Role of B7.2-mediated costimulation in Tcell homeostasis

B7.2 介导的共刺激在 T 细胞稳态中的作用

• 批准号: 217506-2007
• 负责人: Fournier, Sylvie
• 金额: $ 2.19万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=424938
• 关键词: Role; B7.2; mediated; costimulation; Tcell

The immune system is tightly controlled to acheive the defense against an array of foreign pathogens and to prevent immune-mediated damage to our own cells. Because of their role in regulating immune responses, there has been a considerable interest in the identification of receptors and their ligands that are expressed on lymphocytes and which are necessary to promote their activation, inactivation or elimination. One of the most important receptor-ligand pairs mediating the activation of lymphocytes is CD28 which is expressed on T lymphocytes and B7.2 which is found on cells specialized in the presentation of antigen. The receptor CTLA-4 also binds B7.2, but is a negative regulator of T lymphocyte functions. In order to gain a better understanding of the influence of B7.2 on immune responses, we inserted a gene in mice that allows permanent expression of this molecule. We found that alterations of B7.2 expression have profound and differential effects on the homeostasis and differentiation of the two subsets of T lymphocytes, indicating a substantial role for these molecules in regulating the development and homeostasis of T lymphocytes. I propose a detailed study which should allow the elucidation of the mechanisms by which these molecules control this important function of the immune system. These studies have important implications for understanding the regulation of T lymphocytes in vivo.

免疫系统受到严格控制，以实现对一系列外来病原体的防御，并防止免疫介导的对我们自己细胞的损害。由于它们在调节免疫应答中的作用，在鉴定淋巴细胞上表达的受体及其配体方面存在相当大的兴趣，并且所述受体及其配体是促进其活化、失活或消除所必需的。介导淋巴细胞活化的最重要的受体-配体对之一是在T淋巴细胞上表达的CD 28和在专门呈递抗原的细胞上发现的B7.2。 受体CTLA-4也结合B7.2，但是是T淋巴细胞功能的负调节剂。 为了更好地了解B7.2对免疫反应的影响，我们在小鼠中插入了一个基因，允许该分子永久表达。 我们发现B7.2表达的改变对T淋巴细胞的两个亚群的稳态和分化具有深刻和不同的影响，表明这些分子在调节T淋巴细胞的发育和稳态中起着重要作用。 我建议进行一项详细的研究，以阐明这些分子控制免疫系统这一重要功能的机制。这些研究对于理解体内T淋巴细胞的调节具有重要意义。