Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: Effect of viremia levels and antiviral treatment.
J Hepatol. 2008 Jan 28
Urbani S, Amadei B, Tola D, Pedrazzi G, Sacchelli L, Cavallo MC, Orlandini A, Missale G, Ferrari C.
Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Italy.
BACKGROUND/AIMS:
HCV-specific T cells in acute hepatitis C with subsequent chronic evolution are dysfunctional and most of them express PD-1. The aim of the study was to investigate to what extent the antiviral T cell function can be restored by reversing T cell exhaustion by PD-1/PD-L1 blockade and to assess whether this restoration is favored by IFN-alpha treatment.
METHODS:
PD-1 and PD-L1 expression was studied on T cells and dendritic cells, respectively, of 14 patients with acute hepatitis C and different evolutions of infection. The effect of anti-PD-L1 was analyzed on proliferation, cytokine production and cytolytic activity of CD4 and CD8 T cells.
RESULTS:
While PD-1 expression dropped concurrently with spontaneous or IFN-alpha induced HCV-RNA decline, PD-L1 levels on dendritic cells increased during IFN-alpha treatment. Anti-PD-L1 antibodies improved expansion and cytokine production but not the cytolytic activity of HCV-specific T cells. This restoration tended to be greater at lower levels of viremia and PD-1 expression and during PEG-IFNalpha treatment.
CONCLUSIONS:
PD-1/PD-L1 blockade has an immunoregulatory activity which may synergize with the antiviral effect of IFN-alpha therapy and should be thus explored further in long-lasting chronic HCV infections in the perspective of improving the efficacy of available antiviral treatments. |
