Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Sep;97(3):403–410. doi: 10.1111/j.1365-2249.1994.tb06102.x

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B.

B N Pham 1, J F Mosnier 1, F Walker 1, C Njapoum 1, F Bougy 1, C Degott 1, S Erlinger 1, J H Cohen 1, F Degos 1
PMCID: PMC1534853  PMID: 7915977

Abstract

T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver-derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388 pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication, CD4+/CD8+ ratios of liver-derived lymphocytes were significantly higher (P < 0.05) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the gamma/delta receptor and that of CD2+/CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication, CD4+CD8+ ratios of liver-derived lymphocytes correlated with serum HBV DNA levels (P < 0.001). No relationship between CD4+/CD8+ ratio of liver-derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B, the CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytotoxic T cell activity in patients with HBV-related chronic hepatitis.

Full text

PDF
403

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander G. J., Mondelli M., Naumov N. V., Nouriaria K. T., Vergani D., Lowe D., Eddleston A. L., Williams R. Functional characterization of peripheral blood lymphocytes in chronic HBsAg carriers. Clin Exp Immunol. 1986 Mar;63(3):498–507. [PMC free article] [PubMed] [Google Scholar]
  2. Carella G., Chatenoud L., Degos F., Bach M. A. Regulatory T cell-subset imbalance in chronic active hepatitis. J Clin Immunol. 1982 Apr;2(2):93–100. doi: 10.1007/BF00916892. [DOI] [PubMed] [Google Scholar]
  3. Chu C. M., Liaw Y. F. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis. Gastroenterology. 1987 Jan;92(1):220–225. doi: 10.1016/0016-5085(87)90863-8. [DOI] [PubMed] [Google Scholar]
  4. Colucci G., Colombo M., Del Ninno E., Paronetto F. In situ characterization by monoclonal antibodies of the mononuclear cell infiltrate in chronic active hepatitis. Gastroenterology. 1983 Nov;85(5):1138–1145. [PubMed] [Google Scholar]
  5. Ferrari C., Penna A., Giuberti T., Tong M. J., Ribera E., Fiaccadori F., Chisari F. V. Intrahepatic, nucleocapsid antigen-specific T cells in chronic active hepatitis B. J Immunol. 1987 Sep 15;139(6):2050–2058. [PubMed] [Google Scholar]
  6. Ferrari C., Penna A., Sansoni P., Giuberti T., Neri T. M., Chisari F. V., Fiaccadori F. Selective sensitization of peripheral blood T lymphocytes to hepatitis B core antigen in patients with chronic active hepatitis type B. Clin Exp Immunol. 1986 Dec;66(3):497–506. [PMC free article] [PubMed] [Google Scholar]
  7. Han K. H., Hollinger F. B., Noonan C. A., Yoffe B. Simultaneous detection of HBV-specific antigens and DNA in paraffin-embedded liver tissue by immunohistochemistry and in situ hybridization using a digoxigenin-labeled probe. J Virol Methods. 1992 Apr;37(1):89–97. doi: 10.1016/0166-0934(92)90023-7. [DOI] [PubMed] [Google Scholar]
  8. Hata K., Van Thiel D. H., Herberman R. B., Whiteside T. L. Natural killer activity of human liver-derived lymphocytes in various liver diseases. Hepatology. 1991 Sep;14(3):495–503. [PubMed] [Google Scholar]
  9. Hata K., Van Thiel D. H., Herberman R. B., Whiteside T. L. Phenotypic and functional characteristics of lymphocytes isolated from liver biopsy specimens from patients with active liver disease. Hepatology. 1992 May;15(5):816–823. doi: 10.1002/hep.1840150512. [DOI] [PubMed] [Google Scholar]
  10. Knodell R. G., Ishak K. G., Black W. C., Chen T. S., Craig R., Kaplowitz N., Kiernan T. W., Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981 Sep-Oct;1(5):431–435. doi: 10.1002/hep.1840010511. [DOI] [PubMed] [Google Scholar]
  11. Kuhns M. C., McNamara A. L., Perrillo R. P., Cabal C. M., Campbel C. R. Quantitation of hepatitis B viral DNA by solution hybridization: comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy. J Med Virol. 1989 Apr;27(4):274–281. doi: 10.1002/jmv.1890270404. [DOI] [PubMed] [Google Scholar]
  12. Milich D. R., McLachlan A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science. 1986 Dec 12;234(4782):1398–1401. doi: 10.1126/science.3491425. [DOI] [PubMed] [Google Scholar]
  13. Mondelli M. U., Bortolotti F., Pontisso P., Rondanelli E. G., Williams R., Realdi G., Alberti A., Eddleston A. L. Definition of hepatitis B virus (HBV)-specific target antigens recognized by cytotoxic T cells in acute HBV infection. Clin Exp Immunol. 1987 May;68(2):242–250. [PMC free article] [PubMed] [Google Scholar]
  14. Montaño L., Aranguibel F., Boffill M., Goodall A. H., Janossy G., Thomas H. C. An analysis of the composition of the inflammatory infiltrate in autoimmune and hepatitis B virus-induced chronic liver disease. Hepatology. 1983 May-Jun;3(3):292–296. doi: 10.1002/hep.1840030303. [DOI] [PubMed] [Google Scholar]
  15. Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
  16. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  17. Naumov N. V., Mondelli M., Alexander G. J., Tedder R. S., Eddleston A. L., Williams R. Relationship between expression of hepatitis B virus antigens in isolated hepatocytes and autologous lymphocyte cytotoxicity in patients with chronic hepatitis B virus infection. Hepatology. 1984 Jan-Feb;4(1):63–68. doi: 10.1002/hep.1840040111. [DOI] [PubMed] [Google Scholar]
  18. Pape G. R., Rieber E. P., Eisenburg J., Hoffmann R., Balch C. M., Paumgartner G., Riethmüller G. Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases. Gastroenterology. 1983 Sep;85(3):657–662. [PubMed] [Google Scholar]
  19. Pignatelli M., Waters J., Lever A., Iwarson S., Gerety R., Thomas H. C. Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection. J Hepatol. 1987 Feb;4(1):15–21. doi: 10.1016/s0168-8278(87)80004-1. [DOI] [PubMed] [Google Scholar]
  20. Ramalho F., Brunetto M. R., Rocca G., Piccari G. G., Batista A., Chiaberge E., Lavarini C., Dal Monte R. P., Carneiro de Moura M., Bonino F. Serum markers of hepatitis B virus replication, liver histology and intrahepatic expression of hepatitis B core antigen. J Hepatol. 1988 Aug;7(1):14–20. doi: 10.1016/s0168-8278(88)80502-6. [DOI] [PubMed] [Google Scholar]
  21. Regenstein F. G., Roodman S. T., Perrillo R. P. Immunoregulatory T cell subsets in chronic hepatitis B virus infection: the influence of homosexuality. Hepatology. 1983 Nov-Dec;3(6):951–954. doi: 10.1002/hep.1840030612. [DOI] [PubMed] [Google Scholar]
  22. Suppressor cell function in chronic liver disease. Lancet. 1983 Aug 6;2(8345):342–343. [PubMed] [Google Scholar]
  23. Thomas H. C., Brown D., Routhier G., Janossy G., Kung P. C., Goldstein G., Sherlock S. Inducer and suppressor T-cells in hepatitis B virus-induced liver disease. Hepatology. 1982 Mar-Apr;2(2):202–204. doi: 10.1002/hep.1840020203. [DOI] [PubMed] [Google Scholar]
  24. Vento S., Hegarty J. E., Alberti A., O'Brien C. J., Alexander G. J., Eddleston A. L., Williams R. T lymphocyte sensitization to HBcAg and T cell-mediated unresponsiveness to HBsAg in hepatitis B virus-related chronic liver disease. Hepatology. 1985 Mar-Apr;5(2):192–197. doi: 10.1002/hep.1840050206. [DOI] [PubMed] [Google Scholar]
  25. Yang P. M., Su I. J., Lai M. Y., Huang G. T., Hsu H. C., Chen D. S., Sung J. L. Immunohistochemical studies on intrahepatic lymphocyte infiltrates in chronic type B hepatitis, with special emphasis on the activation status of the lymphocytes. Am J Gastroenterol. 1988 Sep;83(9):948–953. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES