Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers

F. Lechner, J. Sullivan, H. Spiegel, D. F. Nixon, B. Ferrari, A. Davis, B. Borkowsky, H. Pollack, E. Barnes, G. Dusheiko, P. Klenerman*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV-infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this 'CTL failure' are discussed.

Original languageEnglish
Pages (from-to)1085-1092
Number of pages8
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume355
Issue number1400
Publication statusPublished - 29 Aug 2000

Keywords

  • CD8
  • Cytotoxic T lymphocyte
  • Hepatitis C virus
  • Immune escape
  • Tetramer

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