Abstract
The anti-viral T cell response is believed to play a central role in the pathogenesis of hepatitis C virus infection. Since chronic evolution occurs in > 50% of HCV infections, the sequential analysis of the T cell response from the early clinical stages of disease may contribute to define the features of the T cell response associated with recovery or chronic viral persistence. For this purpose, 21 subjects with acute hepatitis C virus infection were sequentially followed for an average time of 44 wk. Twelve patients normalized transaminase values that remained normal throughout the follow-up period; all but two cleared hepatitis C virus-RNA from serum. The remaining nine patients showed persistent viremia and elevated transaminases. Analysis of the peripheral blood T cell proliferative response to core, E1, E2, NS3, NS4, and NS5 recombinant antigens and synthetic peptides showed that responses to all hepatitis C virus antigens, except E1, were significantly more vigorous and more frequently detectable in patients who normalized transaminase levels than in those who did not. By sequential evaluation of the T cell response, a difference between the two groups of patients was already detectable at the very early stages of acute infection and then maintained throughout the follow-up period. The results suggest that the vigor of the T cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection.
Full Text
The Full Text of this article is available as a PDF (224.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alter H. J. To C or not to C: these are the questions. Blood. 1995 Apr 1;85(7):1681–1695. [PubMed] [Google Scholar]
- Battegay M., Fikes J., Di Bisceglie A. M., Wentworth P. A., Sette A., Celis E., Ching W. M., Grakoui A., Rice C. M., Kurokohchi K. Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. J Virol. 1995 Apr;69(4):2462–2470. doi: 10.1128/jvi.69.4.2462-2470.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Botarelli P., Brunetto M. R., Minutello M. A., Calvo P., Unutmaz D., Weiner A. J., Choo Q. L., Shuster J. R., Kuo G., Bonino F. T-lymphocyte response to hepatitis C virus in different clinical courses of infection. Gastroenterology. 1993 Feb;104(2):580–587. doi: 10.1016/0016-5085(93)90430-k. [DOI] [PubMed] [Google Scholar]
- Brillanti S., Foli M., Gaiani S., Masci C., Miglioli M., Barbara L. Persistent hepatitis C viraemia without liver disease. Lancet. 1993 Feb 20;341(8843):464–465. doi: 10.1016/0140-6736(93)90210-8. [DOI] [PubMed] [Google Scholar]
- Cerny A., McHutchison J. G., Pasquinelli C., Brown M. E., Brothers M. A., Grabscheid B., Fowler P., Houghton M., Chisari F. V. Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. J Clin Invest. 1995 Feb;95(2):521–530. doi: 10.1172/JCI117694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diepolder H. M., Zachoval R., Hoffmann R. M., Wierenga E. A., Santantonio T., Jung M. C., Eichenlaub D., Pape G. R. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet. 1995 Oct 14;346(8981):1006–1007. doi: 10.1016/s0140-6736(95)91691-1. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Allan W., Eichelberger M., Carding S. R. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol. 1992;10:123–151. doi: 10.1146/annurev.iy.10.040192.001011. [DOI] [PubMed] [Google Scholar]
- Ferrari C., Bertoletti A., Penna A., Cavalli A., Valli A., Missale G., Pilli M., Fowler P., Giuberti T., Chisari F. V. Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen. J Clin Invest. 1991 Jul;88(1):214–222. doi: 10.1172/JCI115280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferrari C., Valli A., Galati L., Penna A., Scaccaglia P., Giuberti T., Schianchi C., Missale G., Marin M. G., Fiaccadori F. T-cell response to structural and nonstructural hepatitis C virus antigens in persistent and self-limited hepatitis C virus infections. Hepatology. 1994 Feb;19(2):286–295. [PubMed] [Google Scholar]
- Hoffmann R. M., Diepolder H. M., Zachoval R., Zwiebel F. M., Jung M. C., Scholz S., Nitschko H., Riethmüller G., Pape G. R. Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection. Hepatology. 1995 Mar;21(3):632–638. [PubMed] [Google Scholar]
- Kita H., Moriyama T., Kaneko T., Harase I., Nomura M., Miura H., Nakamura I., Yazaki Y., Imawari M. HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein. Hepatology. 1993 Nov;18(5):1039–1044. [PubMed] [Google Scholar]
- Koziel M. J., Dudley D., Afdhal N., Choo Q. L., Houghton M., Ralston R., Walker B. D. Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J Virol. 1993 Dec;67(12):7522–7532. doi: 10.1128/jvi.67.12.7522-7532.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koziel M. J., Dudley D., Wong J. T., Dienstag J., Houghton M., Ralston R., Walker B. D. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol. 1992 Nov 15;149(10):3339–3344. [PubMed] [Google Scholar]
- Lehmann P. V., Forsthuber T., Miller A., Sercarz E. E. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992 Jul 9;358(6382):155–157. doi: 10.1038/358155a0. [DOI] [PubMed] [Google Scholar]
- Lunel F. Hepatitis C virus and autoimmunity: fortuitous association or reality? Gastroenterology. 1994 Nov;107(5):1550–1555. doi: 10.1016/0016-5085(94)90564-9. [DOI] [PubMed] [Google Scholar]
- Minutello M. A., Pileri P., Unutmaz D., Censini S., Kuo G., Houghton M., Brunetto M. R., Bonino F., Abrignani S. Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J Exp Med. 1993 Jul 1;178(1):17–25. doi: 10.1084/jem.178.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paul W. E., Seder R. A. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. doi: 10.1016/0092-8674(94)90332-8. [DOI] [PubMed] [Google Scholar]
- Schupper H., Hayashi P., Scheffel J., Aceituno S., Paglieroni T., Holland P. V., Zeldis J. B. Peripheral-blood mononuclear cell responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C. Hepatology. 1993 Nov;18(5):1055–1060. [PubMed] [Google Scholar]
- Shirai M., Okada H., Nishioka M., Akatsuka T., Wychowski C., Houghten R., Pendleton C. D., Feinstone S. M., Berzofsky J. A. An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans. J Virol. 1994 May;68(5):3334–3342. doi: 10.1128/jvi.68.5.3334-3342.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuyver L., Rossau R., Wyseur A., Duhamel M., Vanderborght B., Van Heuverswyn H., Maertens G. Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol. 1993 Jun;74(Pt 6):1093–1102. doi: 10.1099/0022-1317-74-6-1093. [DOI] [PubMed] [Google Scholar]
- Urdea M. S., Horn T., Fultz T. J., Anderson M., Running J. A., Hamren S., Ahle D., Chang C. A. Branched DNA amplification multimers for the sensitive, direct detection of human hepatitis viruses. Nucleic Acids Symp Ser. 1991;(24):197–200. [PubMed] [Google Scholar]