CD8 T 细胞为结肠中的新抗原+上皮干细胞进行免疫监测
Jessica Buck1, Nivedita R Iyer1, Eric Fagerberg1
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
CD8 T细胞可以早期检测和消除具有新突变 (新抗原) 的结肠上皮细胞. 这种免疫监测通过向新抗原+干细胞而防止癌症,而不会引起炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 癌症研究 癌症研究
背景情况:
- 结直肠上皮细胞积累了体质突变,其中一些形成了新抗原.
- 结肠中CD8T细胞免疫监测对于早期癌症检测至关重要,但可能面临耐受性挑战.
研究的目的:
- 为了调查新抗原特异性CD8 T细胞是否可以在不诱导耐受性的情况下在结肠中进行免疫监测.
- 了解CD8 T细胞介导的结肠中新抗原表达细胞的清除机制.
主要方法:
- 利用一种基因工程小鼠模型,在结肠上皮细胞中表达一种新抗原.
- 采用了免疫光和单细胞转录组分析.
- 在包括炎症和衰老在内的各种条件下,在结肠上皮细胞中检查PD-L1表达.
主要成果:
- 新抗原表达触发了新抗原+上皮细胞 (包括干细胞) 的 CD8 T 细胞依赖性消除.
- 新抗原特异性CD8 T细胞在结肠内获得了效应器功能,尽管PD-1表达.
- 令人惊的是,结肠上皮细胞和干细胞缺乏PD-L1表达,即使是在炎症条件下或IFN-γ刺激下.
结论:
- 新抗原的获取启动了结肠中CD8 T细胞介导的免疫监测.
- 通过 CD8 T 细胞消除 PD-L1 阴性新抗原+ 干细胞,加上新抗原阴性细胞的修复,可以预防癌症和免疫病理.
- PD-L1基因促进体的高甲基化可能导致其在结肠上皮细胞中的低表达.
相关概念视频
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
01:23Renewal of Intestinal Stem Cells
3.1K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.1K
02:40Cancer Stem Cells and Tumor Maintenance
5.8K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
01:22T Cell Activation and Clonal Selection
14.6K
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...
14.6K
01:27Cytotoxic T Cells-mediated Immune Response
6.4K
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...
6.4K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K