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.
|Linton, Phyllis-Jean; Thoman, Marilyn L (2014) Immunosenescence in monocytes, macrophages, and dendritic cells: lessons learned from the lung and heart. Immunol Lett 162:290-7|
|Kovacs, Elizabeth J; Palmer, Jessica L; Fortin, Carl F et al. (2009) Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol 30:319-24|