铁亡会加剧病毒特异性耗尽的CD8+ T细胞的克隆删除
Qin Tian1, Cheng Chen2, Jinjin Lu2
1Dermatology Hospital, Southern Medical University, Guangzhou, China.
Frontiers in immunology
|December 10, 2024
概括
铁亡是一种细胞死亡形式,在慢性感染期间导致CD8+ T细胞 (TEX) 耗尽的损失. 抑制铁灭能保护这些重要的TEX细胞,从而更好地清除病毒和消除瘤.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 在慢性感染和癌症期间,持续的抗原刺激会导致CD8+T细胞耗尽 (TEX).
- TEX细胞保留了对病原体清除和瘤抑制至关重要的效应因子功能.
- 对于TEX细胞克隆性缺失的机制的了解很少,与研究TEX细胞再生相反.
研究的目的:
- 为了研究铁灭菌在病毒特异性TEX细胞的克隆删除中的作用.
- 探索脂质过氧化,氧化应激和T细胞存活之间的联系.
主要方法:
- 使用了淋巴细胞胆膜炎病毒 (LCMV) 感染的小鼠模型.
- 评估了谷氨过氧化酶4 (GPX4) 活性和铁灭抑制对TEX细胞群的影响.
- 在TEX细胞中量化了脂质过氧化和氧化应激标志物.
主要成果:
- 过度的脂质过氧化诱导了病毒特异性TEX细胞中的铁亡,与线粒体氧化应激相关,并降低了GPX4活性.
- GPX4缺乏症加剧了铁亡,并减少了TEX细胞数量.
- 铁酶抑制或GPX4过度表达拯救了TEX细胞免于枯竭.
结论:
- 铁亡是驱动病毒特异性TEX细胞的克隆删除的一个关键机制.
- 向铁亡是一种有希望的策略,可以增强TEX细胞的持久性,以改善免疫疗法和感染控制.
相关概念视频
T Cell Activation and Clonal Selection
658
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...
658
Cytotoxic T Cells-mediated Immune Response
846
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...
846
Immune Response Against Viral Pathogens
748
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
748
Necrosis
4.3K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.3K
Tumor Immunotherapy
476
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
476
Immunodeficiency Diseases
903
Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
There are three main causes of immunodeficiency...
903


