Dendritic Cells in the Aged

老年人的树突状细胞

• 批准号: 7576723
• 负责人: Phyllis-Jean Linton
• 金额: $ 1.37万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576723
• 关键词: Affect; Age; Aging; Agonist; Allogenic; Antibody Formation; Antigen Presentation; Antigen Presentation Pathway; Antigens; Back; Biological; Bone Marrow; Cell Aging; Cell Count; Cell Maturation; Cell physiology; Cells; DEC-205 receptor; Data; Defect; Delayed Hypersensitivity; Dendritic Cells; Effector Cell; Generations; Goals; Hematopoietic stem cells; Immune system; Immunity; Immunization; In Vitro; Infection; Inflammation; Inflammatory; Lymphoid; Mediastinal lymph node group; Mediating; Mus; Organ; Output; Poly U; Process; Production; Recruitment Activity; Site; T-Lymphocyte; Testing; Thymus Gland; Up-Regulation; Virus; Virus Diseases; age related; aged; cell age; cytokine; cytotoxic; design; immunogenic; in vivo Model; influenzavirus; migration; response; senescence

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.

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。