Arthritis and pneumonitis produced by the same T cell clones from mice with spontaneous autoimmune arthritis.
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.
Wakasa-Morimoto
Chiaki
C
Discovery Research Laboratories, Shionogi & Co., Ltd, 2-5-1 Mishima Settsu-shi, Osaka 566-0022, Japan.
Toyosaki-Maeda
Tomoko
T
Matsutani
Takaji
T
Yoshida
Ryu
R
Nakamura-Kikuoka
Shino
S
Maeda-Tanimura
Miki
M
Yoshitomi
Hiroyuki
H
Hirota
Keiji
K
Hashimoto
Motomu
M
Masaki
Hideyuki
H
Fujii
Yoshiki
Y
Sakata
Tsuneaki
T
Tsuruta
Yuji
Y
Suzuki
Ryuji
R
Sakaguchi
Noriko
N
Sakaguchi
Shimon
S
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007596:Joints / Q000276:immunology / Q000473:pathology; D051379:Mice; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
D001324:Autoantigens