Choi E-W, Shin I-S, Bhang D-H, Lee D-H, Bae B-K, Kang M-S, Kim D-Y, Hwang C-Y, Lee C-W, Youn H-Y
Department of Veterinary Internal Medicine, Seoul National University, Seoul, Korea.
Clin Exp Immunol. 2006 Oct;146(1):101-8. doi: 10.1111/j.1365-2249.2006.03187.x.
To elucidate the hormonal change and alteration in cytokine expression in peripheral blood mononuclear cells (PBMC) during the early stage of autoimmune thyroiditis, we have developed a canine model of this disease, in which normal dogs were immunized with bovine thyroglobulin (Tg) and/or canine thyroid extract. Serum samples were collected weekly, anti-canine Tg antibody was measured by enzyme-linked immunosorbent assay (ELISA) and thyroid stimulating hormone (TSH) and total T4 levels by radioimmunoassay. We also assayed T lymphocyte proliferation in response to Tg, as well as measuring cytokine mRNA by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). All six dogs immunized with bovine Tg had both canine Tg autoantibody and anti-T4 antibody. When the sample from the highest TgAA titre time-point was compared with baseline the expression of mRNA encoding the Th1-type cytokine such as interferon (IFN)-gamma, interleukin (IL)-18 and IL-15 was increased during the development of autoimmune thyroiditis. Expression of the Th2-type cytokine, IL-6 showed minimal change and IL-4 expression was not detected in any of the samples. Expression of the T suppressive cytokine, IL-10 and transforming growth factor (TGF)-beta was increased in the presence of antigen stimulation. These findings suggest that, although autoimmune thyroiditis is an organ-specific autoimmune disease, systemic cytokine mRNA expression is also changed.
为了阐明自身免疫性甲状腺炎早期外周血单个核细胞(PBMC)中激素变化及细胞因子表达的改变,我们建立了该疾病的犬模型,用牛甲状腺球蛋白(Tg)和/或犬甲状腺提取物对正常犬进行免疫。每周采集血清样本,采用酶联免疫吸附测定(ELISA)检测抗犬Tg抗体,采用放射免疫测定法检测促甲状腺激素(TSH)和总T4水平。我们还检测了Tg刺激下T淋巴细胞的增殖情况,并通过半定量逆转录-聚合酶链反应(RT-PCR)测定细胞因子mRNA。所有6只经牛Tg免疫的犬均产生了犬Tg自身抗体和抗T4抗体。将最高TgAA滴度时间点的样本与基线样本进行比较时发现,在自身免疫性甲状腺炎发展过程中,编码Th1型细胞因子如干扰素(IFN)-γ、白细胞介素(IL)-18和IL-15的mRNA表达增加。Th2型细胞因子IL-6的表达变化极小,且在任何样本中均未检测到IL-4的表达。在抗原刺激下,T抑制性细胞因子IL-10和转化生长因子(TGF)-β的表达增加。这些发现表明,尽管自身免疫性甲状腺炎是一种器官特异性自身免疫性疾病,但全身细胞因子mRNA表达也会发生变化。