T Cell Maturation and Thymic Activity in the Aged

超出所提供的空间。衰老导致免疫系统的变化，包括记忆T细胞比例的急剧增加和相应的幼稚T细胞数量的减少，尽管T细胞的绝对数量没有变化。这种转变的最终结果可能反映在老年人患癌症和传染病的风险增加上。该项目的目标是通过控制T细胞的亚群分布来提高老年人的免疫反应性，并验证年龄相关的免疫活性改变是由功能不同的幼稚T细胞和记忆T细胞的代表性频率变化引起的假设。在刚刚过去的资助期内，研究人员将骨髓移植作为一种改变老年宿主体内记忆细胞和幼稚T细胞比例的方法。这些发现构成了这一时期有待检验的假设的基础；随着年龄的增长，从幼稚的T细胞群转变为记忆丰富的T细胞群，这是由于微环境的变化导致T淋巴细胞稳态的改变。三个具体目标将解决这一假设。首先，我们将确定影响T细胞稳态的微环境中与年龄相关的变化。其次，我们将确定T淋巴细胞的寿命，扩张和成熟如何响应微环境的老化。最后，我们将利用前两个目标中获得的信息来操纵微环境，以改善老年人的T细胞功能和整体免疫反应性。这些研究的目的是提高我们对衰老过程中T细胞功能的认识，最终目的是增强老年人的免疫反应性，并在化疗、骨髓移植或艾滋病抗病毒治疗后实现更好的免疫重建。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Aging results in well documented changes in the immune system, including a dramatic increase in the proportion of memory T cells and a corresponding decrease in the naive T cell population, although the absolute number of T cells does not change. The end result of this shift may be reflected in the increased risk of cancer and infectious disease in the elderly. The goal of this program has been to improve immunoreactivity in the aged by manipulating the subset distribution of T cells, and testing the hypothesis that age-related alterations in immunological activity result from this shift in representational frequency of the functionally distinct naive and memory T cells. The immediate past funding period looked at bone marrow transplantation as a way to alter the ratio of memory and naive T cells in the aged host. The findings form the basis for the hypothesis to be tested in this period; the shift from a naive to a memory-enriched T cell population associated with advancing age is due to altered T lymphocyte homeostasis resulting from changes in the microenvironment. Three specific aims will address this hypothesis. First we will identify the age-associated changes in the microenvironment that affect T cell homeostasis. Secondly, we will determine how T lymphocyte lifespan, expansion and maturation respond to aging of the microenvironment. Lastly, we will manipulate the microenvironment using the information gained in the first two aims, to improve T cell function and overall immune reactivity in the aged. The intent of these studies is to improve our knowledge of T cell function in aging, with the ultimate goal of strengthening immune reactivity in aged individuals and achieving better immunoreconstitution following chemotherapy, bone marrow transplantation, or antiviral treatment for AIDS. PERFORMANCE SITE ========================================Section End===========================================