Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1978 Aug;21(2):480–488. doi: 10.1128/iai.21.2.480-488.1978

Hepatitis B surface antigen-specific cell-mediated immune responses in human chronic hepatitis B surface antigen carriers.

K R Beutner, M L Tiku, P L Ogra
PMCID: PMC422021  PMID: 80380

Abstract

The presence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), the nature of T-cell function, and specific cell-mediated immunity to HBsAg were determined and evaluated serially in groups of subjects with chronic HBsAg carrier states and in seronegative controls. The techniques of in vitro lymphocyte transformation, spontaneous rosette formation, radioimmunoassay, reverse passive hemagglutination, passive hemagglutination, rheophoresis, and liver function tests were employed for these studies. For the lymphocyte transformation assay, multiple concentrations of phytohemagglutinin and purified HBsAg were used as stimulants. Cell-mediated immunity to HBsAg was detectable in 50% of the chronic HBsAg carriers (responders) at one or more concentrations of HBsAg. The remaining carriers (nonresponders) and controls failed to manifest HBsAg-specific lymphocyte transformation activity. The profile of the responders was characterized by elevated serum glutamic pyruvic transaminase levels, the presence of anti-HBe, high HBsAg titers, and the conspicuous absence of HBeAg in the serum. The nonresponders were characterized by normal serum glutamic pyruvic transaminase levels, the presence of HBeAg and anti-HBe, and lower HBsAg titers. These observations demonstrate the presence of specific cell-mediated immunity to HBsAg in chronic HBsAg carriers who manifest biochemical evidence of liver disease.

Full text

PDF
480

Selected References

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

  1. Anderson K. E., Sun S. C., Berg H. S., Chang N. K. Liver function and histology in asymptomatic Chinese military personnel with hepatitis B antigenemia. Am J Dig Dis. 1974 Aug;19(8):693–703. doi: 10.1007/BF01844938. [DOI] [PubMed] [Google Scholar]
  2. Cayzer I., Dane D. S., Cameron C. H., Denning J. V. A rapid haemagglutination test for hepatitis-B antigen. Lancet. 1974 May 18;1(7864):947–949. doi: 10.1016/s0140-6736(74)91259-8. [DOI] [PubMed] [Google Scholar]
  3. Cherubin C. E., Rosenthal W. S., Stenger R. E., Prince A. M., Baden M., Strauss R., McGinn T. G. Chronic liver disease in asymptomatic narcotic addicts. Ann Intern Med. 1972 Mar;76(3):391–395. doi: 10.7326/0003-4819-76-3-391. [DOI] [PubMed] [Google Scholar]
  4. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. I. Quantitative isolation of human T and B cells and response to mitogens. J Immunol. 1974 Oct;113(4):1113–1121. [PubMed] [Google Scholar]
  5. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. II. Antigen triggering of T and B cells in vitro. J Immunol. 1974 Oct;113(4):1122–1127. [PubMed] [Google Scholar]
  6. Dudley F. J., Giustino V., Sherlock S. Cell-mediated immunity in patients positive for hepatitis-associated antigen. Br Med J. 1972 Dec 30;4(5843):754–756. doi: 10.1136/bmj.4.5843.754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eleftheriou N., Thomas H. C., Heathcote J., Sherlock S. Incidence and clinical significance of e antigen and antibody in acute and chronic liver disease. Lancet. 1975 Dec 13;2(7946):1171–1173. doi: 10.1016/s0140-6736(75)92657-4. [DOI] [PubMed] [Google Scholar]
  8. Feinman S. V., Berris B., Sinclair J. C., Wrobel D. M., Murphy B. L., Maynard J. E. e antigen and anti-e in HBsAg carriers. Lancet. 1975 Dec 13;2(7946):1173–1174. doi: 10.1016/s0140-6736(75)92658-6. [DOI] [PubMed] [Google Scholar]
  9. Gerber M. A., Hadziyannis S., Vissoulis C., Schaffner F., Paronetto F., Popper H. Electron microscopy and immunoelectronmicroscopy of cytoplasmic hepatitis B antigen in hepatocytes. Am J Pathol. 1974 Jun;75(3):489–502. [PMC free article] [PubMed] [Google Scholar]
  10. Gerber M. J., Phuangsab A., Vittal S. B., Dourdourekas D., Steigmann F., Clowdus B. F. Cell-mediated immune response to hepatitis B antigen in patients with liver disease. Am J Dig Dis. 1974 Jul;19(7):637–643. doi: 10.1007/BF01073019. [DOI] [PubMed] [Google Scholar]
  11. Gocke D. J., Howe C. Rapid detection of Australia antigen by counterimmunoelectrophoresis. J Immunol. 1970 Apr;104(4):1031–1034. [PubMed] [Google Scholar]
  12. Hadziyannis S., Gerber M. A., Vissoulis C., Popper H. Cytoplasmic hepatitis B antigen in "ground-glass" hepatocytes of carriers. Arch Pathol. 1973 Nov;96(5):327–330. [PubMed] [Google Scholar]
  13. Hepburn B., Ritts R. E., Jr Human T lymphocytes: assay method using permanently fixed slides. Mayo Clin Proc. 1974 Nov;49(11):866–869. [PubMed] [Google Scholar]
  14. Hosking C. S., Fitzgerald M. G., Simons M. J. Quantified deficiency of lymphocyte response to phytohaemagglutinin in immune deficiency diseases. Clin Exp Immunol. 1971 Oct;9(4):467–476. [PMC free article] [PubMed] [Google Scholar]
  15. Ibrahim A. B., Vyas G. N., Perkins H. A. Immune response to hepatitis B surface antigen. Infect Immun. 1975 Jan;11(1):137–141. doi: 10.1128/iai.11.1.137-141.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Irwin G. R., Jr, Hierholzer W. J., Jr, Cimis R., McCollum R. W. Delayed hypersensitivity in hepatitis B: clinical correlates of in vitro production of migration inhibition factor. J Infect Dis. 1974 Dec;130(6):580–587. doi: 10.1093/infdis/130.6.580. [DOI] [PubMed] [Google Scholar]
  17. Ito K., Nakagawa J., Okimoto Y., Nakano H. Chronic hepatitis--migration inhibition of leukocytes in the presence of Australia antigen. N Engl J Med. 1972 May 4;286(18):1005–1005. doi: 10.1056/nejm197205042861817. [DOI] [PubMed] [Google Scholar]
  18. Lee W. M., Reed W. D., Mitchell C. G., Woolf I. L., Dymock I. W., Eddleston A. L., Williams R. Cell-mediated immunity to hepatitis B surface antigen in blood donors with persistent antigenaemia. Gut. 1975 Jun;16(6):416–420. doi: 10.1136/gut.16.6.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ling C. M., Overby L. R. Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody. J Immunol. 1972 Oct;109(4):834–841. [PubMed] [Google Scholar]
  20. Magnius L. O., Lindholm A., Lundin P., Iwarson S. A new antigen-antibody system. Clinical significance in long-term carriers of hepatitis B surface antigen. JAMA. 1975 Jan 27;231(4):356–359. doi: 10.1001/jama.231.4.356. [DOI] [PubMed] [Google Scholar]
  21. Maynard J. E., Barrett D. H., Murphy B. L., Bradley D. W., Berquist K. R., Bender T. R. Relation of e antigen to hepatitis B virus infection in an area of hyperendemicity. J Infect Dis. 1976 Mar;133(3):339–342. doi: 10.1093/infdis/133.3.339. [DOI] [PubMed] [Google Scholar]
  22. Mistretta A. P., Golferini A., Tassi G. C., De Barbierri A. Identification of some HBAg (HAA) antigenic determinants by two-dimensional electro-immunodiffusion. J Biol Stand. 1974 Oct;2(4):313–318. doi: 10.1016/0092-1157(74)90040-7. [DOI] [PubMed] [Google Scholar]
  23. Morag A., Morag B., Bernstein J. M., Beutner K., Ogra P. L. In vitro correlates of cell-mediated immunity in human tonsils after natural or induced Rubella virus infection. J Infect Dis. 1975 Apr;131(4):409–416. doi: 10.1093/infdis/131.4.409. [DOI] [PubMed] [Google Scholar]
  24. Nielsen J. O., Dietrichson O., Juhl E. Incidence and meaning of the "e" determinant among hepatitis-B-antigen positive patients with acute and chronic liver diseases. Report from the Copenhagen Hepatitis Acuta Programme. Lancet. 1974 Oct 19;2(7886):913–915. doi: 10.1016/s0140-6736(74)91127-1. [DOI] [PubMed] [Google Scholar]
  25. Oppenheim J. J., Blaese R. M., Waldmann T. A. Defective lymphocyte transformation and delayed hypersensitivity in Wiskott-Aldrich syndrome. J Immunol. 1970 Apr;104(4):835–844. [PubMed] [Google Scholar]
  26. Pauly J. L., Han T. Whole blood microculture assay of human lymphocyte function. J Lab Clin Med. 1976 Nov;88(5):864–872. [PubMed] [Google Scholar]
  27. Popper H. Clinical pathologic correlation in viral hepatitis. The effect of the virus on the liver. Am J Pathol. 1975 Dec;81(3):609–628. [PMC free article] [PubMed] [Google Scholar]
  28. Redeker A. G. Viral hepatitis: clinical aspects. Am J Med Sci. 1975 Jul-Aug;270(1):9–16. doi: 10.1097/00000441-197507000-00003. [DOI] [PubMed] [Google Scholar]
  29. Simon J. B., Patel S. K. Liver diseases in asymptomatic carriers of hepatitis B antigen. Gastroenterology. 1974 May;66(5):1020–1028. [PubMed] [Google Scholar]
  30. Tong M. J., Wallace A. M., Peters R. L., Reynolds T. B. Lymphocyte stimulation in hepatitis B infections. N Engl J Med. 1975 Aug 14;293(7):318–322. doi: 10.1056/NEJM197508142930702. [DOI] [PubMed] [Google Scholar]
  31. Vyas G. N., Shulman N. R. Hemagglutination assay for antigen and antibody associated with viral hepatitis. Science. 1970 Oct 16;170(3955):332–333. doi: 10.1126/science.170.3955.332. [DOI] [PubMed] [Google Scholar]
  32. Woolf I. L., Boyes B. E., Jones D. M., Whittaker J. S., Tapp E., MacSween R. N., Renton P. H., Stratton F., Dymock I. W. Asymptomatic liver disease in hepatitis B antigen carriers. J Clin Pathol. 1974 May;27(5):348–352. doi: 10.1136/jcp.27.5.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. de Gast G. C., Houwen B., Nieweg H. O. Specific lymphocyte stimulation by purified, heat-inactivated hepatitis-B antigen. Br Med J. 1973 Dec 22;4(5894):707–709. doi: 10.1136/bmj.4.5894.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. de Moura M. C., Vernace S. J., Paronetto F. Cell-mediated immune reactivity to hepatitis B surface antigen in liver diseases. Gastroenterology. 1975 Aug;69(2):310–317. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES