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J Clin Invest. 2003 Mar;111(5):701-6.

Inducible costimulator is essential for collagen-induced arthritis.

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  • 1Department of Immunology, and. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA.

Abstract

CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.

PMID:
12618524
PMCID:
PMC151904
DOI:
10.1172/JCI17321
[PubMed - indexed for MEDLINE]
Free PMC Article
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