The elderly are challenged with a number of risk factors that predispose them to severe respiratory tract infections. Principal among these is the inability to generate protective immunity following vaccination against influenza. This is due, in part, to decreased function of the naive CD4+ T cell compartment. This proposal outlines experiments designed to ask whether vaccines that incorporate CpG, and other toll-like receptor (TLR) ligands, can be used to meaningfully boost the aged naive CD4+ T cell response. This will be determined based upon whether vaccinating with antigen plus CpG restores both the aged naive CD4+ T cell effector response (Aim 1) and the development of subsequent memory (Aim 2). In order to directly compare the young and aged naive CD4+ T cell response we will remove this population from both young and aged D4+ T cell transgenic donors and adoptively transfer these cells to normal young recipients. These mice will then be immunized with the cognate antigen with or without CpG and the transgenic response can be followed using a congenic marker. Most importantly, by infecting with a recombinant influenza virus that expresses the cognate transgenic antigen we can assess the ability of young and aged effector or memory CD4+ T cells to protect from viral infection following vaccination with or without CpG. Lastly, to determine the feasibility of this approach in aged recipients we will ask whether aged dendritic cells are activated by CpG, and other TLR ligands, to enhance antigen specific naive CD4+ T cell responses (AIM 3). ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AG027641-01
Application #
7052631
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Fuldner, Rebecca A
Project Start
2006-01-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
1
Fiscal Year
2006
Total Cost
$48,296
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
020658969
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983
Jones, Stephen C; Brahmakshatriya, Vinayak; Huston, Gail et al. (2010) TLR-activated dendritic cells enhance the response of aged naive CD4 T cells via an IL-6-dependent mechanism. J Immunol 185:6783-94
Jones, Stephen C; Clise-Dwyer, Karen; Huston, Gail et al. (2008) Impact of post-thymic cellular longevity on the development of age-associated CD4+ T cell defects. J Immunol 180:4465-75