Recent experience with the hantaviruses and with drug-resistant tuberculosis has emphasized our vulnerability to respiratory pathogens. We forget that the greatest virus pandemic in this century was caused any an influenza A virus, and that these viruses kill substantial numbers of people each year. Immunity is our only protection: no amount of behavioral modification can prevent the spread of a highly infectious respiratory virus within urban populations. Despite this, the few vaccines that are available are sub-optimal, reflecting our basic lack of understanding of how best to promote an effective immune response at the respiratory mucosa. This proposal continues the systematic, quantitative dissection of the cellular events in the lung and lymphoid tissue of mice infected with influenza A viruses. Substantial, novel information has emerged in the previous funding period. This rigorously developed in vivo model is proving of great value for showing subtle, but important, effects in (for instance) genetically disrupted """"""""knock-out"""""""" mice. The on-going experiments concentrate on the further definition of the response characteristics and effector mechanisms used by virus-specific CD4+ and CD8+ alpha beta T cell receptor (TCR)+ lymphocytes, the fate of these T cells and the roles of various cytokines. The analysis will inevitably provide further insights into the nature of cell-mediated immunity in general, the characteristics of virus clearance and pathology associated with this immune response, and suggest ways that immunity might be enhanced by manipulating normal host resistance mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI029579-09
Application #
2672001
Study Section
Experimental Virology Study Section (EVR)
Project Start
1990-04-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
9
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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Jenkins, Misty Rayna; Webby, Richard; Doherty, Peter C et al. (2006) Addition of a prominent epitope affects influenza A virus-specific CD8+ T cell immunodominance hierarchies when antigen is limiting. J Immunol 177:2917-25
Kedzierska, Katherine; Venturi, Vanessa; Field, Kenneth et al. (2006) Early establishment of diverse T cell receptor profiles for influenza-specific CD8(+)CD62L(hi) memory T cells. Proc Natl Acad Sci U S A 103:9184-9
Kedzierska, Katherine; La Gruta, Nicole L; Turner, Stephen J et al. (2006) Establishment and recall of CD8+ T-cell memory in a model of localized transient infection. Immunol Rev 211:133-45

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