Identification of self-antigen-specific T cells reflecting loss of tolerance in autoimmune disease underpins preventative immunotherapeutic strategies in rheumatoid arthritis

Abstract

Despite treatment advances, rheumatoid arthritis (RA) is still associated with significant disability, decreased work capacity, and reduced life expectancy. Effective immunotherapies to restore immune tolerance promise greater specificity, lower toxicity, and a longer-term solution to controlling and preventing RA. Design of effective therapies requires a fundamental understanding of the critical immunopathogenetic pathways in RA. This article reviews advances in the understanding of self-antigen-specific T cells in autoimmune diseases including RA and type 1 diabetes, which bring exciting insights to the mechanisms underpinning loss of tolerance and how tolerance could be restored for disease prevention in the preclinical or recent-onset period.

Keywords: HLA susceptibility; Immune tolerance; Regulatory T cells; Rheumatoid arthritis; Type 1 diabetes; pMHC tetramers.