人类疱疹病毒EBV与淋巴瘤的产生密切相关。T细胞免疫反应在调控EBV相关的淋巴瘤产生中起了非常重要的作用，其中最重要的机制之一就是通过T细胞杀伤的效应分子CD95死亡受体介导的细胞凋亡信号。虽然很多EBV相关的淋巴瘤细胞表面表达高水平的CD95，但是它们对CD95介导的凋亡信号有抗性，相应的能逃逸T细胞的杀伤。我们的前期研究结果表明，在这些高表达CD95受体且对CD95介导的凋亡信号有抗性的EBV相关淋巴瘤细胞中，CD95介导的非细胞凋亡信号抑制了EBV从潜伏到裂解复制的再激活过程，从而有助于EBV逃逸宿主免疫系统的识别，有利于淋巴瘤细胞的生存。CD95的配体在生理条件下存在两种形式，切割形式的配体和膜结合的配体。本项目进一步研究这两种配体介导的CD95信号通路在EBV相关淋巴瘤中的作用机制，解析不同类型的淋巴瘤细胞的具体免疫反应，为提供更特异的免疫相关治疗提供新的靶点和策略。

Human gammaherpesvirus Epstein-Barr Virus (EBV) is tightly associated with different types of lymphomas. T cells play an important role in controlling EBV-associated lymphoma development and growth, mainly regulated by CD95 dead receptor-mediated apoptosis and effector molecule perforin. Although many EBV-associated lymphoma cells show high level expression of CD95 on their cell surface, they are resistant to CD95-mediated apoptosis and T cell killing. Our recent study showed that CD95-mediated nonapoptotic signaling inhibits EBV lytic reactivation on these resistant lymphoma cell lines, which helps EBV to evade the host immune surveillance and facilitate associated lymphoma cell growth. There are two types of CD95 ligand physiologically, cleaved CD95 ligand (C-CD95L) and membrane-bound CD95 ligand (mCD95L). Our current study aims to define the specific roles of CD95 signaling mediated by C-CD95L and mCD95L in EBV-associated lymphomagenesis, which could help us to understand the specific response of different types of EBV-associated lymphomas and develop new specific immunotherapy.