Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Mar;28(2):189-95.
doi: 10.1097/BOR.0000000000000251.

The thymus and rheumatology: should we care?

Emilie Cosway  1 , Graham Anderson, Paul Garside, Catriona Prendergast
Affiliations
Review

The thymus and rheumatology: should we care?

Emilie Cosway et al. Curr Opin Rheumatol. 2016 Mar.

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.

PubMed Disclaimer

Figures

Box 1
Box 1
no caption available
FIGURE 1
FIGURE 1
Regulation of central and peripheral tolerance. The organization of the thymus into cortex and medulla ensures that thymic selection events take place in a stepwise fashion. In the medulla, tolerance-inducing events coordinated by medullary thymic epithelial cells and dendritic cells help to remove potentially autoreactive specificities from the newly produced T-cell pool, and also result in the generation of Foxp3+ regulatory T cells. In peripheral tissues, several immune-regulatory products of Dendritic cells and Treg have been linked to the control of effector T cells that mount responses to self-antigens. Perhaps significantly, the thymus also acts as a site that supports T-cell and dendritic cell populations that enter from peripheral tissues, and evidence suggests a role for thymus recirculation in the control of T-cell tolerance. DN: CD4-CD8-, DP: CD4+CD8+; SP CD4+ or CD8+.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Forster R, Davalos-Misslitz AC, Rot A. CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 2008; 8:362–371. - PubMed
    1. Anderson G, Takahama Y. Thymic epithelial cells: working class heroes for T cell development and repertoire selection. Trends Immunol 2012; 33:256–263. - PubMed
    1. Singer A, Adoro S, Park JH. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat Rev Immunol 2008; 8:788–801. - PMC - PubMed
    1. Kurobe H, Liu C, Ueno T, et al. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Immunity 2006; 24:165–177. - PubMed
    1. Derbinski J, Gabler J, Brors B, et al. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med 2005; 202:33–45. - PMC - PubMed

Publication types

MeSH terms

Substances