Department of Pediatrics and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
Adv Exp Med Biol. 2013;756:163-8. doi: 10.1007/978-94-007-4549-0_21.
The cytotoxic T lymphocyte antigen-4 (CTLA-4) (CD152) is a basic negative regulatory molecule of T cell activation and its hypo-function is associated with severe lymphoproliferative syndrome. The aim of the present study was to evaluate the intracellular and surface expression of CTLA-4 on peripheral T cells before and after T cell activation in children with Hashimoto's thyroiditis (HT). Blood samples were obtained from 46 children: 25 with Hashimoto's thyroiditis and 21 controls free of autoimmune disease or thyroid disorders. T cell phenotype was evaluated by flow cytometry with the use of monoclonal antibodies combination: CD4- FITC/ CD28 -PC5/ CD152 -PE and CD8 -FITC/ CD28 -PC5/ CD152 -PE on T cell surface and intracellularly at baseline and after 48 h of T cell culture with the mitogen 48-PHA. We found that the number of T cells with intracellular CD152 expression was comparable in HT patients and controls at baseline and increased after 48-PHA, in CD4 subset only, in both patients and controls. However, the increase was more evident in the HT patients. The number of T cells with the surface expression of CD152 at baseline was significantly lower in the HT patients than in controls (p < 0.0002) in non-stimulated CD4+ and CD8+ T cells. After 48-PHA, surface CD152 expression in CD4+T cells increased in both groups; the increase was greater in controls. In conclusion, impaired function of CTLA-4 in HT patients may depend on the imbalance of intracellular/surface expression of CD152 in T cells.
细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)(CD152)是 T 细胞活化的基本负调控分子,其功能低下与严重的淋巴组织增生综合征有关。本研究旨在评估桥本甲状腺炎(HT)患儿 T 细胞活化前后外周 T 细胞中 CTLA-4 的细胞内和表面表达。采集 46 例儿童的血液样本:25 例桥本甲状腺炎患儿和 21 例无自身免疫性疾病或甲状腺疾病的对照者。通过使用单克隆抗体组合,采用流式细胞术评估 T 细胞表型:CD4-FITC/CD28-PC5/CD152-PE 和 CD8-FITC/CD28-PC5/CD152-PE 在 T 细胞表面和细胞内,在基础状态和用有丝分裂原 48-PHA 培养 48 小时后。我们发现,在 HT 患者和对照者中,CD152 表达的 T 细胞数量在基础状态时相似,在 CD4 亚群中仅在培养 48-PHA 后增加,在患者和对照者中均如此。然而,这种增加在 HT 患者中更为明显。在基础状态时,HT 患者的非刺激 CD4+和 CD8+T 细胞中 CD152 表面表达的 T 细胞数量明显低于对照组(p<0.0002)。在培养 48-PHA 后,两组 CD4+T 细胞表面 CD152 表达增加,对照组增加更多。总之,HT 患者 CTLA-4 功能障碍可能取决于 T 细胞中 CD152 的细胞内/表面表达失衡。