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. 1991 Feb;59(2):684–688. doi: 10.1128/iai.59.2.684-688.1991

Mycobacterium leprae renders Schwann cells and mononuclear phagocytes susceptible or resistant to killer cells.

U Steinhoff 1, A Wand-Württenberger 1, A Bremerich 1, S H Kaufmann 1
PMCID: PMC257811  PMID: 1898912

Abstract

Acquired resistance to Mycobacterium leprae, the etiologic agent of leprosy, crucially depends on cellular immune mechanisms. In addition to interleukin-mediated helper functions, killer mechanisms seem to be involved. This study addresses the question of how M. leprae render mononuclear phagocytes and Schwann cells, its natural targets, susceptible or resistant to killer cells. Killer activities were stimulated in peripheral blood mononuclear cells from healthy individuals by incubation with mycobacteria plus interleukin-2. These cells lysed Schwann cells and mononuclear phagocytes which had been pulsed with dead M. leprae, while unpulsed targets remained virtually unaffected. Importantly, targets infected with viable M. leprae were not lysed; furthermore, infection with viable M. leprae as well as gamma interferon stimulation or heat shock caused resistance in otherwise susceptible targets which had been pulsed with dead M. leprae. Thus, M. leprae markedly influenced the effect of killer cells on Schwann cells and mononuclear phagocytes.

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Selected References

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  1. Ab B. K., Kiessling R., Van Embden J. D., Thole J. E., Kumararatne D. S., Pisa P., Wondimu A., Ottenhoff T. H. Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein. Eur J Immunol. 1990 Feb;20(2):369–377. doi: 10.1002/eji.1830200221. [DOI] [PubMed] [Google Scholar]
  2. Blanchard D. K., Michelini-Norris M. B., Friedman H., Djeu J. Y. Lysis of mycobacteria-infected monocytes by IL-2-activated killer cells: role of LFA-1. Cell Immunol. 1989 Apr 1;119(2):402–411. doi: 10.1016/0008-8749(89)90254-2. [DOI] [PubMed] [Google Scholar]
  3. Blanchard D. K., Stewart W. E., 2nd, Klein T. W., Friedman H., Djeu J. Y. Cytolytic activity of human peripheral blood leukocytes against Legionella pneumophila-infected monocytes: characterization of the effector cell and augmentation by interleukin 2. J Immunol. 1987 Jul 15;139(2):551–556. [PubMed] [Google Scholar]
  4. Buchmeier N. A., Heffron F. Induction of Salmonella stress proteins upon infection of macrophages. Science. 1990 May 11;248(4956):730–732. doi: 10.1126/science.1970672. [DOI] [PubMed] [Google Scholar]
  5. Carl M., Dasch G. A. Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors. J Immunol. 1986 Apr 1;136(7):2654–2661. [PubMed] [Google Scholar]
  6. Chiang H. L., Terlecky S. R., Plant C. P., Dice J. F. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science. 1989 Oct 20;246(4928):382–385. doi: 10.1126/science.2799391. [DOI] [PubMed] [Google Scholar]
  7. Chiplunkar S., De Libero G., Kaufmann S. H. Mycobacterium leprae-specific Lyt-2+ T lymphocytes with cytolytic activity. Infect Immun. 1986 Dec;54(3):793–797. doi: 10.1128/iai.54.3.793-797.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clerget M., Polla B. S. Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1081–1085. doi: 10.1073/pnas.87.3.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gromkowski S. H., Yagi J., Janeway C. A., Jr Elevated temperature regulates tumor necrosis factor-mediated immune killing. Eur J Immunol. 1989 Sep;19(9):1709–1714. doi: 10.1002/eji.1830190927. [DOI] [PubMed] [Google Scholar]
  10. Holm G., Perlmann P. Cytotoxic potential of stimulated human lymphocytes. J Exp Med. 1967 Apr 1;125(4):721–736. doi: 10.1084/jem.125.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jättelä M. Effects of heat shock on cytolysis mediated by NK cells, LAK cells, activated monocytes and TNFs alpha and beta. Scand J Immunol. 1990 Feb;31(2):175–182. doi: 10.1111/j.1365-3083.1990.tb02757.x. [DOI] [PubMed] [Google Scholar]
  12. Jättelä M., Saksela K., Saksela E. Heat shock protects WEHI-164 target cells from the cytolysis by tumor necrosis factors alpha and beta. Eur J Immunol. 1989 Aug;19(8):1413–1417. doi: 10.1002/eji.1830190810. [DOI] [PubMed] [Google Scholar]
  13. Kaplan G., Kiessling R., Teklemariam S., Hancock G., Sheftel G., Job C. K., Converse P., Ottenhoff T. H., Becx-Bleumink M., Dietz M. The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2. J Exp Med. 1989 Mar 1;169(3):893–907. doi: 10.1084/jem.169.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaplan G., Laal S., Sheftel G., Nusrat A., Nath I., Mathur N. K., Mishra R. S., Cohn Z. A. The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients. J Exp Med. 1988 Nov 1;168(5):1811–1824. doi: 10.1084/jem.168.5.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kaufmann S. H. CD8+ T lymphocytes in intracellular microbial infections. Immunol Today. 1988 Jun;9(6):168–174. doi: 10.1016/0167-5699(88)91292-3. [DOI] [PubMed] [Google Scholar]
  16. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  17. Kaufmann S. H. Immunity against intracellular bacteria: biological effector functions and antigen specificity of T lymphocytes. Curr Top Microbiol Immunol. 1988;138:141–176. [PubMed] [Google Scholar]
  18. Kaufmann S. H. Immunology of leprosy: new findings, future perspectives. Microb Pathog. 1986 Apr;1(2):107–114. doi: 10.1016/0882-4010(86)90013-6. [DOI] [PubMed] [Google Scholar]
  19. Klimpel G. R., Niesel D. W., Klimpel K. D. Natural cytotoxic effector cell activity against Shigella flexneri-infected HeLa cells. J Immunol. 1986 Feb 1;136(3):1081–1086. [PubMed] [Google Scholar]
  20. Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
  21. Mor N. Intracellular location of Mycobacterium leprae in macrophages of normal and immune-deficient mice and effect of rifampin. Infect Immun. 1983 Nov;42(2):802–811. doi: 10.1128/iai.42.2.802-811.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Munk M. E., Gatrill A. J., Kaufmann S. H. Target cell lysis and IL-2 secretion by gamma/delta T lymphocytes after activation with bacteria. J Immunol. 1990 Oct 15;145(8):2434–2439. [PubMed] [Google Scholar]
  23. Munk M. E., Schoel B., Modrow S., Karr R. W., Young R. A., Kaufmann S. H. T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein. J Immunol. 1989 Nov 1;143(9):2844–2849. [PubMed] [Google Scholar]
  24. Pelc S., Gompel C., Simonet M. L. S-100 protein expression in satellite and Schwann cells in neuroblastoma. An immunohistochemical and ultrastructural study. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;51(6):487–495. doi: 10.1007/BF02899054. [DOI] [PubMed] [Google Scholar]
  25. Renkonen R., Ristimäki A., Häyry P. Interferon-gamma protects human endothelial cells from lymphokine-activated killer cell-mediated lysis. Eur J Immunol. 1988 Nov;18(11):1839–1842. doi: 10.1002/eji.1830181129. [DOI] [PubMed] [Google Scholar]
  26. Resnick M., Roguel N., Bercovier H., Enk C., Frankenburg S., Kedar E. Lysis of murine macrophages infected with intracellular pathogens by interleukin 2-activated killer (LAK) cells in vitro. Cell Immunol. 1988 Apr 15;113(1):214–219. doi: 10.1016/0008-8749(88)90019-6. [DOI] [PubMed] [Google Scholar]
  27. Steinhoff U., Kaufmann S. H. Specific lysis by CD8+ T cells of Schwann cells expressing Mycobacterium leprae antigens. Eur J Immunol. 1988 Jun;18(6):969–972. doi: 10.1002/eji.1830180622. [DOI] [PubMed] [Google Scholar]
  28. Steinhoff U., Schoel B., Kaufmann S. H. Lysis of interferon-gamma activated Schwann cell by cross-reactive CD8+ alpha/beta T cells with specificity for the mycobacterial 65 kd heat shock protein. Int Immunol. 1990;2(3):279–284. doi: 10.1093/intimm/2.3.279. [DOI] [PubMed] [Google Scholar]
  29. Young R. A. Stress proteins and immunology. Annu Rev Immunol. 1990;8:401–420. doi: 10.1146/annurev.iy.08.040190.002153. [DOI] [PubMed] [Google Scholar]

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