Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity

Hepatology. 1997 Feb;25(2):449-58. doi: 10.1002/hep.510250233.


One striking clinical feature of hepatitis C virus (HCV) infection is that more than 50% of patients with acute hepatitis C will develop chronic infection. To investigate its possible mechanisms, we examined the activation of type 2-like T-helper (Th2-like) cells relating to the development of chronicity. Peripheral blood CD4+ T-cell proliferation and cytokine secretion in response to a panel of recombinant HCV antigens including core (C22), envelope 1 (E1), E2, nonstructural (NS) protein 4 (C100), fusion protein of NS3 and NS4 (C200), and NS5 were assayed in 17 patients with acute hepatitis C. All six patients with self-limited disease had a significant CD4+ T-cell proliferation to C22, E1, C100, C200, and NS5, running parallel with the antigen-stimulated secretion of interleukin (IL)-2 and interferon gamma (IFN-gamma), but not with interleukin (IL)-4 and IL-10, indicating predominant Th1 responses. Among the remaining 11 patients who developed chronicity, 6, 2, and 9 cases showed a specific CD4+ T-cell response to C22, C100, and C200, respectively, and the responses were significantly lower than those of cases with recovery in terms of stimulation index (SI) (P < .05) and of antigen-stimulated IL-2 and IFN-gamma production. Importantly, IL-4 and IL-10 (Th2 responses) were detectable, and C22-specific Th2-like T-cell clones could be generated from patients with chronicity. The data suggested that activation of Th2 responses in acute hepatitis C patients may play a role in the development of chronicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Hepatitis C / immunology*
  • Hepatitis, Chronic / immunology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / physiology


  • Interleukin-2
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma