Original Article

T-cell–mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection

  1. Yun-Fan Liaw1,
  2. Ching-Song Lee1,
  3. Sun-Lung Tsai1,
  4. Bo-Wen Liaw MD1,*,
  5. Tse-Ching Chen2,
  6. I-Shyan Sheen1,
  7. Chia-Ming Chu1

Article first published online: 5 DEC 2005

DOI: 10.1002/hep.1840220505

Issue

Hepatology

Hepatology

Volume 22, Issue 5, pages 1368–1373, November 1995

Additional Information

How to Cite

Liaw, Y.-F., Lee, C.-S., Tsai, S.-L., Liaw, B.-W., Chen, T.-C., Sheen, I.-S. and Chu, C.-M. (1995), T-cell–mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection. Hepatology, 22: 1368–1373. doi: 10.1002/hep.1840220505

Author Information

  1. 1

    Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung Medical College, Taipei, Taiwan

  2. 2

    Department of Pathology, Chang Gung Memorial Hospital and Chang Gung Medical College, Taipei, Taiwan

*Liver Research Unit, Chang Gung Memorial Hospital, 199, Tung Hwa North Rd, Taipei, Taiwan 105

Publication History

  1. Issue published online: 5 DEC 2005
  2. Article first published online: 5 DEC 2005
  3. Manuscript Accepted: 30 JUN 1995
  4. Manuscript Received: 7 JUN 1995

Funded by

  • National Science Council, Taiwan. Grant Numbers: NSC81-0419-B-182A-502, NSC83-0419-B-182-002 MH, NSC84-2331-B-182-049 MH
  • Prosperous Foundation, Taipei, Taiwan

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Abstract

Virus-specific cytotoxic T lymphocytes (CTLs) have been suggested to be responsible for the liver injuries in patients with hepatitis C virus (HCV) infection. However, there has been no report of direct evidence to substantiate this hypothesis. In this study, we performed in vitro autologous hepatocytotoxicity assay in 45 patients to examine a possible role of CTLs to HCV-in-fected liver cells. The data were correlated with histology activity index of liver biopsy specimens. Lymphocyte subsets and hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II) were also evaluated. The immunohistochemical study showed more prominent HLA-I expression than HLA-II on hepatocytes (mean score ± SEM: 2.34 ± 0.11 vs. 0.42 ± 0.08; P < .01). The lymphocyte subset analysis showed that CD8+ T cells were dominant in the lobular areas showing spotty necrosis, whereas CD4+ T cells were prominent in the portal and periportal areas (P < .01). Most patients had a significant T cell-mediated cytotoxicity to hepatocytes as compared with non-T cells (percentage cytotoxicity ± SEM: 46.4 ± 2.3 vs. 13.8 ± 2.7; P < .001). T cell-mediated hepatocytotoxicity had a linear correlation with HAI (P < .05). The T cell-mediated cytotoxicity could be blocked by anti-CD8 (43.7% vs. 9.5%, P < .05) or by anti-HLA-I (43.7% vs. 18.5%, P < .05) but not by anti-CD4 or anti-HLA-II monoclonal antibodies. These findings strongly suggest that HLA-I–restricted, CD8+ T cell–mediated hepatocytotoxicity is an important pathogenetic mechanism in patients with chronic HCV infection. (Hepatology 1995; 22:1368–1373).

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