Differential CD4+ and CD8+ T-cell responsiveness in hepatitis C virus infection
Article first published online: 30 DEC 2003
Copyright © 2001 American Association for the Study of Liver Diseases
Volume 33, Issue 1, pages 267–276, January 2001
How to Cite
Chang, K.-M., Thimme, R., Melpolder, J. J., Oldach, D., Pemberton, J., Moorhead-Loudis, J., McHutchison, J. G., Alter, H. J. and Chisari, F. V. (2001), Differential CD4+ and CD8+ T-cell responsiveness in hepatitis C virus infection. Hepatology, 33: 267–276. doi: 10.1053/jhep.2001.21162
- Issue published online: 30 DEC 2003
- Article first published online: 30 DEC 2003
- Manuscript Accepted: 24 OCT 2000
- Manuscript Received: 19 JUL 2000
- NIH and the Sam and Rose Stein Endowment fund. Grant Numbers: AI20001, MO1 RR00833
- American Liver Foundation Amgen Postdoctoral Supplementary Research Fellowship Award, the Amgen/AASLD/ALF Research Development Award, AI47519-01 and AA12849-01 K.M.C.
- Deutsche Forschungsgemeinschaft, Bonn, Germany (R.T.). Grant Number: TH 719/1-1
This study was performed to compare the vigor and phenotype of virus-specific CD4+ and CD8+ T-cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4+ proliferative T-cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV-specific CD8+ T-cell response was quantitatively low in both groups despite the use of sensitive direct ex vivo intracellular interferon gamma (IFN-γ) staining. Furthermore, although HCV-specific cytolytic CD8+ memory T cells were undetectable ex vivo, they were readily expanded from the peripheral blood of chronically HCV-infected patients but not from recovered subjects after in vitro stimulation, suggesting that ongoing viremia is required to maintain the HCV-specific memory CD8+ T-cell response. HCV-specific CD8+ T cells displayed a type 1 cytokine profile characterized by production of IFN-γ despite persistent HCV viremia. The paradoxical observation that HCV-specific CD4+ T cells survive and CD8+ T cells are lost after viral clearance while the opposite occurs when HCV persists suggests the existence of differential requirements for the maintenance of CD4+ and CD8+ T-cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8+ effector T cells in chronically infected patients may explain the chronic insidious nature of the liver inflammation and also why they fail to eliminate the virus.