Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Oct;83(19):7457–7461. doi: 10.1073/pnas.83.19.7457

Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity.

L Chatenoud, B Dugas, G Beaurain, M Touam, T Drueke, A Vasquez, P Galanaud, J F Bach, J F Delfraissy
PMCID: PMC386737  PMID: 3094009

Abstract

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.

Full text

PDF

Selected References

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

  1. Ambrus J. L., Jr, Fauci A. S. Human B lymphoma cell line producing B cell growth factor. J Clin Invest. 1985 Feb;75(2):732–739. doi: 10.1172/JCI111754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Butler J. L., Muraguchi A., Lane H. C., Fauci A. S. Development of a human T-T cell hybridoma secreting B cell growth factor. J Exp Med. 1983 Jan 1;157(1):60–68. doi: 10.1084/jem.157.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chatenoud L., Bach M. A. Abnormalities of T-cell subsets in glomerulonephritis and systemic lupus erythematosus. Kidney Int. 1981 Aug;20(2):267–274. doi: 10.1038/ki.1981.130. [DOI] [PubMed] [Google Scholar]
  5. Chouaib S., Fradelizi D. The mechanism of inhibition of human IL 2 production. J Immunol. 1982 Dec;129(6):2463–2468. [PubMed] [Google Scholar]
  6. Crosnier J., Jungers P., Couroucé A. M., Laplanche A., Benhamou E., Degos F., Lacour B., Prunet P., Cerisier Y., Guesry P. Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients. Lancet. 1981 Apr 11;1(8224):797–800. doi: 10.1016/s0140-6736(81)92679-9. [DOI] [PubMed] [Google Scholar]
  7. DAMMIN G. J., COUCH N. P., MURRAY J. E. Prolonged survival of skin homografts in uremic patients. Ann N Y Acad Sci. 1957 Mar 22;64(5):967–976. doi: 10.1111/j.1749-6632.1957.tb52488.x. [DOI] [PubMed] [Google Scholar]
  8. Dugas B., Vazquez A., Geŕard J. P., Richard Y., Auffredou M. T., Delfraissy J. F., Fradelizi D., Galanaud P. Functional properties of two human B cell growth factor species separated by lectin affinity column. J Immunol. 1985 Jul;135(1):333–338. [PubMed] [Google Scholar]
  9. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huber H., Pastner D., Dittrich P., Braunsteiner H. In vitro reactivity of human lymphocytes in uraemia--a comparison with the impairment of delayed hypersensitivity. Clin Exp Immunol. 1969 Jul;5(1):75–82. [PMC free article] [PubMed] [Google Scholar]
  11. Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
  12. Lortan J. E., Kiepiela P., Coovadia H. M., Seedat Y. K. Suppressor cells assayed by numerical and functional tests in chronic renal failure. Kidney Int. 1982 Aug;22(2):192–197. doi: 10.1038/ki.1982.152. [DOI] [PubMed] [Google Scholar]
  13. Lotze M. T., Grimm E. A., Mazumder A., Strausser J. L., Rosenberg S. A. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981 Nov;41(11 Pt 1):4420–4425. [PubMed] [Google Scholar]
  14. Maizel A., Sahasrabuddhe C., Mehta S., Morgan J., Lachman L., Ford R. Biochemical separation of a human B cell mitogenic factor. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5998–6002. doi: 10.1073/pnas.79.19.5998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Muraguchi A., Butler J. L., Kehrl J. H., Fauci A. S. Differential sensitivity of human B cell subsets to activation signals delivered by anti-mu antibody and proliferative signals delivered by a monoclonal B cell growth factor. J Exp Med. 1983 Feb 1;157(2):530–546. doi: 10.1084/jem.157.2.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muraguchi A., Kasahara T., Oppenheim J. J., Fauci A. S. B cell growth factor and T cell growth factor produced by mitogen-stimulated normal human peripheral blood T lymphocytes are distinct molecules. J Immunol. 1982 Dec;129(6):2486–2489. [PubMed] [Google Scholar]
  17. Muraguchi A., Kehrl J. H., Longo D. L., Volkman D. J., Smith K. A., Fauci A. S. Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function. J Exp Med. 1985 Jan 1;161(1):181–197. doi: 10.1084/jem.161.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Okada M., Sakaguchi N., Yoshimura N., Hara H., Shimizu K., Yoshida N., Yoshizaki K., Kishimoto S., Yamamura Y., Kishimoto T. B cell growth factors and B cell differentiation factor from human T hybridomas. Two distinct kinds of B cell growth factor and their synergism in B cell proliferation. J Exp Med. 1983 Feb 1;157(2):583–590. doi: 10.1084/jem.157.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Raska K., Jr, Raskova J., Shea S. M., Frankel R. M., Wood R. H., Lifter J., Ghobrial I., Eisinger R. P., Homer L. T cell subsets and cellular immunity in end-stage renal disease. Am J Med. 1983 Nov;75(5):734–740. doi: 10.1016/0002-9343(83)90401-1. [DOI] [PubMed] [Google Scholar]
  20. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  21. Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
  22. Taniguchi T., Matsui H., Fujita T., Takaoka C., Kashima N., Yoshimoto R., Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983 Mar 24;302(5906):305–310. doi: 10.1038/302305a0. [DOI] [PubMed] [Google Scholar]
  23. Tsudo M., Uchiyama T., Uchino H. Expression of Tac antigen on activated normal human B cells. J Exp Med. 1984 Aug 1;160(2):612–617. doi: 10.1084/jem.160.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Uchiyama T., Broder S., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol. 1981 Apr;126(4):1393–1397. [PubMed] [Google Scholar]
  25. Vane J. R. The release and fate of vaso-active hormones in the circulation. Br J Pharmacol. 1969 Feb;35(2):209–242. doi: 10.1111/j.1476-5381.1969.tb07982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Watson J., Mochizuki D. Interleukin 2: a class of T cell growth factors. Immunol Rev. 1980;51:257–278. doi: 10.1111/j.1600-065x.1980.tb00324.x. [DOI] [PubMed] [Google Scholar]
  27. Yoshizaki K., Nakagawa T., Fukunaga K., Kaieda T., Maruyama S., Kishimoto S., Yamamura Y., Kishimoto T. Characterization of human B cell growth factor (BCGF) from cloned T cells or mitogen-stimulated T cells. J Immunol. 1983 Mar;130(3):1241–1246. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES