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. 1989 Nov;68(3):353–358.

Suppress of the increase in free cytosolic calcium during the inhibition of T-cell activation by an autoantibody present in the serum of leprosy patients.

T A Poulton 1, A Gallagher 1, J S Beck 1
PMCID: PMC1385447  PMID: 2592010

Abstract

A serum factor, believed to be an IgG autoantibody, in certain patients with lepromatous leprosy inhibits the proliferation of mitogen-stimulated lymphocytes. To investigate which stage of the cell cycle was inhibited, we examined the effect of these sera on the kinetics of lymphocyte activation induced by several mitogenic agents: phytohaemagglutinin (PHA), the calcium ionophore A23187, the phorbol ester phorbol myristate acetate (PMA) and purified protein derivative of BCG (PPD). Seven out of 54 sera tested were found to inhibit PHA-stimulated proliferation. Inhibitory sera and to a lesser extent serum IgG from leprosy patients were capable of suppressing the increase in free cytosolic calcium normally observed immediately after PHA stimulation. Subsequent stages of the cell cycle, increase in cell size, the expression of the IL-2 receptor and increase in DNA were also suppressed. The inhibitory sera was not toxic and, if addition of the sera was delayed, would not inhibit lymphocytes that had already entered the cell cycle. Using mitogenic agents which act intracellularly, the normal early increase in cell size with A23187- and PMA-stimulated lymphocytes was not affected by inhibitory leprosy sera or serum IgG, but all subsequent steps in the cell cycle were suppressed; although the inhibition of proliferation in PMA-stimulated cultures was incomplete. The mechanism of action of the inhibitory sera and derived IgG, although acting through a cell surface antigen, appears to interfere with a fundamental process in activation since the effect was seen with all of the diverse stimuli examined in this study.

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Selected References

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  1. Bloom B. R., Mehra V. Immunological unresponsiveness in leprosy. Immunol Rev. 1984 Aug;80:5–28. doi: 10.1111/j.1600-065x.1984.tb00493.x. [DOI] [PubMed] [Google Scholar]
  2. Brown R. A., Kelk J., Beck J. S. The use of a microcomputer to analyse differences between histograms derived from flow cytofluorimetric measurements. Int J Biomed Comput. 1988 May-Jun;22(3-4):285–293. doi: 10.1016/0020-7101(88)90083-9. [DOI] [PubMed] [Google Scholar]
  3. Darzynkiewicz Z., Traganos F., Sharpless T., Melamed M. R. Lymphocyte stimulation: a rapid multiparameter analysis. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2881–2884. doi: 10.1073/pnas.73.8.2881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Geller R. L., Gromo G., Inverardi L., Ferrero E., Bach F. H. Stepwise activation of T cells. Role of the calcium ionophore A23187. J Immunol. 1987 Dec 15;139(12):3930–3934. [PubMed] [Google Scholar]
  5. Gibbs J. H., Brown R. A., Robertson A. J., Potts R. C., Beck J. S. A new method of testing for mitogen-induced lymphocyte stimulation: measurement of the percentage of growing cells and of some aspects of their cell kinetics with an electronic particle counter. J Immunol Methods. 1979;25(2):147–158. doi: 10.1016/0022-1759(79)90050-4. [DOI] [PubMed] [Google Scholar]
  6. Hara T., Fu S. M. Human T cell activation. I. Monocyte-independent activation and proliferation induced by anti-T3 monoclonal antibodies in the presence of tumor promoter 12-o-tetradecanoyl phorbol-13 acetate. J Exp Med. 1985 Apr 1;161(4):641–656. doi: 10.1084/jem.161.4.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haregewoin A., Godal T., Mustafa A. S., Belehu A., Yemaneberhan T. T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy. Nature. 1983 May 26;303(5915):342–344. doi: 10.1038/303342a0. [DOI] [PubMed] [Google Scholar]
  8. Hooton J. W., Gibbs C., Paetkau V. Interaction of interleukin 2 with cells: quantitative analysis of effects. J Immunol. 1985 Oct;135(4):2464–2473. [PubMed] [Google Scholar]
  9. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Imboden J. B., Weiss A., Stobo J. D. The antigen receptor on a human T cell line initiates activation by increasing cytoplasmic free calcium. J Immunol. 1985 Feb;134(2):663–665. [PubMed] [Google Scholar]
  11. Kuno M., Gardner P. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes. Nature. 1987 Mar 19;326(6110):301–304. doi: 10.1038/326301a0. [DOI] [PubMed] [Google Scholar]
  12. Manger B., Weiss A., Imboden J., Laing T., Stobo J. D. The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex. Effects of stimulation with soluble or immobilized CD3 antibodies. J Immunol. 1987 Oct 15;139(8):2755–2760. [PubMed] [Google Scholar]
  13. Minota S., Winfield J. B. IgG anti-lymphocyte antibodies in systemic lupus erythematosus react with surface molecules shared by peripheral T cells and a primitive T cell line. J Immunol. 1987 Mar 15;138(6):1750–1756. [PubMed] [Google Scholar]
  14. Mohagheghpour N., Gelber R. R., Engleman E. G. T cell defect in lepromatous leprosy is reversible in vitro in the absence of exogenous growth factors. J Immunol. 1987 Jan 15;138(2):570–574. [PubMed] [Google Scholar]
  15. Nath I., Curtis J., Sharma A. K., Talwar G. P. Circulating T-cell numbers and their mitogenic potential in leprosy--correlation with mycobacterial load. Clin Exp Immunol. 1977 Sep;29(3):393–400. [PMC free article] [PubMed] [Google Scholar]
  16. Nelson D. S., Penrose J. M., Waters M. F., Pearson J. M., Nelson M. Depressive effect of serum from patients with leprosy on mixed lymphocyte reactions. Influence of anti-leprosy treatment. Clin Exp Immunol. 1975 Dec;22(3):385–392. [PMC free article] [PubMed] [Google Scholar]
  17. Nelson D. S., Penrose J. M., Waters M. F., Pearson J. M., Nelson M. Depressive effect of serum from patients with leprosy on mixed lymphocyte reactions. Influence of anti-leprosy treatment. Clin Exp Immunol. 1975 Dec;22(3):385–392. [PMC free article] [PubMed] [Google Scholar]
  18. Nisbet-Brown E., Cheung R. K., Lee J. W., Gelfand E. W. Antigen-dependent increase in cytosolic free calcium in specific human T-lymphocyte clones. Nature. 1985 Aug 8;316(6028):545–547. doi: 10.1038/316545a0. [DOI] [PubMed] [Google Scholar]
  19. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  20. O'Flynn K., Zanders E. D., Lamb J. R., Beverley P. C., Wallace D. L., Tatham P. E., Tax W. J., Linch D. C. Investigation of early T cell activation: analysis of the effect of specific antigen, interleukin 2 and monoclonal antibodies on intracellular free calcium concentration. Eur J Immunol. 1985 Jan;15(1):7–11. doi: 10.1002/eji.1830150103. [DOI] [PubMed] [Google Scholar]
  21. Poulton T. A., Gallagher A., Potts R. C., Beck J. S. Changes in activation markers and cell membrane receptors on human peripheral blood T lymphocytes during cell cycle progression after PHA stimulation. Immunology. 1988 Jul;64(3):419–425. [PMC free article] [PubMed] [Google Scholar]
  22. Salgame P. R., Mahadevan P. R., Antia N. H. Mechanism of immunosuppression in leprosy: presence of suppressor factor(s) from macrophages of lepromatous patients. Infect Immun. 1983 Jun;40(3):1119–1126. doi: 10.1128/iai.40.3.1119-1126.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sinclair W. K., Ross D. W. Modesl of growth in mammalian cells. Biophys J. 1969 Aug;9(8):1056–1070. doi: 10.1016/s0006-3495(69)86436-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sussman J. J., Merćep M., Saito T., Germain R. N., Bonvini E., Ashwell J. D. Dissociation of phosphoinositide hydrolysis and Ca2+ fluxes from the biological responses of a T-cell hybridoma. Nature. 1988 Aug 18;334(6183):625–628. doi: 10.1038/334625a0. [DOI] [PubMed] [Google Scholar]

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