Liu Chunyan, Zheng Mengying, Zhang Tian, Fu Rong, Wang Huaquan, Wang Ting, Qi Weiwei, Shao Zonghong
The Department of Hematology, General Hospital of Tianjin Medical University, 154 Anshandao, Heping District, Tianjin, 300052, China.
The Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Int J Hematol. 2017 Oct;106(4):490-499. doi: 10.1007/s12185-017-2279-0. Epub 2017 Jun 19.
Severe aplastic anemia (SAA) is an autoimmune disease caused mainly by activated T lymphocytes. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of TNF family, which can induce apoptosis and play a significant role in the pathogenesis of many autoimmune disorders. In this study, we sought to investigate the role of TRAIL in peripheral CD8+ T cells (CTLs) from SAA patients to clarify the autoimmune mechanisms of bone marrow failure in SAA. The expression of TRAIL and TRAIL-R2 in CTLs from SAA patients and normal controls were determined by flow cytometry, real-time PCR, and western blot. Expression of perforin and granzyme B and apoptosis in CTLs were evaluated by flow cytometry. The expression of TRAIL and TRAIL-R2 in SAA patients was significantly decreased compared with controls; however, there was no statistical difference in TRAIL mRNA expression between the two groups. TRAIL expression in CTLs was negatively correlated with the expression of perforin and granzyme B, and negatively correlated with CTLs apoptosis in SAA patients. The TRAIL pathway may be responsible for abnormal CTL activation in SAA patients. Further study of TRAIL and its receptors may elucidate the pathogenesis of SAA.
重型再生障碍性贫血（SAA）是一种主要由活化的T淋巴细胞引起的自身免疫性疾病。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是TNF家族的成员，可诱导细胞凋亡，并在许多自身免疫性疾病的发病机制中发挥重要作用。在本研究中，我们试图探讨TRAIL在SAA患者外周血CD8 + T细胞（CTLs）中的作用，以阐明SAA中骨髓衰竭的自身免疫机制。通过流式细胞术、实时PCR和western blot检测SAA患者和正常对照者CTLs中TRAIL和TRAIL-R2的表达。通过流式细胞术评估CTLs中穿孔素和颗粒酶B的表达以及细胞凋亡情况。与对照组相比，SAA患者中TRAIL和TRAIL-R2的表达显著降低；然而，两组之间TRAIL mRNA表达无统计学差异。SAA患者CTLs中TRAIL表达与穿孔素和颗粒酶B的表达呈负相关，与CTLs凋亡呈负相关。TRAIL途径可能是SAA患者CTL异常活化的原因。对TRAIL及其受体的进一步研究可能阐明SAA的发病机制。
