title: The thymus and rheumatology: should we care?
abstract: OBJECTIVE
  The purpose of this review is to discuss the mechanisms of central and peripheral tolerance in relation to T-cell mediated autoimmunity in rheumatoid arthritis (RA).
  
  
  RESULTS
  The well established association between major histocompatibility complex class II and RA has led us to understand that T cells, and the adaptive immune response, are important in the pathogenesis of disease. In order for autoimmune disease to develop, there is a breach of tolerance to self antigen and the mechanisms of both central and peripheral tolerance aim to prevent this. Here, we review evidence from mouse models indicating that alterations in T-cell receptor signalling thresholds during thymic selection may be linked to the escape of T cells that mediate autoimmune arthritis. In addition, we summarize the role of dendritic cells and Foxp3+ regulatory T cells in both peripheral and thymic tolerance, and highlight their relevance to what we know about the aetiology of RA.
  
  
  CONCLUSIONS
  Mechanisms of central tolerance in the thymus and peripheral tolerance are in place to control autoreactive T cells and to prevent the development of autoimmune disease. We anticipate that a better understanding of these mechanisms will lead to the development of better, antigen-specific therapeutics to restore tolerance.
authors.affiliation: aMRC Centre for Immunology, Institute for Immunology and Immunotherapy, Medical School, University of Birmingham, Birmingham bCentre for Immunobiology, Institute of Infection, Immunology and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cosway
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: Catriona
authors.initials: C
authors.lastname: Prendergast
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
chemical_list: D001324:Autoantigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22