Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice.

Horai R, Nakajima A, Habiro K, Kotani M, Nakae S, Matsuki T, Nambu A, Saijo S, Kotaki H, Sudo K, Okahara A, Tanioka H, Ikuse T, Ishii N, Schwartzberg PL, Abe R, Iwakura Y

Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

IL-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra(-/-) mice did not develop arthritis, and transfer of IL-1Ra(-/-) T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-alpha deficiency. We found that TNF-alpha induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-alpha plays an important role in activating T cells through induction of OX40.

Published 3 December 2004 in J Clin Invest, 114(11): 1603-11.
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