AGE RELATED EFFECTS ON T LYMPHOCYTE ADHESION

衰老伴随着免疫功能的逐渐下降， 它同时影响免疫系统的体液和细胞分支 系统因此，老年人口成为 特别容易受到可能危及生命的感染 和癌症。识别正常人中与年龄相关的关键变化 因此，免疫系统细胞的功能变得重要。 阻止或逆转免疫力整体下降的步骤 反应T淋巴细胞和淋巴细胞之间的初始相互作用 抗原提呈细胞（APC）是一个关键的过程，在安装一个 免疫反应肽/II类MHC形式的抗原 复合物被克隆型T细胞受体（TCR）识别， 与CD 4辅助受体结合。此外，一些非- 抗原特异性或“辅助”T细胞分子与配体结合 在APC上表达，从而促进两者之间的粘附 细胞类型。在过去的几年里，许多T细胞的亲和力 辅助分子相互作用已被证明是急性 由TCR参与调节。因此，一旦抗原被识别， 通过TCR，辅助分子相互作用的强度是 迅速增加，作为直接后果，附件 分子参与T细胞活化的共信号传导。在 在本申请中，我们建议检查年龄相关的变化， TCR上调的粘附和T细胞整合素的共同信号传导 LFA-1（CD11a/CD18）、VLA-4（CD49d/CD29）、VLA-5（CD49e/CD29）和VLA-5（CD49e/CD29）。 玻连蛋白受体（CD 51/CD 61）。这些整合素中的每一种都发挥着 在年轻时成熟T细胞功能中的重要作用 动物;因此，获得的结果将提供有价值的 关于衰老如何影响T细胞初始相互作用的信息 他们的APC。

Aging is accompanied by a progressive decrease in immune function, which affects both the humoral and cellular arms of the immune system. As a consequence, the elderly population becomes particularly susceptible to potentially life-threatening infections and cancers. Identifying key age-associated changes in the normal functioning of cells of the immune system thus becomes an important step in arresting or reversing the overall decline in the immune response. The initial interaction between a T lymphocyte and an antigen-presenting cell (APC) is a pivotal process in mounting an immune response. Antigen in the form of peptide/class Il MHC complexes is recognized by the clonotypic T cell receptor (TCR), in conjunction with the CD4 coreceptor. In addition, several non- antigen-specific or 'accessory' T cell molecules bind to ligands expressed on the APC, and thus facilitate adhesion between the two cell types. Over the last several years, the avidity of many T cell accessory molecule interactions has been shown to be acutely regulated by TCR engagement. Thus, once antigen has been recognized by the TCR, the strength of the accessory molecule interactions are rapidly increased, and as a direct consequence the accessory molecule participates in cosignaling for T cell activation. In the present application, we propose to examine age-related changes in TCR-upregulated adhesion and cosignaling by the T cell integrins LFA-1 (CDlla/CD18), VLA-4 (CD49d/CD29), VLA-5 (CD49e/CD29) and the vitronectin receptor (CD51 /CD61). Each of these integrins play important roles in the function of mature T cells from young animals; the results obtained will therefore provide valuable information on how aging influences the initial interaction T cells and their APC.