Wen Yanling, Chen Chen, Zhou Tao, Liu Chao, Zhang Zheng, Gu Guangxiang
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Hum Immunol. 2025 Jul;86(4):111309. doi: 10.1016/j.humimm.2025.111309. Epub 2025 Apr 21.
Post-transplant lymphoproliferative disorder (PTLD) is a severe complication following liver transplantation, particularly in pediatric patients, with a high incidence rate associated with Epstein-Barr virus (EBV) infection. The immunological microenvironment of PTLD, particularly the cellular and molecular changes associated with EBV infection, remains unclear. Using scRNA-seq, we examined changes in the immune microenvironment of PBMC from pediatric liver transplant recipients across four groups: PTLD patients with EBV infection, EBV-positive non-PTLD transplant recipients, EBV-negative transplant recipients, and healthy children. PTLD patients exhibited profound immune dysregulation, marked by weakened cytotoxicity in NK cells, reduced B cell differentiation and activation, and an inflammatory shift in myeloid cells. EBV infection primarily targeted memory B cells and plasma cells in PTLD patients, with uninfected memory B cells showing impaired functional potential. Furthermore, CD8 T cells in PTLD were characterized by increased exhaustion and low cytotoxic activity. In addition, regulatory T cells in PTLD displayed enhanced suppressive functions. Our findings present an in-depth view of the immune landscape in PTLD, identifying key immune cell alterations associated with EBV infection and PTLD development. These insights could inform the development of targeted therapies aimed at restoring immune function and controlling EBV-driven lymphoproliferation in pediatric liver transplant recipients.
移植后淋巴细胞增生性疾病（PTLD）是肝移植后的一种严重并发症，尤其在儿科患者中，其发病率高且与爱泼斯坦-巴尔病毒（EBV）感染相关。PTLD的免疫微环境，特别是与EBV感染相关的细胞和分子变化，仍不清楚。我们使用单细胞RNA测序（scRNA-seq）技术，检测了儿科肝移植受者外周血单个核细胞（PBMC）免疫微环境在四组中的变化：EBV感染的PTLD患者、EBV阳性的非PTLD移植受者、EBV阴性移植受者以及健康儿童。PTLD患者表现出严重的免疫失调，其特征为自然杀伤细胞（NK细胞）的细胞毒性减弱、B细胞分化和活化减少以及髓系细胞的炎症转变。在PTLD患者中，EBV感染主要靶向记忆B细胞和浆细胞，未感染的记忆B细胞显示出功能潜力受损。此外，PTLD中的CD8 T细胞表现为耗竭增加和细胞毒性活性低。此外，PTLD中的调节性T细胞显示出增强的抑制功能。我们的研究结果深入呈现了PTLD中的免疫格局，确定了与EBV感染和PTLD发展相关的关键免疫细胞改变。这些见解可为旨在恢复免疫功能和控制儿科肝移植受者中EBV驱动的淋巴细胞增殖的靶向治疗的开发提供参考。
