Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis

Jayaprakash Sreenarasimhaiah, Andrés Jaramillo, Jeffrey Crippin, Mauricio Lisker-Melman, William C. Chapman, T. Mohanakumar

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8+ T cells reactive to 12 HCV-derived epitopes was determined by an interferon-γ enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4+ Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-γ and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8+ T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4+ Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.

Original languageEnglish (US)
Pages (from-to)224-230
Number of pages7
JournalHuman Immunology
Volume64
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • CD4 T cells
  • CD8 T cells
  • Chronic infection
  • Cirrhosis
  • Hepatitis C virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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