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-a 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-a induced HCV–RNA decline, PD-L1 levels on dendritic cells increased during IFN-a 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-IFNa treatment. Conclusions:PD-1/PD-L1 blockade has an immunoregulatory activity which may synergize with the antiviral effect of IFN-a therapy and should be thus explored further in long-lasting chronic HCV infections in the perspective of improving the efficacy of available antiviral treatments.

Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment / Urbani, Simona; Amadei, Barbara; Tola, Daniela; Pedrazzi, Giuseppe; Sacchelli, Luca; Cavallo, Maria Cristina; Orlandini, Alessandra; Missale, Gabriele; Ferrari, Carlo. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 48:(2008), pp. 548-558. [10.1016/j.jhep.2007.12.014]

Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment.

PEDRAZZI, Giuseppe;Missale, Gabriele;FERRARI, Carlo
2008-01-01

Abstract

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-a 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-a induced HCV–RNA decline, PD-L1 levels on dendritic cells increased during IFN-a 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-IFNa treatment. Conclusions:PD-1/PD-L1 blockade has an immunoregulatory activity which may synergize with the antiviral effect of IFN-a therapy and should be thus explored further in long-lasting chronic HCV infections in the perspective of improving the efficacy of available antiviral treatments.
2008
Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment / Urbani, Simona; Amadei, Barbara; Tola, Daniela; Pedrazzi, Giuseppe; Sacchelli, Luca; Cavallo, Maria Cristina; Orlandini, Alessandra; Missale, Gabriele; Ferrari, Carlo. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 48:(2008), pp. 548-558. [10.1016/j.jhep.2007.12.014]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1830736
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