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

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 mi...

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Published in:The Journal of clinical investigation 2004-12, Vol.114 (11), p.1603-1611
Main Authors: Horai, Reiko, Nakajima, Akiko, Habiro, Katsuyoshi, Kotani, Motoko, Nakae, Susumu, Matsuki, Taizo, Nambu, Aya, Saijo, Shinobu, Kotaki, Hayato, Sudo, Katsuko, Okahara, Akihiko, Tanioka, Hidetoshi, Ikuse, Toshimi, Ishii, Naoto, Schwartzberg, Pamela L., Abe, Ryo, Iwakura, Yoichiro
Format: Article
Language:English
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Summary: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-α deficiency. We found that TNF-α 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-α plays an important role in activating T cells through induction of OX40.
ISSN:0021-9738
DOI:10.1172/JCI200420742