The role of HOX 4 paralog genes in maintenance and expansion of T memory cells

HOX 4旁系同源基因在T记忆细胞维持和扩增中的作用

• 批准号: 342301-2011
• 负责人: Bijl, Janetta
• 金额: $ 2.19万
• 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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=549618
• 关键词: role; HOX; paralog; genes; maintenance

Our immune cells patrol the body to detect and respond to external invaders, such as bacteria's and viruses. Once they have cleared the attack, a few immune cells will be kept for years, enabling us to act more efficiently in second attack of the same intruder. We refer to these cells as immunological memory. There are two classes of memory cells, those of the B-cell type (predominantly involved in bacterial infections) and of the T-cell type (predominantly involved in viral infections). The number of memory cells is very low, and to prevent their loss, due to maturation into effector immune cells upon repeated encounter with the intruder, these cells divide occasionally into two daughter cells of which at least one is exactly the same as the original cell. Blood stem cells, which are even rarer, undergo as well this type of self-renewal divisions to maintain their numbers, enabling to provide a life-time blood supply. The current thought is that molecules determining the self-renewal divisions are the same in both cell types. We are interested in understanding how to expand the T memory cell pool. The protein Hoxb4 is known to increase the blood stem cell numbers, and thus we hypothesized that this protein can expand memory cells as well. Our first results show indeed a better expansion of a T memory cell subset in the presence of Hoxb4 than control. Using mice we want to test whether these expanded memory cells can produce an immune response. Furthermore, other memory cell subsets will be tested for expansion with Hoxb4 in cell culture and in a mouse. Finally, we will investigate the relation between Hox genes and other molecules (Wnt) that have recently been shown to be important in memory T cells.

我们的免疫细胞在体内巡逻，探测并应对外部入侵者，如细菌和病毒。一旦它们清除了攻击，一些免疫细胞将被保留数年，使我们能够更有效地应对同一入侵者的第二次攻击。我们把这些细胞称为免疫记忆。有两类记忆细胞，一类是b细胞型（主要参与细菌感染），另一类是t细胞型（主要参与病毒感染）。记忆细胞的数量非常少，为了防止它们的丢失，由于在与入侵者反复接触后成熟为效应免疫细胞，这些细胞偶尔会分裂成两个子细胞，其中至少有一个与原始细胞完全相同。更为罕见的造血干细胞也经历了这种自我更新的分裂，以维持其数量，从而能够提供终生的血液供应。目前的想法是，决定自我更新分裂的分子在两种细胞类型中是相同的。我们感兴趣的是了解如何扩展T内存单元池。已知Hoxb4蛋白可以增加血液干细胞的数量，因此我们假设这种蛋白也可以增加记忆细胞。我们的第一个结果表明，在Hoxb4的存在下，T记忆细胞子集的扩展确实比对照组更好。我们想用老鼠来测试这些扩展的记忆细胞是否能产生免疫反应。此外，其他记忆细胞亚群将在细胞培养和小鼠中进行Hoxb4扩增测试。最后，我们将研究Hox基因和其他分子（Wnt）之间的关系，这些分子最近被证明在记忆T细胞中很重要。