Respiratory virus infections ar a major problem for the aged, the very young, and a common complicating factor in immunocompromised transplant or cancer patients. In this context, the practical challenges are to develop better vaccines and enhanced mechanisms for maintaining and manipulating the cell populations that comprise immunological memory. The obverse of this problem is the desire to subvert the consequences of prior antigen priming in, for example, the use of virus-vector systems for gene therapy of cystic fibrosis. An underlying difficulty for both sets of approaches is that immunological memory is, in general, poorly understood. The experimental dissection of memory is technically demanding, rigorous analytical approaches have often been lacking, and there is substantial controversy and confusion. Many of the studies with non-viral systems are of limited value, as the experiments have been done with phenotypically- marked lymphocyte populations of unknown antigen specificity. Considerable effort has thus been made to develop mouse models for the quantitative, functional analysis of T cell memory to a parainfluenza type 1 virus (Sendai) and to the influenza A viruses. The intention is to use these experimental systems for the further clarification of the establishment, maintenance and recall phase of virus-specific CD4+ and CD8+ T cell memory. Attention will be given to the relative significance of events driven via the clonotypic T cell receptor for antigen, and the possible consequences of both intercurrent infections and more physiologically-mediated processes associated with the maintenance of homeostasis in the total pool of T lymphocytes. The experiments will inevitably lead to better understanding of the nature of T cell memory, and help provide novel insights for both vaccine development and possible therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038359-03
Application #
2672550
Study Section
Virology Study Section (VR)
Project Start
1996-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
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