Detection of Antigen-Specific CD8+ T Cells in the Livers of HCV Core Transgenic Mice

  • Dustin A. Cobb
  • Aditya P. Dandekar
  • Young S. HahnEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1911)


Hepatitis C virus-mediated immune suppression is an underlying feature leading to the establishment of viral persistence and chronic infection. In particular, HCV core protein has been shown to exhibit significant immunosuppressive activity of T cells and antigen presenting cells. Using an HCV core transgenic mouse system, in which liver hepatocytes express core protein, it is possible to study the effects of core-mediated immune suppression in vivo during viral infection. In this protocol, we describe the procedures for evaluating antigen-specific CD8+ T cell responses in response to recombinant adenovirus infection in HCV core transgenic mice.

Key words

Hepatitis C virus CD8 T cells Liver Core protein Antiviral T cells Liver mononuclear cell isolation Flow cytometry Tetramer 



This work was supported by the National Institutes of Health. (Grants AI098126 and U19 AI066328 to Y.S.H.; T32AI007496 to DAC)


  1. 1.
    Afdhal NH (2004) The natural history of hepatitis C. Semin Liver Dis 24(Suppl 2):3–8CrossRefGoogle Scholar
  2. 2.
    Dustin LB, Rice CM (2007) Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol 25:71–99CrossRefGoogle Scholar
  3. 3.
    Abdel-Hakeem MS, Shoukry NH (2014) Protective immunity against hepatitis C: many shades of gray. Front Immunol 5:274CrossRefGoogle Scholar
  4. 4.
    Large MK, Kittlesen DJ, Hahn YS (1999) Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence. J Immunol 162:931–938PubMedGoogle Scholar
  5. 5.
    Sarobe P, Lasarte JJ, Casares N, Lopez-Diaz de Cerio A, Baixeras E, Labarga P et al (2002) Abnormal priming of CD4(+) T cells by dendritic cells expressing hepatitis C virus core and E1 proteins. J Virol 76:5062–5070CrossRefGoogle Scholar
  6. 6.
    Zhang B, Yin Y, Lai RC, Lim SK (2014) Immunotherapeutic potential of extracellular vesicles. Front Immunol 5:518PubMedPubMedCentralGoogle Scholar
  7. 7.
    Yao ZQ, Nguyen DT, Hiotellis AI, Hahn YS (2001) Hepatitis C virus core protein inhibits human T lymphocyte responses by a complement-dependent regulatory pathway. J Immunol 167:5264–5272CrossRefGoogle Scholar
  8. 8.
    Eisen-Vandervelde AL, Waggoner SN, Yao ZQ, Cale EM, Hahn CS, Hahn YS (2004) Hepatitis C virus core selectively suppresses interleukin-12 synthesis in human macrophages by interfering with AP-1 activation. J Biol Chem 279:43479–43486CrossRefGoogle Scholar
  9. 9.
    Lukens JR, Cruise MW, Lassen MG, Hahn YS (2008) Blockade of PD-1/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model. J Immunol 180:4875–4884CrossRefGoogle Scholar
  10. 10.
    Krebs P, Scandella E, Odermatt B, Ludewig B (2005) Rapid functional exhaustion and deletion of CTL following immunization with recombinant adenovirus. J Immunol 174:4559–4566CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dustin A. Cobb
    • 1
  • Aditya P. Dandekar
    • 1
  • Young S. Hahn
    • 1
    • 2
    Email author
  1. 1.Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleUSA

Personalised recommendations