Abstract
PURPOSE OF REVIEW: 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).
RECENT FINDINGS: 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.
SUMMARY: 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.
Original language | English |
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Pages (from-to) | 189–195 |
Journal | Current Opinion in Rheumatology |
Volume | 28 |
Issue number | 2 |
Early online date | 8 Jan 2016 |
DOIs | |
Publication status | Published - Mar 2016 |
Keywords
- dendritic cell
- T cell
- thymus
- tolerance
- Treg