Tandon N, Weetman A P
Department of Medicine, University of Sheffield.
J R Coll Physicians Lond. 1994 Jan-Feb;28(1):10-8.
Autoimmune thyroid disease is the archetype of organ-specific autoimmune disorders and shares with them T cell dependence. The observation that thyroid cells in autoimmune thyroid disease express the major histocompatibility complex molecule HLA-DR led to the hypothesis that they could present antigen and initiate or maintain the autoimmune process. However, functional experiments, and recent evidence indicating that provision of a co-stimulatory signal is also essential for efficient antigen presentation, argue against such a role. The analysis of T cell responses to two major thyroid antigens, thyroid peroxidase and the thyroid stimulating hormone receptor, reveals a heterogeneity both within and between patients, and intrathyroidal T cells show diverse usage of T cell receptor genes. Therefore, any strategy that uses modified peptides, monoclonal antibodies against specific T cell receptor molecules, or T cell vaccination for the purpose of treating thyroid autoimmunity is unlikely to succeed.
自身免疫性甲状腺疾病是器官特异性自身免疫性疾病的典型代表,与其他此类疾病一样具有T细胞依赖性。自身免疫性甲状腺疾病中的甲状腺细胞表达主要组织相容性复合体分子HLA - DR这一观察结果,引发了这样一种假说,即它们能够呈递抗原并启动或维持自身免疫过程。然而,功能实验以及最近表明提供共刺激信号对于有效抗原呈递也至关重要的证据,反驳了这种作用。对T细胞对两种主要甲状腺抗原(甲状腺过氧化物酶和促甲状腺激素受体)的反应分析显示,患者体内和患者之间均存在异质性,甲状腺内的T细胞显示出T细胞受体基因的多样使用情况。因此,任何旨在治疗甲状腺自身免疫性疾病而使用修饰肽、针对特定T细胞受体分子的单克隆抗体或T细胞疫苗接种的策略都不太可能成功。