title: 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.
authors.affiliation: The University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia.
authors.forename: Soi-Cheng
authors.initials: SC
authors.lastname: Law
authors.affiliation: The University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia; The University of Queensland School of Medicine, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Benham
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Reid
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: The University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. Electronic address: Ranjeny.thomas@uq.edu.au.
authors.forename: Ranjeny
authors.initials: R
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D061345:Early Medical Intervention; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D017634:Self Tolerance / Q000276:immunology*
chemical_list: D001324:Autoantigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen
keywords: HLA susceptibility; Immune tolerance; Regulatory T cells; Rheumatoid arthritis; Type 1 diabetes; pMHC tetramers