Liu Shenglin, Zhang Qian, Huang Dongli, Zhang Wenli, Zhong Fengluan, Feng Jia, Chen Xueru, Meng Qingxiang, Chen Xiaofan, Zhang Wei, Zhang Hongyu
Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, 518036, China.
Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China.
Ann Hematol. 2017 Apr;96(4):665-680. doi: 10.1007/s00277-016-2911-8. Epub 2017 Jan 14.
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.
爱泼斯坦-巴尔病毒（EBV）原发性感染通常无症状，但有时会发展为传染性单核细胞增多症（IM）。偶尔，一些人会在潜在免疫缺陷的情况下发生慢性活动性EBV感染（CAEBV），这属于EBV相关淋巴增殖性疾病（EBV LPD）的连续谱系，临床表现各异且死亡率高。T细胞介导的免疫反应在EBV感染的疾病演变中起关键作用，这一点已得到充分证实。最近，T细胞受体（T细胞受体β（TCRβ））高变互补决定区3（CDR3）片段的高通量测序已成为评估T细胞库的一种敏感方法。在本研究中，我们全面描述了IM患者（n = 6）、CAEBV患者（n = 5）和EBV血清阳性对照者（n = 5）外周血TCRβ库的多样性。与健康的EBV血清阳性对照者相比，IM患者和CAEBV患者外周血TCRβ库多样性均显著降低，基本上包括库广度变窄、克隆高度扩增以及CDR3长度分布偏态。然而，IM患者和CAEBV患者之间无显著差异。此外，我们观察到TRBV/TRBJ使用和组合存在一些与疾病相关的偏好，以及不同组（独特或重叠）共享的许多T细胞克隆参与公共T细胞反应，这为不同的疾病演变提供了更详细的见解。
