GD患者外周血CD4^+CD28-T细胞亚群的表型特征及临床意义

Phenotypic characteristics of the CD4^+CD28^-T cell subsets in peripheral blood of patients with Graves disease and its clinical significance

检测Graves病(GD)患者外周血CD4^+CD28-T细胞水平及其表面CD45RO/CD45RA及ICOS的表达,探讨CD4^+ CD28-T细胞亚群在GD免疫致病机制中的作用。采用三色荧光抗体染色及流式细胞术检测了42例初发GD患者和30例健康者外周血中CD4^+CD28-T细胞的百分率及其表面CD45RO/CD45RA和ICOS表达水平,同时检测其甲状腺功能并进行相关性分析。结果GD患者外周血中CD4^+CD28-T细胞百分率明显高于健康对照组,并高表达ICOS分子,与FT3水平显著正相关;与健康对照组相比,GD患者CD4^+CD28^-CD45RO^+T细胞百分率也显著增高,而CD4^+CD28^-CD45RA^+T细胞呈下降趋势,FT3、FT4水平与CD4^+CD28-T细胞表面CD45RO的表达率呈正相关,而FT3水平与CD45RA表达呈负相关。结论GD患者外周血CD4^+CD28^-T细胞异常增高,表面高表达ICOS分子,具有记忆性细胞的表型特征,与甲状腺功能异常有一定的相关性,CD4^+CD28-T细胞可能是参与GD免疫病理反应的自身反应性T细胞。

To explore the effect of the CD4^＋CD28^- T cell subsets in the immune pathogenesis of Graves disease（GD）, the expression levels of these T cell subsets and their surface CD45RO/CD45RA and co-stimulatory molecule ICOS in peripheral bloods of patients with GD were determined by using the three-colored flow cytometry in 42 GD patients and 30 healthy volunteers. Meanwhile, function of thyroid gland in GD patients was detected to perform the correlation analysis. It was demonstra- ted that the percentages of the CD4^＋CD28^-T cell subsets in peripheral bloods of GD patients were significantly higher than those of the healthy volunteers with high expression of the ICOS molecule. In GD patients, the percentage of the CD4^＋CD28^- CD45RO^＋ T cells was also significantly increased, however, that of the CD4^＋CD28^- CD45RA^＋ T cells showed a tendency to decline. In addition, the levels of FT3 and FT4 positively correlated with the expression rate or the CD4^＋CD28^- CD45RO^＋ T cells, whereas, the level of FT3 negatively correlated with the expression of the CD4^＋CD28^- CD45RA^＋ T cells. It is evident that the CD4^＋CD28^-T cells in peripheral bloods of patients with Graves disease increase aberrantly with a concordant increase of the co-stimulatory molecule ICOS, suggesting that these T cell subsets exhibit the phenotypic characteristics of T memory cells with definite correlation to the dysfunction of thyroid gland, and they may be the auto-reactive T cells involved in the immune pathogenesis of Graves disease.