CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection: A putative role for inflammatory cytokines

G. D'Agosto, E. Trento, L. Nosotti, V. Bordignon, M. Battista, G. Prignano, F. Pimpinelli, G. Biolcati, A. Macrí, G. Palamara, L. Miglioresi, A. Morrone, A. Di Carlo, Paola Cordiali-Fei, F. Ensoli

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-γ on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected subjects. In addition, the results strongly suggest that the cytokines released by activated lymphocytes at sites of inflammation may play a part in up-regulating CD81 expression.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalJournal of Biological Regulators and Homeostatic Agents
Volume23
Issue number3
Publication statusPublished - Jul 2009

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Chronic Hepatitis C
Virus Diseases
Hepacivirus
Lymphocytes
Cytokines
Porphyria Cutanea Tarda
HIV
Immunosuppressive Agents
Liver Transplantation
Up-Regulation
Phycoerythrin
Tacrolimus
Chronic Hepatitis
Natural Killer Cells
HIV Infections
Hepatocytes
Interleukin-6
Flow Cytometry
B-Lymphocytes
Therapeutics

Keywords

  • CD81
  • HCV
  • HIV
  • Porphyria Cutanea Tarda

ASJC Scopus subject areas

  • Oncology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Immunology and Allergy
  • Immunology
  • Endocrinology
  • Physiology
  • Cancer Research

Cite this

CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection : A putative role for inflammatory cytokines. / D'Agosto, G.; Trento, E.; Nosotti, L.; Bordignon, V.; Battista, M.; Prignano, G.; Pimpinelli, F.; Biolcati, G.; Macrí, A.; Palamara, G.; Miglioresi, L.; Morrone, A.; Di Carlo, A.; Cordiali-Fei, Paola; Ensoli, F.

In: Journal of Biological Regulators and Homeostatic Agents, Vol. 23, No. 3, 07.2009, p. 155-164.

Research output: Contribution to journalArticle

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abstract = "The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-γ on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected subjects. In addition, the results strongly suggest that the cytokines released by activated lymphocytes at sites of inflammation may play a part in up-regulating CD81 expression.",
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AU - Nosotti, L.

AU - Bordignon, V.

AU - Battista, M.

AU - Prignano, G.

AU - Pimpinelli, F.

AU - Biolcati, G.

AU - Macrí, A.

AU - Palamara, G.

AU - Miglioresi, L.

AU - Morrone, A.

AU - Di Carlo, A.

AU - Cordiali-Fei, Paola

AU - Ensoli, F.

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