膜结合的CD95连接体调节CD19介导的B细胞受体信号传递和EBV激活
Mu Liu1, Chenxu Huang1, Xingchen Zhou1
1Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Journal of medical virology
|February 1, 2024
概括
更多表达CD95连接体 (CD95L) 的工程T细胞有效地杀死移植受体中的爱斯坦-巴尔病毒 (EBV) 感染细胞. 这种方法增强了移植后淋巴增殖性疾病 (PTLD) 的T细胞免疫疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 在瘤学瘤学.
背景情况:
- 移植后淋巴增殖性疾病 (PTLD) 与移植受体中的爱斯坦-巴尔病毒 (EBV) 有关.
- 来自EBV感染的淋巴状细胞系 (LCL) 通常容易受到CD95介导的亡和细胞毒性T淋巴细胞 (CTL) 活性的影响.
研究的目的:
- 研究CD95连接体 (CD95L) 形式在PTLD发病过程中的作用,并探索治疗潜力.
- 为了评估工程EBV特异性CTL与增强的CD95L表达的PTLD治疗的疗效.
主要方法:
- 使用的CD95L的复合性跨膜 (mCD95L) 和可溶性 (sCD95L) 形式.
- 评估了CD95L对LCL亡,CD19信号传递和EBV激活的影响.
- 设计了EBV特定的CTL来过度表达mCD95L,并测试了它们的杀死活性.
主要成果:
- 可溶性CD95L对LCL没有影响,而mCD95L诱导了CD19降解,损害了B细胞受体 (BCR) 信号和EBV激活.
- 卡斯巴酶抑制恢复了CD19的表达,但没有恢复EBV的Lytic基因表达.
- 过度表达mCD95L的工程CTLs证明了对LCLs的增强杀伤.
结论:
- mCD95L介导的CD19降解是控制EBV感染B细胞的关键机制.
- 为了过度表达mCD95L,工程EBV特定的CTLs为PTLD免疫治疗提供了一个有前途的策略.
相关概念视频
B Cell Activation and Differentiation
1.7K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.7K
T Cell Activation and Clonal Selection
735
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
735
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
Diversity of Antigen Receptors
589
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
589
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K


