Role of B7.2-mediated costimulation in Tcell homeostasis

免疫系统受到严格控制，以获得对一系列外来病原体的防御，并防止免疫媒介对我们自己的细胞造成损害。由于它们在调节免疫反应中的作用，人们对识别淋巴细胞上表达的促进其激活、失活或消除所必需的受体及其配体非常感兴趣。介导淋巴细胞活化的最重要的受体-配体对之一是CD28和B7.2，CD28表达在T淋巴细胞上，B7.2表达在特异性抗原提呈细胞上。受体CTLA-4也与B7.2结合，但它是T淋巴细胞功能的负调节因子。为了更好地了解B7.2对免疫反应的影响，我们在小鼠体内插入了一个允许该分子永久表达的基因。我们发现，B7.2表达的改变对两个T淋巴细胞亚群的动态平衡和分化有深刻而不同的影响，表明这些分子在调节T淋巴细胞的发育和动态平衡方面发挥着重要作用。我建议进行一项详细的研究，以便阐明这些分子控制免疫系统这一重要功能的机制。这些研究对于了解T淋巴细胞在体内的调节具有重要意义。

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.