Spontaneous lymphocyt ic thyroiditis in interferon regulatory factor-1 deficient non-obese diabetic mice.
Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon-mediated immune reaction, CD8+ T cell differentiation and development of T helper 1 immune reaction. We have recently demonstrated that IRF-1 is pivotal in iodine-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice. However, it remains unclear whether the mechanism involved in spontaneous LT is identical with iodine-induced LT in NOD mice. To determine the role of IRF-1 in spontaneous LT, we used IRF-1 deficient NOD mice as well as IRF-1 +/+ and +/- mice which were free from treatments for LT induction, and LT was evaluated at 24 weeks of age. IRF-1 +/+, +/- and -/- mice developed LT spontaneously, and there were no differences among the 3 IRF-1 genotypes in the incidence and severity of LT. Whereas both CD4+ and CD8+ T cells were present in the diseased thyroid of IRF-1 +/+ mice, CD8+ T cells were absent in the thyroid of IRF-1 -/- mice. MHC class II antigen expression was induced in the inflamed thyroid of IRF-1 -/- mice comparable to IRF-1 +/+ mice. There was a selective reduction in the number of CD8+ T cells in the spleen of IRF-1 -/- mice. IFNgamma production, but not IL-10, by concanavalin A-stimulated splenocytes was significantly reduced in IRF-1 deficient mice. These results suggest that IRF-1 plays only a minor role in spontaneous LT in NOD mice and, furthermore, the mechanism involved in spontaneous LT is different from that of iodine-induced LT in NOD mice.
Hoshikawa
S
S
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Mori
K
K
Tani
J
J
Jin
Z
Z
Nakagawa
Y
Y
Satoh
J
J
Ito
S
S
Yoshida
K
K
D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D005838:Genotype; D050856:Interferon Regulatory Factor-1; D051379:Mice; D016688:Mice, Inbred NOD; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology* / Q000662:veterinary
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins