CD8+ T-cells play a crucial role in eradicating viral infections. The focus of this project is two-fold. First, to study general in vivo mechanisms of virus - host interactions and second, to understand how primary and memory T-cells respond to virus infection. Despite the importance of T-cells, we do not yet fully understand the induction of a CD8+ T-cell responses and the generation of CD8+ T-cell memory to virus infection. For viruses in which traditional vaccine approaches have not been successful, it is hoped that induction of CD8+ T-cell memory will enhance immunity. To induce optimal CD8+ T-cell responses to vaccines it is necessary to understand how primary CD8+ T-cells are stimulated. This project aims to address questions related to the optimal and activation of T cell immunity following primary and secondary virus infection by studying several viruses and different routes of infection. This year our studies examining a poxvirus skin infection have demonstrated distinct roles for innate and adaptive immune cells in virus clearance.

Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2013
Total Cost
$748,434
Indirect Cost
City
State
Country
Zip Code
Filardy, A A; He, J; Bennink, J et al. (2016) Posttranscriptional control of NLRP3 inflammasome activation in colonic macrophages. Mucosal Immunol 9:850-8
Cush, Stephanie S; Reynoso, Glennys V; Kamenyeva, Olena et al. (2016) Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread. PLoS Pathog 12:e1005493
Yang, Ning; Gibbs, James S; Hickman, Heather D et al. (2016) Defining Viral Defective Ribosomal Products: Standard and Alternative Translation Initiation Events Generate a Common Peptide from Influenza A Virus M2 and M1 mRNAs. J Immunol 196:3608-17
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Yu, Cheng-Rong; Dambuza, Ivy M; Lee, Yong-Jun et al. (2013) STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis. Mediators Inflamm 2013:359674
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Gilchuk, Pavlo; Spencer, Charles T; Conant, Stephanie B et al. (2013) Discovering naturally processed antigenic determinants that confer protective T cell immunity. J Clin Invest 123:1976-87
Hickman, Heather D; Reynoso, Glennys V; Ngudiankama, Barbara F et al. (2013) Anatomically restricted synergistic antiviral activities of innate and adaptive immune cells in the skin. Cell Host Microbe 13:155-68

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