Zheng R Q, Abney E R, Grubeck-Loebenstein B, Dayan C, Maini R N, Feldmann M
Charing Cross Sunley Research Centre, Hammersmith, London, UK.
J Autoimmun. 1990 Dec;3(6):727-36. doi: 10.1016/s0896-8411(05)80039-3.
Human endocrine thyroid epithelial cells (TEC) from autoimmune thyroiditis which express HLA Class II antigens have been shown to present autoantigens to T cells for a TEC-specific immune response. Since the initiation of a specific immune response also involves antigen-receptor independent interactions between accessory molecules, such as lymphocyte function-associated antigen-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3) with CD2, it was of interest to determine whether TEC can express the adhesion molecules (ICAM-1 and LFA-3) which augment the efficiency of antigen presentation. Cultured TEC were studied for their expression of ICAM-1 and LFA-3 by immunofluorescence. Those derived from Graves' disease expressed these molecules after stimulation with recombinant human interferon-gamma (IFN gamma) or with recombinant human tumour necrosis factor-alpha (TNF alpha). However, using the same stimuli, TEC from non-toxic goitre were induced to express ICAM-1, but not LFA-3. To establish whether ICAM-1 and LFA-3 on TEC were expressed in vivo during the disease process, antibodies against these molecules were incubated with frozen sections of autoimmune thyroiditis, including Graves' and Hashimoto's diseases, and non-toxic goitre. Both ICAM-1 and LFA-3 were highly expressed in the autoimmune diseases, but not in non-toxic goitre. These findings establish that TEC are able to express adhesion molecules and suggest the possible involvement of these adhesion molecules in the TEC-specific immune response in autoimmune thyroiditis.
来自自身免疫性甲状腺炎且表达HLA II类抗原的人内分泌甲状腺上皮细胞(TEC)已被证明可将自身抗原呈递给T细胞,以引发TEC特异性免疫反应。由于特异性免疫反应的启动还涉及辅助分子之间抗原受体非依赖性相互作用,如淋巴细胞功能相关抗原-1(LFA-1)与细胞间黏附分子-1(ICAM-1)以及淋巴细胞功能相关抗原-3(LFA-3)与CD2之间的相互作用,因此确定TEC是否能表达增强抗原呈递效率的黏附分子(ICAM-1和LFA-3)具有重要意义。通过免疫荧光研究培养的TEC中ICAM-1和LFA-3的表达。来自格雷夫斯病的TEC在用重组人干扰素-γ(IFNγ)或重组人肿瘤坏死因子-α(TNFα)刺激后表达这些分子。然而,使用相同的刺激,来自非毒性甲状腺肿的TEC被诱导表达ICAM-1,但不表达LFA-3。为了确定疾病过程中TEC上的ICAM-1和LFA-3是否在体内表达,将针对这些分子的抗体与自身免疫性甲状腺炎(包括格雷夫斯病和桥本氏病)以及非毒性甲状腺肿的冰冻切片孵育。ICAM-1和LFA-3在自身免疫性疾病中均高度表达,但在非毒性甲状腺肿中不表达。这些发现证实TEC能够表达黏附分子,并提示这些黏附分子可能参与自身免疫性甲状腺炎中TEC特异性免疫反应。