Skip to main content
Log in

Functional analysis of peripheral blood lymphocytes isolated from patients with chronic hepatitis type B

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Cell-mediated immunity, evaluated by lymphocyte proliferation and expression of the activation antigen interleukin-2 receptor in response to mitogens such as phytohemagglutinin and concanavalin-A, has been reported to be defective in chronic hepatitis B virus carriers. However, no definite conclusion on the functional state of T cells from these patients can be drawn. In the present study, we have investigated the expression of a wide set of lymphoid activation molecules as well as the proliferative response of peripheral blood lymphocytes isolated from patients with chronic hepatitis type B afterin vitro stimulation with monoclonal antibodies to both the T-cell receptor-CD3 complex and the CD2 molecule, which are the two main T-cell activation pathways. Our findings show that peripheral T lymphocytes from patients with chronic hepatitis type B express the activation antigens 4F2 molecule, interleukin-2 receptor, and activation inducer molecule (AIM) antigen, and proliferate normally after specific stimulation through either the T-cell receptor-CD3 complex or the CD2 molecule. These results suggest that the peripheral blood T cells of patients with chronic hepatitis B are fully operative and functionally competentin vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. García-Monzón C, Moreno-Otero R, Pajares JM, García-Sánchez A, López-Botet M, de Landázuri MO, Sánchez-Madrid F: Expression of a novel activation antigen on intrahepatic CD8+ T lymphocytes in viral chronic active hepatitis. Gastroenterology 98:1029–1035, 1990

    Google Scholar 

  2. Thomas HC: Immunologic aspects of liver disease.In Diseases of the Liver. L. Schiff and ER Schiff (eds). JB Lippincott, Philadelphia, 1987, pp 164–167

    Google Scholar 

  3. Giustino V, Dudley FJ, Sherlock S: Thymus-dependent lymphocyte function in patients with hepatitis associated antigen. Lancet 2:850–854, 1972

    Google Scholar 

  4. Yoshioka K, Kakumu S, Murakami H, Fukui K. Interleukin-2 activity in chronic active liver diseases: Response by T cell and in the autologous mixed lymphocyte reaction. Clin Exp Immunol 56:669–676, 1984

    Google Scholar 

  5. Hanson RG, Hoofnagle JH, Minuk GY, Purcell RH, Gerin JL: Cell-mediated immunity to hepatitis B surface antigen in man. Clin Exp Immunol 57:257–262, 1984

    Google Scholar 

  6. International Group: Acute and chronic hepatitis revisited. Lancet 2:914–919, 1977

    Google Scholar 

  7. Brottier P, Boumsell L, Gelin C, Bernard A: T cell activation via CD2 (Tgp 50) molecules: Accessory cells are required to trigger T cell activation via CD2-D66 plus CD2 9.6/T11.1 epitopes. J Immunol 135:1624–1631, 1985

    Google Scholar 

  8. Spits H, Yssel H, Leeuwenberg J, De Vries JE: Antigenspecific cytotoxic T cell and antigen-specific proliferation T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. J Immunol 15:88–93, 1985

    Google Scholar 

  9. Sánchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff, Springer TA: Three-distinct antigens associated with human T lymphocyte-mediated cytolysis LFA-1, LFA-2 and LFA-3. Proc Natl Acad Sci USA 79:7489–7495, 1982

    Google Scholar 

  10. Carrera AC, Sánchez-Madrid F, López-Botet M, Bernabeu C, de Landázuri MO: Involvement of the CD4 molecule in a postactivation event on T cell proliferation. Eur J Immunol 17:179–186, 1987

    Google Scholar 

  11. Malissen B, Reboi N, Liabeuf A, Mowas C: Human cytotoxic T cell structures associated with expression of cytolysis. I. Analysis at the clonal level of the cytolysis-inhibiting effect of 7 monoclonal antibodies. Eur J Immunol 12:739–745, 1982

    Google Scholar 

  12. Hemler ME, Strominger JL: Characterization of the antigen recognized by the monoclonal antibody (4F2): Different molecular forms on human T and B lymphoblastoid cell lines. J Immunol 129:623–628, 1982

    Google Scholar 

  13. López-Botet M, Moretta A, Lowenthal J, Acolla R, Pantaleo G, Moretta L: Characterization of monoclonal antibodies directed against the human interleukin-2 receptor. Immunología 5:46–50, 1986

    Google Scholar 

  14. Cebrián M, Yagüe E, Rincón M, López-Botet, de Landázuri MO, Sánchez-Madrid F. Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. J Exp Med 168:1621–1637, 1988

    Google Scholar 

  15. López-Botet M, Moretta L: Functional characterization of human thymocytes: a limiting dilution analysis of precursors with proliferative and cytolytic activities. J Immunol 134:2299–2304, 1988

    Google Scholar 

  16. Anastassakos CH, Alexander GJM, Wolstencroft RA, Dumonde DC, Eddleston ALWF, Williams R: Failure of exogenous interleukin 1 and interleukin 2 to correct decreased lymphocyte transformation in chronic hepatitis B virus carriers. Clin Exp Immunol 68:15–22, 1987

    Google Scholar 

  17. Nouri-Aria KT, Alexander GJM, Magrin S, Anderson MG, Eddleston ALWF, Williams R: Differential effect of α-interferon on CD4 and CD8 positive lymphocytes in chronic hepatitis B virus carriers. J Hepatol 7:1–6, 1988

    Google Scholar 

  18. Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL: Clonotypic structures involved in antigen specific human T cell function. J Exp Med 157:705–719, 1983

    Google Scholar 

  19. Meuer SC, Hussey RE, Fabby M, Fox D, Acuto O, Fitzgerald KA, Hodgdon JC, Protentis JP, Schlossman SF, Reinherz EL: An alternative pathway of T cell activation: A functional role for the 50 Kda T11 sheep erythrocyte receptor protein. Cell 36:897–906, 1984

    Google Scholar 

  20. Michalak M, Quackenbush EJ, Letarte M: Inhibition of Na+/Ca++ exchanger activity in cardiac skeletal muscle sarcolemmal vesicles by monoclonal antibody 44D7. J Biol Chem 261:92–97, 1986

    Google Scholar 

  21. Pontisso P, Poon MC, Tiollais P, Brechot C: Detection of hepatitis B virus DNA in mononuclear blood cells. Br Med J 288:1563–1566, 1984

    Google Scholar 

  22. Pasquinelli C, Lauré F, Chatenoud L, Beaurin G, Gazengel C, Bismuth H, Degos F, Tiollais P, Bach JF, Brechot C: Hepatitis B virus DNA in mononuclear blood cells: A frequent event in hepatitis B surface antigen-positive and negative patients with acute and chronic liver disease. J Hepatol 3:95–103, 1986

    Google Scholar 

  23. Lauré F, Chatenoud L, Pasquinelli C, Gazengel C, Beaurin G, Torchet MF, Zagury D, Bach JF, Brechot C: Frequent lymphocytes infection by hepatitis B virus in haemophiliacs. Br J Haematol 65:181–185, 1987

    Google Scholar 

  24. Bartolomé J, Moraleda G, Molina J, Domínguez F, Porres JC, Carreño V: Hepatitis B virus DNA in liver and peripheral blood mononuclear cells during reduction in virus replication. Gastroenterology 99:1745–1750, 1990

    Google Scholar 

  25. Davison F, Alexander GJM, Anastassakos CH, Fagan EA, Williams R: Leucocyte hepatitis B virus DNA in acute and chronic hepatitis B virus infection. J Med Virol 22:379–385, 1987

    Google Scholar 

  26. Shen HD, Choo KB, Lee SD, Tsai YT, Han SH: Hepatitis B virus DNA in leukocytes of patients with hepatitis B virusassociated liver diseases. J Med Virol 18:201–211, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported in part by a grant from the INSALUD (FISS 89/0068).

Rights and permissions

Reprints and permissions

About this article

Cite this article

García-Monzón, C., Moreno-Otero, R., García-Buey, L. et al. Functional analysis of peripheral blood lymphocytes isolated from patients with chronic hepatitis type B. Digest Dis Sci 37, 73–78 (1992). https://doi.org/10.1007/BF01308345

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01308345

Key Words

Navigation