Anti-120-kDa alpha-fodrin immune response with Th1-cytokine profile in the NOD mouse model of Sjögren's syndrome.
Our recent study suggested that the 120-kDa alpha-fodrin molecule may be an important autoantigen in the pathogenesis of Sjögren's syndrome, and anti-120-kDa alpha-fodrin antibodies have been detected in patients with Sjögren's syndrome. Here we have analyzed anti-120-kDa alpha-fodrin immune responses during development of spontaneous autoimmune sialadenitis in NOD mice as a model of Sjögren's syndrome. We found specific autoantibody production against 120-kDa alpha-fodrin, and its production correlated closely with autoimmune sialadenitis. A specific T cell response of splenocytes against the 120-kDa alpha-fodrin autoantigen was observed in NOD mice from the early onset of autoimmune sialadenitis. In addition, production in vitro by splenic T cells of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), but not IL-4, was detected by enzyme-linked immunosorbent assays. We found up-regulation of local cytokine genes, including those of Th1 type (IL-1beta, TNF-alpha, IL-2, IFN-gamma, IL-6), as well as IL-10 and IL-12(p40), in the tissue-infiltrating cells during the course of autoimmune sialadenitis. These findings suggest that in spontaneous autoimmune sialadenitis in NOD mice, there may be a specific anti-120-kDa alpha-fodrin immune response in the development of autoimmune lesions resembling human Sjögren's syndrome, and that the autoreactive Th1 cells possess an up-regulated cytokine profile besides IL-10 and IL-12.
Yanagi
K
K
Department of Pathology, Tokushima University School of Dentistry, Japan.
Ishimaru
N
N
Haneji
N
N
Saegusa
K
K
Saito
I
I
Hayashi
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008840:Microfilament Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D012469:Salivary Glands / Q000276:immunology; D012793:Sialadenitis; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013049:Spectrin
D001323:Autoantibodies; D002352:Carrier Proteins; D016207:Cytokines; D008840:Microfilament Proteins; D013049:Spectrin