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PD-1 : PD-L1 interactions contribute to the functional suppression of virus-specific CD8(+) T lymphocytes in the liver

Academic Article
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Overview

authors

  • Maier, H.
  • Isogawa, Masanori
  • Freeman, G. J.
  • Chisari, Francis

publication date

  • March 2007

journal

  • Journal of Immunology  Journal

abstract

  • Mechanisms contributing to the development of chronic viral infections, including chronic hepatitis B virus (HBV) infections, are not well understood. We have shown recently that production of IFN-gamma, an important antiviral cytokine, by HBV-specific CTLs is rapidly induced when they enter the liver of HBV transgenic mice, and then rapidly suppressed, despite the continued presence of Ag. Suppression of IFN-gamma production by the CTLs coincides with the up-regulation of programmed cell death (PD)-1, a cell surface signaling molecule known to inhibit T cell function. To determine whether PD-1 plays a role in the functional suppression of IFN-gamma secretion by CTLs, we treated HBV transgenic mice with blocking Abs specific for PD ligand (PD-L)1, the most widely expressed PD-1 ligand, and adoptively transferred HBV-specific CTLs. Treatment with anti-PD-L1 Abs resulted in a delay in the suppression of IFN-gamma-producing CTLs and a concomitant increase in the absolute number of IFN-gamma-producing CTLs in the liver. These results indicate that PD-1:PD-L1 interactions contribute to the suppression of IFN-gamma secretion observed following Ag recognition in the liver. Blockade of inhibitory pathways such as PD-1:PD-L1 may reverse viral persistence and chronic infection in cases in which the CTL response is suppressed by this mechanism.

subject areas

  • Animals
  • Antibodies
  • Antigens, CD274
  • Antigens, CD80
  • Antigens, Differentiation
  • CD8-Positive T-Lymphocytes
  • Cells, Cultured
  • Hepatitis B Antigens
  • Hepatitis B virus
  • Hepatitis B, Chronic
  • Humans
  • Immune Tolerance
  • Interferon-gamma
  • Liver
  • Membrane Glycoproteins
  • Mice
  • Mice, Transgenic
  • Peptides
  • Programmed Cell Death 1 Receptor
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 17312113
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Additional Document Info

start page

  • 2714

end page

  • 2720

volume

  • 178

issue

  • 5

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