Increased PD-L1 Expression and PD-L1/CD86 Ratio on Dendritic Cells Were Associated With Impaired Dendritic Cells Function in HCV Infection

Impaired hepatitis C virus (HCV)-specific T cell immunity was associated with the persistence of HCV infection. Dysfunction of dentritic cells (DCs) was believed to be involved in T cell exhaustion, but the mechanisms were rarely understood. In this study, surface costimulatory marker (CD83, CD86, and CD40), coinhibitory marker (PD-L1) expression and allostimulatory capacity of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were evaluated in HCV-infected patients. Results showed that the expression of both costimulatory and coinhibitory markers was increased in HCV-infected patients compared with healthy controls. PD-L1/CD86 ratio was increased and positively correlated with PD-L1 expression on DCs in HCV-infected patients. Allostimulatory capacity of DCs was impaired and inversely correlated with PD-L1 expression and PD-L1/CD86 ratio. These findings suggested that the effect of inhibitory marker PD-L1 overwhelmed the effect of costimulatory markers and down regulated DC-T activation in HCV-infected patients. The results will be helpful to understand the mechanism of dysfunction of DCs in HCV infection and shed light on the DC-based immunotherapeutic strategy. J. Med. Viral. 82:1152-1159, 2010. (C) 2010 Wiley-Liss, Inc.