T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy
T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy
复制标题
DOI：
10.3109/08916939808993834
复制
发表时间：
1998-01-01
期刊：
影响因子：
3.5
通讯作者：
Wall, JR
中科院分区：
文献类型：
--
作者：
Bednarczuk, T;Kiljanski, J;Wall, JR
虽然甲状腺相关性眼病（TAO）现在被普遍认为是眼外肌和眼眶结缔组织的自身免疫性炎症性疾病，但其发病机制仍然知之甚少。最近的数据表明，T细胞和细胞外基质（ECM）蛋白之间的相互作用受损可能在炎症过程的发生和维持中起重要作用。我们在此报告了TAO患者T淋巴细胞与胶原- i （col - i）、胶原- iv （doll-IV）、纤维连接蛋白（FN）、层粘连蛋白（LM）相互作用的研究结果。通过标准外周血单个核细胞（PBMC）增殖试验，我们观察到活动性TAO患者的T细胞对col - 1的反应显著增强（平均SI = 4.5）。与正常受试者（平均SI = 1.88）、稳定的TAO患者（平均SI = 2.05）和无眼病的甲状腺自身免疫性疾病（AITD）患者（平均SI = 2.49）相比，coli对PBMC的增殖反应明显更大（Wilcoxon检验，p < 0.001）， coli刺激PBMC可能是抗原依赖性的，需要T细胞受体与胶原肽结合，而不是通过整合素介导。循环CD29(+) （β 1整合素链）T细胞的百分比；在活动期TAO患者中没有增加。此外，在cd3介导的增殖共刺激实验中，我们发现TAO和AITD患者外周血T细胞仅受到FN的共刺激，另一方面，在球后T细胞系中，我们观察到coli、Coll-IV、FN和LM对cd3介导的增殖反应的共刺激明显增强。我们得出结论，T细胞与ECM蛋白相互作用的异常，特别是col - 1可能在TAO的发病机制中起作用。
Although thyroid-associated ophthalmopathy (TAO) is now generally accepted as an autoimmune inflammatory disorder of the extraocular muscles and the orbital connective tissue, its aetiopathogenesis remains poorly understood. Recent data indicate that impaired interactions between T cells and extracellular matrix (ECM) proteins may play an important role in development and maintaining of an inflammatory process. We report here results of the study focusing on interactions between T lymphocytes and collagen-I (Coll-I), collagen-IV (doll-IV), fibronectin (FN), laminin (LM) in patients with TAO. Using a standard peripheral blood mononuclear cells (PBMC) proliferation assay, we observed a markedly enhanced T cell response to Coll-I in patients with active TAO (mean SI = 4.5). The proliferatory response to Coll-I was significantly greater (Wilcoxon test; p < 0.001) than in normal subjects (mean SI = 1.88), patients with stable TAO (mean SI = 2.05) and patients with thyroid autoimmune diseases (AITD) without ophthalmopathy (mean SI = 2.49), PBMC stimulation by Coll-I is likely to be antigen-dependent requiring engagement of the T cell receptor with collagen peptides, rather than mediated via integrins. The percentage of circulating CD29(+) (beta 1 integrin chain) T cells war; not increased in patients with active TAO. Additionally in the assay of costimulation of CD3-mediated proliferation, we found that peripheral blood T cells from patients with TAO and AITD were costimulated only by FN, On the other hand a markedly enhanced costimulation of CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed in a retrobulbar T cell line. We conclude that abnormalities in T cell interactions with ECM proteins, especially Coll-I may play a role in the pathogenesis of TAO.