. Ramadoss1, 2, instant download after payment.

The immune mechanisms that mediate synovitis and joint destruction inrheumatoid arthritis (RA) remain poorly defined. Although increased levels ofCD8+ T cells have been described in RA, their function in pathogenesis remainsunclear. 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 largeclonal lineage expansions that express cytotoxic and tissue homing transcriptional programs, while a GZMK+CD8+ memory subpopulation comprisessmaller clonal expansions that express effector T cell transcriptional programs. We demonstrate RA citrullinated autoantigens presented by MHC classI activate RA blood-derived GZMB+CD8+ T cells to expand, express cytotoxicmediators, and mediate killing of target cells. We also demonstrate that theseclonally expandedGZMB+CD8+ cells are present in RA synovium. These findingssuggest that cytotoxic CD8+ T cells targeting citrullinated antigens contributeto synovitis and joint tissue destruction in ACPA+ RA.