Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1982 Feb;47(2):351–358.

Alterations of T-cell subsets in primary biliary cirrhosis.

A K Bhan, J L Dienstag, J R Wands, S F Schlossman, E L Reinherz
PMCID: PMC1536516  PMID: 6210473

Abstract

To determine whether abnormalities of immunoregulatory T cells are associated with primary biliary cirrhosis, we characterized peripheral blood mononuclear cells in 16 patients with primary biliary cirrhosis and compared them with 30 normal controls. For this analysis we used monoclonal antibodies to the surface antigens on helper/inducer (T4+) and suppressor (T8+) T cell subsets and to a common T cell antigen (T3+). In contrast to normal persons, patients with primary biliary cirrhosis had reduced percentages of T3+ cells. More importantly, there was a relative decrease in helper/inducer (T4+) cells in 9/16 patients and a decrease in suppressor (T8+) cells in 5/16 patients. Furthermore, clinical studies indicated that patients with a decreased suppressor cell population (increased T4+ : T8+ ratio) had more advanced disease, as reflected by serum bilirubin levels (P less than 0.05) and histological changes in the liver (P less than 0.001), than those patients with a reduced helper T cell population (decreased T4+ : T8+ ratio). These data suggest that abnormalities of immune responsiveness in primary biliary cirrhosis may have a more complex origin than a uniform alteration in one immunoregulatory T-cell subset and that these immunoregulatory cell changes vary according to the severity of the disease.

Full text

PDF
354

Selected References

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

  1. Bhan A. K., Reinherz E. L., Poppema S., McCluskey R. T., Schlossman S. F. Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med. 1980 Oct 1;152(4):771–782. doi: 10.1084/jem.152.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Doniach D., Roitt I. M., Walker J. G., Sherlock S. Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications. Clin Exp Immunol. 1966 Jul;1(3):237–262. [PMC free article] [PubMed] [Google Scholar]
  3. Epstein O., Thomas H. C., Sherlock S. Primary biliary cirrhosis is a dry gland syndrome with features of chronic graft-versus-host disease. Lancet. 1980 May 31;1(8179):1166–1168. doi: 10.1016/s0140-6736(80)91621-9. [DOI] [PubMed] [Google Scholar]
  4. Fox R. A., Dudley F. J., Samuels M., Milligan J., Sherlock S. Lymphocyte transformation in response to phytohaemagglutinin in primary biliary cirrhosis: the search for a plasma inhibitory factor. Gut. 1973 Feb;14(2):89–93. doi: 10.1136/gut.14.2.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fox R. A., Dudley F. J., Sherlock S. The primary immune response to haemocyanin in patients with primary biliary cirrhosis. Clin Exp Immunol. 1973 Aug;14(4):473–480. [PMC free article] [PubMed] [Google Scholar]
  6. Geubel A. P., Keller R. H., Summerskill W. H., Dickson E. R., Tomasi T. B., Shorter R. G. Lymphocyte cytotoxicity and inhibition studied with autologous liver cells: observations in chronic active liver disease and the primary biliary cirrhosis syndrome. Gastroenterology. 1976 Sep;71(3):450–456. [PubMed] [Google Scholar]
  7. Golding P. L., Smith M., Williams R. Multisystem involvement in chronic liver disease. Studies on the incidence and pathogenesis. Am J Med. 1973 Dec;55(6):772–782. doi: 10.1016/0002-9343(73)90258-1. [DOI] [PubMed] [Google Scholar]
  8. James S. P., Elson C. O., Jones E. A., Strober W. Abnormal regulation of immunoglobulin synthesis in vitro in primary biliary cirrhosis. Gastroenterology. 1980 Aug;79(2):242–254. [PubMed] [Google Scholar]
  9. Klatskin G., Kantor F. S. Mitochondrial antibody in primary biliary cirrhosis and other diseases. Ann Intern Med. 1972 Oct;77(4):533–541. doi: 10.7326/0003-4819-77-4-533. [DOI] [PubMed] [Google Scholar]
  10. McFarlane I. G., Wojcicka B. M., Tsantoulas D. C., Funk C., Portmann B., Eddleston A. L., Williams R. Cellular immune responses to salivary antigens in autoimmune liver disease with sicca syndrome. Clin Exp Immunol. 1976 Sep;25(3):389–395. [PMC free article] [PubMed] [Google Scholar]
  11. McFarlane I. G., Wojcicka B. M., Tsantoulas D. C., Portmann B. C., Eddleston A. L., Williams R. Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other chronic liver diseases. Gastroenterology. 1979 Jun;76(6):1333–1340. [PubMed] [Google Scholar]
  12. Miller J., Smith M. G., Mitchell C. G., Reed W. D., Eddleston A. L., Williams R. Cell-mediated immunity to a human liver-specific antigen in patients with active chronic hepatitis and primary biliary cirrhosis. Lancet. 1972 Aug 12;2(7772):296–297. doi: 10.1016/s0140-6736(72)92904-2. [DOI] [PubMed] [Google Scholar]
  13. Morimoto C., Reinherz E. L., Borel Y., Mantzouranis E., Steinberg A. D., Schlossman S. F. Autoantibody to an immunoregulatory inducer population in patients with juvenile rheumatoid arthritis. J Clin Invest. 1981 Mar;67(3):753–761. doi: 10.1172/JCI110092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morimoto C., Reinherz E. L., Schlossman S. F., Schur P. H., Mills J. A., Steinberg A. D. Alterations in immunoregulatory T cell subsets in active systemic lupus erythematosus. J Clin Invest. 1980 Nov;66(5):1171–1174. doi: 10.1172/JCI109948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paronetto F., Vernace S. Immunological studies in patients with chronic active hepatitis. Cytotoxic activity of lymphocytes to autochthonous liver cells grown in tissue culture. Clin Exp Immunol. 1975 Jan;19(1):99–104. [PMC free article] [PubMed] [Google Scholar]
  16. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells. J Immunol. 1979 Sep;123(3):1312–1317. [PubMed] [Google Scholar]
  18. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Further characterization of the human inducer T cell subset defined by monoclonal antibody. J Immunol. 1979 Dec;123(6):2894–2896. [PubMed] [Google Scholar]
  19. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinherz E. L., Weiner H. L., Hauser S. L., Cohen J. A., Distaso J. A., Schlossman S. F. Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies. N Engl J Med. 1980 Jul 17;303(3):125–129. doi: 10.1056/NEJM198007173030303. [DOI] [PubMed] [Google Scholar]
  21. Routhier G., Epstein O., Janossy G., Thomas H. C., Sherlock, Kung P. C., Goldstein G. Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis. Lancet. 1980 Dec 6;2(8206):1223–1226. doi: 10.1016/s0140-6736(80)92481-2. [DOI] [PubMed] [Google Scholar]
  22. Salerno F., Fargion S. R., Cappellini M. D., Fiorelli G., Dioguardi N. Rosette inhibition test in chronic liver disease. J Clin Pathol. 1976 Sep;29(9):778–781. doi: 10.1136/jcp.29.9.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sherlock S., Fox R. A., James D. G., Scheuer P. J., Sharma O. Impaired delayed hypersensitivity in primary biliary cirrhosis. Lancet. 1969 May 10;1(7602):959–962. doi: 10.1016/s0140-6736(69)91860-1. [DOI] [PubMed] [Google Scholar]
  24. Sherlock S., Scheuer P. J. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med. 1973 Sep 27;289(13):674–678. doi: 10.1056/NEJM197309272891306. [DOI] [PubMed] [Google Scholar]
  25. Thomas H. C., Freni M., Sanchez-Tapias J., de Villiers D., Jain S., Sherlock S. Peripheral blood lymphocyte populations in chronic liver disease. Clin Exp Immunol. 1976 Nov;26(2):222–227. [PMC free article] [PubMed] [Google Scholar]
  26. Thomas H. C., Holden R., Jones J. V., Peacock D. B. Immune response to phi X 174 in man. 5. Primary and secondary antibody production in primary biliary cirrhosis. Gut. 1976 Nov;17(11):844–848. doi: 10.1136/gut.17.11.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thomas H. C., Potter B. J., Sherlock S. Is primary biliary cirrhosis an immune complex disease? Lancet. 1977 Dec 17;2(8051):1261–1263. doi: 10.1016/s0140-6736(77)92666-6. [DOI] [PubMed] [Google Scholar]
  28. Thomson A. D., Cochrane M. A., McFarlane I. G., Eddleston A. L., Williams R. Lymphocyte cytotoxicity to isolated hepatocytes in chronic active hepatitis. Nature. 1974 Dec 20;252(5485):721–722. doi: 10.1038/252721a0. [DOI] [PubMed] [Google Scholar]
  29. Wands J. R., Dienstag J. L., Bhan A. K., Feller E. R., Isselbacher K. J. Circulating immune complexes and complement activation in primary biliary cirrhosis. N Engl J Med. 1978 Feb 2;298(5):233–237. doi: 10.1056/NEJM197802022980502. [DOI] [PubMed] [Google Scholar]

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

RESOURCES