Homeostasis of Mature T Cells in the Aged

老年人成熟 T 细胞的稳态

• 批准号: 6422551
• 负责人: Charles D. Surh
• 金额: $ 32.41万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6422551
• 关键词: T lymphocyte; age difference; aging; animal old age; antigens; autologous transplantation; bone marrow transplantation; cell population study; cell transplantation; cellular immunity; cytotoxic T lymphocyte; flow cytometry; gene expression; genetically modified animals; helper T lymphocyte; homeostasis; immature animal; immunologic memory; immunosenescence; interleukin 7; laboratory mouse; lymphocyte proliferation; lymphopoiesis; major histocompatibility complex; mature animal; organ culture

Aging is associated with a decline in the repertoire and the functional capacity of the mature T cells. The reduced ability of the aged cellular immune system to respond to new antigenic challenges appears to be largely a result of attrition in the size of the naive T cell pool and the decline in the responsiveness of the antigen-specific T cells. Exactly what causes the reduction of the naive T cell pool is not known, but is generally believed to be a combination of decreased thymic output of newly generated T cells coupled with life-long conversion of naive cells into memory cells from exposure to antigens. Other mechanisms, however, are possible, especially when one considers that T cells are subject to constant regulation by homeostatic mechanisms that regulate the overall size and the composition of the T cell pool. In this respect, we and others have recently begun to identify the essential factors that regulate the homeostasis of naive and memory T cells. To determine whether the decline in the naive cells in the aged is partly caused by age-related changes in the factors that control T cell homeostasis, we propose following three areas of investigation. First, the host environment of the aged will be tested for their capacity to support homeostasis of naive and memory T cells. Second, the expression of factors that regulate homeostasis of naive T cells will be measured in aged mice. Third, the possibility of restoring the naive T cell pool in old mice through manipulation of the homeostatic factors will be tested.

衰老与成熟 T 细胞的功能和功能下降有关。 衰老的细胞免疫系统应对新抗原挑战的能力下降似乎很大程度上是由于初始 T 细胞库大小的消耗和抗原特异性 T 细胞的反应性下降所致。 导致幼稚T细胞库减少的确切原因尚不清楚，但通常认为是新产生的T细胞胸腺输出减少，加上幼稚细胞因暴露于抗原而终生转变为记忆细胞的组合。 然而，其他机制也是可能的，特别是当人们认为 T 细胞受到调节 T 细胞池总体大小和组成的稳态机制的持续调节时。 在这方面，我们和其他人最近开始确定调节初始 T 细胞和记忆 T 细胞稳态的重要因素。 为了确定老年人幼稚细胞的下降是否部分是由控制 T 细胞稳态的因素与年龄相关的变化引起的，我们建议进行以下三个研究领域。 首先，将测试老年人的宿主环境支持幼稚 T 细胞和记忆 T 细胞稳态的能力。 其次，将在老年小鼠中测量调节初始 T 细胞稳态的因子的表达。第三，将测试通过操纵稳态因子来恢复年老小鼠中初始 T 细胞库的可能性。