亲炎性细胞维持T细胞大粒状淋巴细胞白血病中白血病的克隆扩张
Cristina Vicenzetto1, Vanessa Rebecca Gasparini1, Gregorio Barila1
1Department of Medicine, Hematology and Clinical Immunology Branch, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine (VIMM), Padova.
Haematologica
|July 13, 2023
概括
这项研究表明,T细胞大粒状淋巴细胞白血病 (T-LGLL) 的非白血病细胞表现出促炎活性,特别是在症状患者中. T-LGLL患者的单细胞显示异常激活,表明新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 在瘤学瘤学.
背景情况:
- T细胞大颗粒性淋巴细胞白血病 (T-LGLL) 是一种慢性淋巴增殖性疾病.
- 症状T-LGLL通常与CD8+STAT3突变有关,而惰的病例包括CD8+野生型,CD4+STAT5B突变和野生型变种.
- 非白血病细胞在T-LGLL病原发生中的作用尚不清楚.
研究的目的:
- 为了表征T-LGLL患者的炎症性非白血病细胞.
- 研究这些细胞在支持白血病T-LGLL生长中的作用.
- 为了确定症状和无症状T-LGLL患者之间非白血病细胞活性的差异.
主要方法:
- 流细胞计和免疫类型定型用于分析细胞群.
- 从单细胞中释放的细胞因子 (例如,互白素-6) 的分析.
- 对单细胞中信号通路激活的评估.
- 发现与临床T-LGLL亚型 (症状与无症状) 的相关性.
主要成果:
- 有症状的T-LGLL患者 (CD8+STAT3突变) 呈现出歪曲的Th17/Treg比率和中级/非经典单细胞的增加.
- 症状T-LGLL患者的单细胞在CCL5刺激后释放出高水平的互白素-6,CCL5是一种由白血病LGL产生的化学激素.
- 无症状的T-LGLL病例没有显示出单细胞分布的改变,但他们的单细胞显示出异常的信号通路激活.
- 在非白血病细胞中,根据T-LGLL临床表现,观察到明显的炎症前驱特征.
结论:
- 非白血病细胞群,特别是单细胞,在T-LGLL病原发生中发挥着重要作用.
- 单细胞激活和细胞因子产生在症状和无症状T-LGLL之间有所不同,突出显示了它们在疾病进展中的不同作用.
- 这些发现为开发针对T-LGLL中非白血病细胞的新疗法提供了理由.
相关概念视频
Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
T Cell Types and Functions
1.1K
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...
1.1K
Cells of the Adaptive Immune Response
1.0K
The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
1.0K
T Cell Activation and Clonal Selection
822
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...
822
Disorders of Leukocytes
984
Leukocyte disorders can lead to either leukopenia, characterized by an abnormally low leukocyte count, or leukocytosis, marked by a very high leukocyte number.
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune...
Leukopenia may result from bone marrow disorders, autoimmune diseases, and infectious diseases. For example, conditions such as multiple myeloma and aplastic anemia can impair the bone marrow's ability to produce adequate leukocytes. Similarly, autoimmune diseases like lupus and viral infections such as HIV can prompt the immune...
984
Cytotoxic T Cells-mediated Immune Response
985
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...
985


