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 #
5R01AI038359-05
Application #
6169279
Study Section
Virology Study Section (VR)
Program Officer
Lambert, Linda C
Project Start
1996-04-01
Project End
2001-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
5
Fiscal Year
2000
Total Cost
$182,819
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Belz, Gabrielle T; Liu, Haiyan; Andreansky, Samita et al. (2003) Absence of a functional defect in CD8+ T cells during primary murine gammaherpesvirus-68 infection of I-A(b-/-) mice. J Gen Virol 84:337-41
Belz, G T; Xie, W; Doherty, P C (2001) Diversity of epitope and cytokine profiles for primary and secondary influenza a virus-specific CD8+ T cell responses. J Immunol 166:4627-33
Flano, E; Woodland, D L; Blackman, M A et al. (2001) Analysis of virus-specific CD4(+) t cells during long-term gammaherpesvirus infection. J Virol 75:7744-8
Turner, S J; Cross, R; Xie, W et al. (2001) Concurrent naive and memory CD8(+) T cell responses to an influenza A virus. J Immunol 167:2753-8
Belz, G T; Doherty, P C (2001) Virus-specific and bystander CD8+ T-cell proliferation in the acute and persistent phases of a gammaherpesvirus infection. J Virol 75:4435-8
Topham, D J; Castrucci, M R; Wingo, F S et al. (2001) The role of antigen in the localization of naive, acutely activated, and memory CD8(+) T cells to the lung during influenza pneumonia. J Immunol 167:6983-90
Christensen, J P; Doherty, P C; Branum, K C et al. (2000) Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory. J Virol 74:11690-6
Riberdy, J M; Christensen, J P; Branum, K et al. (2000) Diminished primary and secondary influenza virus-specific CD8(+) T-cell responses in CD4-depleted Ig(-/-) mice. J Virol 74:9762-5
Sangster, M Y; Topham, D J; D'Costa, S et al. (2000) Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. J Immunol 164:1820-8
Stevenson, P G; Efstathiou, S; Doherty, P C et al. (2000) Inhibition of MHC class I-restricted antigen presentation by gamma 2-herpesviruses. Proc Natl Acad Sci U S A 97:8455-60

Showing the most recent 10 out of 28 publications