Department of Hematology, General Hospital of Tianjin Medical University, Tianjin, China.
Biomed Res Int. 2018 May 14;2018:6413815. doi: 10.1155/2018/6413815. eCollection 2018.
Severe aplastic anemia (SAA) is characterized by pancytopenia and failure of hematopoietic function and is caused by excessive functioning of cytotoxic T lymphocytes (CTLs). EBNA-1, a nucleoprotein of the Epstein Barr virus (EBV), can influence the proliferation and function of lymphocytes. We therefore tested the number of EBV copies in the CD8+ T cells of 27 patients with SAA and 10 healthy control subjects and observed the influences of EBNA-1 upon the CD8+ T cells of patients with SAA. The results showed that more EBV copies were found in the CD8+ T cells of patients with untreated SAA than in patients with SAA in remission or in the healthy control subjects. Their copy number was positively correlated with the expression of granzyme B and perforin, the secretion level of interferon- in CD8+ T cells, and the viability of CD8+ T cells, whereas no correlation was seen between the copy number and the interleukin 4 secretion level or the apoptosis rate. Meanwhile, the expression of granzyme B and perforin was reduced after EBNA-1 gene knockdown, whereas the interferon- secretion level and cell viability declined. Therefore, we infer that EBV infection may be a factor in the activation of CTLs and in damaging the bone marrow hematopoietic function of patients with SAA.
重型再生障碍性贫血(SAA)以全血细胞减少和造血功能衰竭为特征,是由细胞毒性 T 淋巴细胞(CTLs)过度活跃引起的。EBV 的核蛋白 EBNA-1 可影响淋巴细胞的增殖和功能。因此,我们检测了 27 例 SAA 患者和 10 例健康对照者的 CD8+T 细胞中 EBV 拷贝数,并观察了 EBNA-1 对 SAA 患者 CD8+T 细胞的影响。结果表明,未经治疗的 SAA 患者的 CD8+T 细胞中 EBV 拷贝数高于缓解期 SAA 患者和健康对照者。其拷贝数与 CD8+T 细胞中颗粒酶 B 和穿孔素的表达、干扰素-的分泌水平以及 CD8+T 细胞的活力呈正相关,而与白细胞介素 4 的分泌水平或细胞凋亡率无相关性。同时,EBNA-1 基因敲低后颗粒酶 B 和穿孔素的表达减少,而干扰素-的分泌水平和细胞活力下降。因此,我们推断 EBV 感染可能是激活 CTLs 并损害 SAA 患者骨髓造血功能的一个因素。