Impact of age and sex on human CD8 T cell activation and functions

年龄和性别对人类 CD8 T 细胞激活和功能的影响

• 批准号: RGPIN-2019-04976
• 负责人: Arbour, Nathalie
• 金额: $ 2.33万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761461
• 关键词: Impact; age; sex; human; CD8

Our immune system is composed of numerous cells and molecules that are patrolling from our blood stream to all organs. When a danger is detected in one organ these cells and molecules enter the targeted organ and start a whole cascade of events to get rid of the danger: be a potential tumor or a microbe. Amongst the white blood cells circulating in human blood, a particular cell type named CD8 T cell plays a key role in controlling microbes and abnormal cells. Following the first encounter with a threat they can recognize, CD8 T cells multiply, acquire multiple functions and then migrate into organs to find and efficiently eliminate the threat (microbes or abnormal cells). A proportion of these activated CD8 T cells remains in our body even after the threat (microbe or abnormal cell) is destroyed and stays as memory cells for extended periods of time. Accumulating evidence supports that sex and age influence CD8 T cells. Unfortunately, the factors causing such differences in women vs. men or young vs. older individuals are still incompletely understood. Notably, CD8 T cells from women can multiply more efficiently than cells from men. CD8 T cells from women exhibit greater capacity to destroy infected or abnormal cells. The differences between women and men could in part be due to sex hormones. However, CD8 T cells from post-menopause women (who have lower female sex hormones) are still more efficient than those from men of the same age. Therefore, other factors are potentially involved in these differences. The immune system becomes less efficient in older individuals compared to young adults. For example, vaccination aiming at boosting CD8 T cells to control infections such as influenza, is less efficient in older people than in young adults. As they age, individuals are exposed to multiple infections and consequently the proportion of their CD8 T cells that have been previously activated increases. The proposed research program deals with human CD8 T cells and aims to identify factors that contribute to the differences between men and women and/or between young and older adults. The factors that will be studied include soluble molecules (free-floating molecules), molecules on the surface of CD8 T cells as well as signals occurring inside these cells. In order to complete these studies various methods will be exploited from tissue culture, molecular biology and flow cytometry. Graduate students participating to this program will gain a diversified training in basic immunology, biology and complex data analysis. The final goal is to elucidate the molecular mechanisms involved in shaping CD8 T cell functions in healthy women and men across their lifespan.

我们的免疫系统是由无数的细胞和分子组成的，它们从我们的血液流向所有的器官。当在一个器官中检测到危险时，这些细胞和分子进入目标器官，开始一系列的事件来摆脱危险：成为潜在的肿瘤或微生物。在人类血液循环的白细胞中，一种名为CD8 T细胞的特殊细胞类型在控制微生物和异常细胞方面起着关键作用。在第一次遇到它们可以识别的威胁后，CD8 T细胞繁殖，获得多种功能，然后迁移到器官中以发现并有效消除威胁（微生物或异常细胞）。即使在威胁（微生物或异常细胞）被摧毁后，这些活化的CD8 T细胞中的一部分仍留在我们体内，并作为记忆细胞长时间停留。越来越多的证据支持性别和年龄影响CD8 T细胞。不幸的是，造成男女之间或年轻人与老年人之间这种差异的因素仍然不完全清楚。值得注意的是，来自女性的CD8 T细胞比来自男性的细胞繁殖效率更高。来自女性的CD8 T细胞表现出更强的破坏感染细胞或异常细胞的能力。女性和男性之间的差异可能部分是由于性激素。然而，来自绝经后女性（她们的女性性激素较低）的CD8 T细胞仍然比来自同龄男性的CD8 T细胞效率更高。因此，这些差异可能涉及其他因素。与年轻人相比，老年人的免疫系统效率较低。例如，旨在增强CD8 T细胞以控制流感等感染的疫苗接种在老年人中的效率低于年轻人。随着年龄的增长，个体暴露于多种感染，因此他们先前被激活的CD8 T细胞的比例增加。拟议的研究项目涉及人类CD8 T细胞，旨在确定导致男性和女性以及/或年轻人和老年人之间差异的因素。将被研究的因素包括可溶性分子（自由漂浮分子）、CD8 T细胞表面的分子以及这些细胞内发生的信号。为了完成这些研究，将利用组织培养、分子生物学和流式细胞术等多种方法。参加本项目的研究生将在基础免疫学、生物学和复杂数据分析方面获得多样化的训练。最终目标是阐明健康女性和男性一生中形成CD8 T细胞功能的分子机制。