期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 12, 页码 8215-8225出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.12.8215
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资金
- The Damon Runyon Foundation
- The Dana Foundation
- United States Public Health Service [K08 DA11880, U19 AI040035, R01 DA024565]
Hepatitis C virus (HCV) is an Important human pathogen that represents a model for chronic infection given that the majority of infected individuals fall to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. Although viral sequence evolution at targeted MHC class I-restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. To explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from subjects who progress to chronic HCV infection than from those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV-specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection. The Journal of Immunology, 2008, 181: 8215-8225.
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