AGE-RELATED CHANGES IN PRIMATE DENDRITIC CELL FUNCTION

比较健康的老年人对传染病的易感性 年轻人，这反映了免疫系统的衰老。树突状细胞(DC)是 先天免疫系统和获得性免疫系统的关键要素。我们假设华盛顿特区 功能可以在老的时候改变，从而有助于相对的 在这一人群中观察到的免疫受损状态。猕猴(Macaca) Mulatta)为解决这一假说提供了一个有价值的模型，因为存在 进行详细的免疫学分析，恒河猴提供了可重现的 与衰老的免疫系统密切相关的模型。我们建议评估与年龄相关的 不同年龄段DC变化的横断面和纵向比较 成群的猕猴。具体目标是： 1)通过测量来评估老化对DC功能的影响： (1)外围设备中前体DC(pDC1和IPC/pDC2)的数量和功能 血； (Ii)单核细胞来源的幼稚细胞表面分子和细胞因子的表达 从外周血分离的DC(IDC)和成熟DC(MDC)；以及 (Iii)前体DC和单核细胞来源的IDC和MDC的基因表达模式 采用基因芯片技术进行分析，并利用生物信息学方法进行分析。 2)体内外评价衰老对DC抗原摄取和迁移的影响。 3)体外观察衰老对DC抗原加工和提呈功能的影响 (单核细胞来源的树突状细胞的抗原提呈试验)；以及体内抗原启动 (评估引流淋巴结DC的体外APC功能)。这些研究将提供 洞察DC在免疫衰老中的作用，这反过来可能被用来改善 疫苗接种结果和老年人的健康。

Healthy elderly individuals demonstrate vulnerability to infectious diseases compared with young adults, which reflects senescence of the immune system. Dendritic cells (DC) are critical elements of both the innate and adaptive immune system. We hypothesize that DC function may be altered in the old so as to contribute to the relatively immunocompromised state observed in this population. The Rhesus macaque (Macaca mulatta) provides a valuable model for addressing this hypothesis because reagents exist for performing detailed immunological analysis and the Rhesus monkey provides a reproducible and closely parallel model of the aging immune system. We propose to assess age-related changes in DC by cross-sectional, as well as longitudinal, comparison between different age groups of macaques. The specific aims are: 1) To evaluate the effect of aging on DC function by measuring: (i) numbers and function of precursor DC (pDC1 and IPC/pDC2) in the peripheral blood; (ii) cell surface molecule and cytokine expression of monocyte-derived immature DC (iDC) and mature DC (mDC) isolated from the peripheral blood; and (iii) gene expression pattern of precursor DC and monocyte-derived iDC and mDC using cDNA microarray analysis, and analyzed using bioinformatics. 2) To evaluate the effect of aging on DC antigen uptake and migration, in vitro and in vivo. 3) To evaluate the effect of aging on DC antigen processing and presentation function in vitro (antigen presentation assays of monocyte-derived DC); and following antigen priming in vivo (evaluation of draining lymph node DC for ex vivo APC function). These studies will provide insight into the role of DC in immune senescence that in turn may be used to improve vaccination outcomes and the health of the elderly.