This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Infection with hepatitis C virus (HCV) results in persistent liver disease in the majority of infected individuals and HCV-associated end-stage liver disease is now the leading indication for liver transplantation in the United States. Many studies have highlighted the importance of the T cell response for viral clearance and attributed persistent infection to an insufficient T cell response. However, in persistent HCV infection the factors leading to immune failure are not clear. We postulate that in the natural course of HCV infection, viral persistence is a direct result of the inadequacy of the intrahepatic immune response and more specifically, that intrahepatic antigen presenting cells (APCs) modulate and impair the antiviral T cell response thereby contributing to viral persistence. Hepatic stellate cells (HSC) are a novel population of intrahepatic APC that undergo dramatic phenotypic and functional changes in response to liver injury or infection. Our preliminary work indicates a transition from immunostimulatory to immunoinhibitory function upon activation of HSC. Work proposed here will focus on HSC and their ability to modulate T cell immunity through viral antigen presentation in the context of costimulatory or coinhibitory molecules and the influence that HCV has on this process. We will dissect the pair-wise relationships between HSC and T cells, HSC and HCV, while bringing together all three factors to determine the impact of this tripartite interaction on the outcome of HCV infection. We expect to find that HSC play a role in the intrahepatic T cell dysfunction during HCV infection, promoting persistent infection.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000165-51
Application #
8357563
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Project Start
2011-08-01
Project End
2012-04-30
Budget Start
2011-08-01
Budget End
2012-04-30
Support Year
51
Fiscal Year
2011
Total Cost
$32,906
Indirect Cost
Name
Emory University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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