催生酶CD38调节CD4T细胞的免疫代谢反应,并参与HIV的发病过程
Fernando Díaz-Basilio1,2, Moisés Vergara-Mendoza3, Jessica Romero-Rodríguez4
1Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosío Villegas, Calzada de Tlalpan 4502, Tlalpan, 14080 Mexico City, Mexico.
Journal of leukocyte biology
|March 11, 2024
概括
通过限制代谢变化,CD38s酶活性限制了HIV中CD4 T细胞的反应. 抑制CD38恢复T细胞功能和新陈代谢,为HIV免疫病原发生提供了潜在的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢调节 代谢调节 代谢调节
- 艾滋病病毒的发病因子
背景情况:
- CD38表达与艾滋病毒感染相关,但其在CD4 T细胞免疫代谢中的确切作用尚不清楚.
- 了解CD38的功能对于解决HIV的T细胞功能障碍至关重要.
研究的目的:
- 调查CD38的ectoenzyme活动在调节CD4 T细胞代谢和功能的作用.
- 确定抑制CD38是否可以恢复HIV感染个体的T细胞反应.
主要方法:
- 使用了来自HIV+患者的Jurkat T CD4细胞和原发性T细胞.
- 评估了代谢参数 (OCR/ECAR比率,糖解,线粒体功能) 和T细胞反应 (增殖,细胞因子产生,分化).
- 使用药理抑制CD38的催化活性.
主要成果:
- CD38的糖酶活性限制了对T细胞受体 (TCR) 刺激的代谢重编程和功能反应.
- 消除CD38的ectoenzyme功能可以增强TCR诱导的循环,增殖,生存和CD40L诱导.
- 在HIV+患者的T细胞中对ecto-CD38的药理抑制恢复了TCR反应,使糖分解正常化,并改善了线粒体功能.
结论:
- 乙酶CD38在TCR驱动的T细胞激活上起到免疫代谢制动作用.
- 艾滋病毒中CD38过度表达有助于CD4 T细胞功能障碍.
- 向CD38的催化活性可能是改善HIVT细胞免疫力的治疗策略.
相关概念视频
T Cell Activation and Clonal Selection
731
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...
731
Cytotoxic T Cells-mediated Immune Response
908
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
908
T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
Cell-mediated Immune Responses
68.3K
Overview
68.3K


