TNF-alpha 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 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.
Horai
Reiko
R
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Nakajima
Akiko
A
Habiro
Katsuyoshi
K
Kotani
Motoko
M
Nakae
Susumu
S
Matsuki
Taizo
T
Nambu
Aya
A
Saijo
Shinobu
S
Kotaki
Hayato
H
Sudo
Katsuko
K
Okahara
Akihiko
A
Tanioka
Hidetoshi
H
Ikuse
Toshimi
T
Ishii
Naoto
N
Schwartzberg
Pamela L
PL
Abe
Ryo
R
Iwakura
Yoichiro
Y
D000818:Animals; D018501:Antirheumatic Agents / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D018501:Antirheumatic Agents; D019013:CD40 Antigens; D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; C505717:Tnfrsf4 protein, mouse; D014409:Tumor Necrosis Factor-alpha