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International Immunology Advance Access originally published online on August 18, 2008
International Immunology 2008 20(10):1331-1342; doi:10.1093/intimm/dxn091
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Arthritis and pneumonitis produced by the same T cell clones from mice with spontaneous autoimmune arthritis

Chiaki Wakasa-Morimoto1, Tomoko Toyosaki-Maeda1, Takaji Matsutani2, Ryu Yoshida1, Shino Nakamura-Kikuoka1, Miki Maeda-Tanimura1, Hiroyuki Yoshitomi3, Keiji Hirota3, Motomu Hashimoto3, Hideyuki Masaki4, Yoshiki Fujii5, Tsuneaki Sakata1, Yuji Tsuruta1, Ryuji Suzuki6, Noriko Sakaguchi3 and Shimon Sakaguchi3

1 Discovery Research Laboratories, Shionogi & Co., Ltd, 2-5-1 Mishima Settsu-shi, Osaka 566-0022, Japan
2 Department of Cell Biology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan
3 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
4 Department of Biochemistry, Kinki University School of Medicine, 377-2 Ohno-higashi, Osakasayama-shi, Osaka 589-8511, Japan
5 Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
6 Clinical Research Center for Rheumatology and Allergy National Sagamihara Hospital, 18-1 Sakuradai, Sagamihara-shi, Kanagawa 228-8522, Japan

Correspondence to: S. Sakaguchi; E-mail: shimon{at}frontier.kyoto-u.ac.jp

SKG mice, a newly established model of rheumatoid arthritis (RA), spontaneously develop autoimmune arthritis accompanying extra-articular manifestations, such as interstitial pneumonitis. To examine possible roles of T cells for mediating this systemic autoimmunity, we generated T cell clones from arthritic joints of SKG mice. Two distinct CD8+ clones were established and both showed in vitro autoreactivity by killing syngeneic synovial cells and a variety of MHC-matched cell lines. Transfer of each clone to histocompatible athymic nude mice elicited joint swelling and histologically evident synovitis accompanying the destruction of adjacent cartilage and bone. Notably, the transfer also produced diffuse severe interstitial pneumonitis. Clone-specific TCR gene messages in the inflamed joints and lungs of the recipients gradually diminished, becoming hardly detectable in 6–11 months; yet, arthritis and pneumonitis continued to progress. Thus, the same CD8+ T cell clones from arthritic lesions of SKG mice can elicit both synovitis and pneumonitis, which chronically progress and apparently become less T cell dependent in a later phase. The results provide clues to our understanding of how self-reactive T cells cause both articular and extra-articular lesions in RA as a systemic autoimmune disease.

Keywords: animal model, interstitial lung disease, rheumatoid arthritis, T cell clone

Transmitting editor: K. Yamamoto

Received 31 March 2008, accepted 17 July 2008.


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