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. 2008 Mar;82(6):3154-60.
doi: 10.1128/JVI.02474-07. Epub 2007 Dec 26.

High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome

Victoria Kasprowicz  1 , Julian Schulze Zur Wiesch, Thomas Kuntzen, Brian E Nolan, Steven Longworth, Andrew Berical, Jenna Blum, Cory McMahon, Laura L Reyor, Nahel Elias, William W Kwok, Barbara G McGovern, Gordon Freeman, Raymond T Chung, Paul Klenerman, Lia Lewis-Ximenez, Bruce D Walker, Todd M Allen, Arthur Y Kim, Georg M Lauer
Affiliations

High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome

Victoria Kasprowicz et al. J Virol. 2008 Mar.

Erratum in

  • J Virol. 2011 May;85(9):4633

Abstract

We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8(+) and CD4(+) T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection.

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Figures

FIG. 1.
FIG. 1.
High PD-1 expression levels in the acute and chronic phases of HCV infection. (A) PD-1 expression levels on HCV-specific CD8+ T-cell populations during the acute stage of HCV infection. For clarity, only data from the first available time point are displayed on the graph. Open symbols indicate individuals with chronically evolving acute infections, while filled symbols indicate individuals with self-limiting infections. (B) PD-1 expression levels on HCV-specific CD4+ T-cell populations during the acute stage of infection. The graph shows data for six HCV-specific CD4+ T-cell responses from three individuals with chronically evolving HCV infections and four HCV-specific CD4+ T-cell responses from three individuals with self-limiting courses of infection. (C) High PD-1 expression levels can be seen on HCV-specific cells from both long-term chronically infected individuals and individuals with documented resolved infections. The left panel shows data as analyzed by percent positive PD-1 expression, and the right panel represents the data as analyzed by MFI. (D) PD-1 expression levels on HCV-specific CD4+ T cells from individuals with resolved infections. (E) Increased proliferation of HCV-specific CD8+ T cells in the presence of anti PD-L1. Individual 01-49 targets two epitopes (NS3 1406-1415 and NS5A 1987-1996). The addition of anti-PDL1 alone resulted in a 14-fold increase in NS3 1406-1415-specific T-cell proliferation and a 60-fold increase in NS5A 1987-1996-specific T-cell proliferation.
FIG. 2.
FIG. 2.
PD-1 expression on individual T-cell populations is partially associated with viral load in the acute phase of infection. Longitudinal PD-1 expression levels on the DR0401-124 CD4+ T-cell population from individual 05H (left panel). The clinical course of the acute infection is displayed in the right panel. Subject 05H cleared acute HCV infection following the administration of antiviral therapy. Two HCV-specific T-cell populations were tracked in this individual: NS5B 2841-2849 CD8+ T cells and DR0401-124 CD4+ T cells.
FIG. 3.
FIG. 3.
PD-1 expression levels on bulk and liver-infiltrating CD8+ and CD4+ T cells. PD-1 expression levels on peripheral and liver-infiltrating CD8+ (A) and CD4+ (B) T cells from chronically infected individuals. Significantly higher levels were found on liver-infiltrating CD8+ and CD4+ lymphocytes compared to peripheral blood levels (P < 0.0001 and P < 0.0001, respectively). (C) PD-1 expression levels on 10 HCV-specific CD8+ liver-infiltrating T-cell populations from seven chronically infected individuals. Also shown are the PD-1 expression levels on two HBV-specific CD8+ T cell populations from one chronically HBV-infected individual and one Epstein-Barr virus-specific population. (D) PD-1 expression levels are displayed for liver, lymph node, and PBMC samples from individual 00-26. PD-1 expression levels were increased in liver compared to that in periphery on both the HCV-specific population and bulk CD8+ T-cell population.
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