Dendritic Cells in the Aged

描述（由申请人提供）：我们发现在老年宿主中产生的T细胞应答由于老年微环境而减少。具体地说，我们发现，老年小鼠的树突状细胞（DC）不能有效地刺激或招募到引流的次级淋巴器官。此外，老年人减少的T细胞反应可以通过从年轻小鼠转移DC而部分恢复，但从老年小鼠转移DC则较少，这表明老年人中存在DC缺陷。我们的中心假设是，老年人T细胞应答的下降/改变也是成熟免疫原性DC的次优生成以及DC与T细胞之间有限相互作用的结果。我们将确定：1.）DC数量和/或子集表示是否随老化而改变; 2.）如果免疫DC的老化微环境不利于DC的最佳活化/成熟;和3.）老年人的DC诱导T细胞应答的能力是否降低，但它们诱导耐受的能力是否保持完整。从这些研究中获得的信息将有助于设计优化老年人免疫接种的策略。

DESCRIPTION (provided by applicant): We found that T cell responses generated in an aged host are diminished as a consequence of the aged microenvironment. Specifically, we found that dendritic cells (DCs) in aged mice are not efficiently stimulated or recruited to the draining secondary lymphoid organ. Furthermore, the diminished T cell response in the aged can be partially restored by the transfer of DCs from young mice but less with DCs from old mice, suggesting a DC defect in the aged. Our central hypothesis is that the decline/alteration in T cell responses in the aged is also a consequence of suboptimal generation of mature, immunogenic DCs and the limited interaction between DCs and T cells. We will determine: 1.) whether DC number and/or subset representation is altered with aging; 2.) if the aged microenvironment in which DCs are immunized is not conducive for optimal activation/maturation of DCs; and 3.) whether DCs of the aged have a diminished capacity to induce T cell responses but their ability to induce tolerance remains intact. The information gained from these studies will aid in designing strategies for optimizing immunization in the aged.