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

Horai, Reiko; Nakajima, Akiko; Habiro, Katsuyoshi; Kotani, Motoko; Nakae, Susumu; Matsuki, Taizo; Nambu, Aya; Saijo, Shinobu et al. · J Clin Invest · 2004

basic_science · Level V

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Abstract

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.

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