REVIEW - Thymic Hassall's corpuscles, regulatory T-cells, and RA

September 25, 2010

Semin Arthritis Rheum. 2010 Apr;39(5):347-55. Epub 2008 Oct 29.

Thymic Hassall's corpuscles, regulatory T-cells, and rheumatoid arthritis.

Berthelot JM, le Goff B, Maugars Y.

Rheumatology Unit, Nantes University Hospital, Nantes, France.

Abstract

OBJECTIVE: To review evidence for the involvement of thymic Hassall's

corpuscles (HC) in the pathogenesis of rheumatoid arthritis (RA).

METHODS: We used PubMed to search for articles dedicated to the

involvement of HC and regulatory T-cells (Tregs) in the pathogenesis

of RA, and articles on thymic B-cells.

RESULTS: Tregs are central players mediating tolerance to self. The

functional defects in Tregs observed in patients with active RA may

contribute to RA pathogenesis, promoting the premature

immunosenescence of T-cells. This may partly explain the persisting

expansion of CD4+ effector T-cell clones in peripheral blood, as well

as the parallel improvement of RA activity and numbers of Tregs

observed in the third trimester of pregnancy. HC play a major role in

the selection of natural Tregs in the thymus, potentially altering the

peripheral Tregs repertoire. The promiscuous expression of

tissue-specific antigens by thymic medullary epithelial cells shapes

the repertoire of natural Tregs. Thus, the presence of 2 major RA

autoantigens (immunoglobulins and filaggrin) in the cytoplasm of

normal human HC is puzzling, particularly given that thymic B-cells

are also concentrated around HC, where CD55 (DAF) and CD59 are

strongly expressed. Defects in HC could alter the repertoire of thymic

B-cells and Tregs in RA patients, promoting the onset of this

disorder.

CONCLUSION: The identification of other joint-specific antigens, like

gp-39, in HC and medullary epithelial cells, would provide new

insights into the mechanisms of RA pathogenesis and may lead to more

specific and physiologic methods of immunomodulation.

PMID: 18973928

Not an MD

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