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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
7R01AG026727-04
Application #
7893365
Study Section
Special Emphasis Panel (ZRG1-BDA-F (02))
Program Officer
Fuldner, Rebecca A
Project Start
2007-02-15
Project End
2012-01-31
Budget Start
2009-08-15
Budget End
2010-01-31
Support Year
4
Fiscal Year
2009
Total Cost
$337,487
Indirect Cost
Name
San Diego State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
073371346
City
San Diego
State
CA
Country
United States
Zip Code
92182
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