Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Jan;99(1):82–89. doi: 10.1111/j.1365-2249.1995.tb03476.x

Lysis of human macrophages by cytolytic CD4+ T cells fails to affect survival of intracellular Mycobacterium bovis-bacille Calmette-Guérin (BCG).

N Fazal 1, D A Lammas 1, M Rahelu 1, A D Pithie 1, J S Gaston 1, D S Kumararatne 1
PMCID: PMC1534143  PMID: 7813114

Abstract

Human CD4+, mycobacteria-specific, cytolytic T cell clones were used to lyse BCG-infected macrophages, and the effect on the subsequent growth and viability of the organisms was examined. The survival of released bacteria following cell lysis was assessed by both 3H-uridine labelling and colony-forming unit (CFU) estimation. The results indicate that even when effective antigen-specific or lectin-mediated cytolysis of the infected macrophages was achieved, there was no evidence for a direct mycobactericidal effect on the intracellular bacteria. This remained the case even if the period of co-culture of T cells and macrophages was extended up to 48 h. Pretreatment of the macrophages with interferon-gamma (IFN-gamma) was not able to act together with T cell-mediated lysis to produce inhibition of mycobacterial growth.

Full text

PDF
87

Selected References

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

  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. Bermudez L. E. Production of transforming growth factor-beta by Mycobacterium avium-infected human macrophages is associated with unresponsiveness to IFN-gamma. J Immunol. 1993 Mar 1;150(5):1838–1845. [PubMed] [Google Scholar]
  3. De Libero G., Flesch I., Kaufmann S. H. Mycobacteria-reactive Lyt-2+ T cell lines. Eur J Immunol. 1988 Jan;18(1):59–66. doi: 10.1002/eji.1830180110. [DOI] [PubMed] [Google Scholar]
  4. Fazal N., Bartlett R., Lammas D. A., Kumararatne D. S. A comparison of the different methods available for determining BCG-macrophage interactions in vitro, including a new method of colony counting in broth. FEMS Microbiol Immunol. 1992 Dec;5(5-6):355–362. doi: 10.1111/j.1574-6968.1992.tb05921.x. [DOI] [PubMed] [Google Scholar]
  5. Flesch I., Kaufmann S. H. Mycobacterial growth inhibition by interferon-gamma-activated bone marrow macrophages and differential susceptibility among strains of Mycobacterium tuberculosis. J Immunol. 1987 Jun 15;138(12):4408–4413. [PubMed] [Google Scholar]
  6. Gaston J. S., Life P. F., Jenner P. J., Colston M. J., Bacon P. A. Recognition of a mycobacteria-specific epitope in the 65-kD heat-shock protein by synovial fluid-derived T cell clones. J Exp Med. 1990 Mar 1;171(3):831–841. doi: 10.1084/jem.171.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hancock G. E., Cohn Z. A., Kaplan G. The generation of antigen-specific, major histocompatibility complex-restricted cytotoxic T lymphocytes of the CD4+ phenotype. Enhancement by the cutaneous administration of interleukin 2. J Exp Med. 1989 Mar 1;169(3):909–919. doi: 10.1084/jem.169.3.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  9. Kaplan G., Sheftel G., Job C. K., Mathur N. K., Nath I., Cohn Z. A. Efficacy of a cell-mediated reaction to the purified protein derivative of tuberculin in the disposal of Mycobacterium leprae from human skin. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5210–5214. doi: 10.1073/pnas.85.14.5210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Kaufmann S. H. Immunity to intracellular bacteria. Annu Rev Immunol. 1993;11:129–163. doi: 10.1146/annurev.iy.11.040193.001021. [DOI] [PubMed] [Google Scholar]
  12. Kaufmann S. H., Rodewald H. R., Hug E., De Libero G. Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity. J Immunol. 1988 May 1;140(9):3173–3179. [PubMed] [Google Scholar]
  13. Kumararatne D. S., Pithie A. S., Drysdale P., Gaston J. S., Kiessling R., Iles P. B., Ellis C. J., Innes J., Wise R. Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis. Clin Exp Immunol. 1990 Jun;80(3):314–323. doi: 10.1111/j.1365-2249.1990.tb03287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lorgat F., Keraan M. M., Lukey P. T., Ress S. R. Evidence for in vivo generation of cytotoxic T cells. PPD-stimulated lymphocytes from tuberculous pleural effusions demonstrate enhanced cytotoxicity with accelerated kinetics of induction. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):418–423. doi: 10.1164/ajrccm/145.2_Pt_1.418. [DOI] [PubMed] [Google Scholar]
  15. Molloy A., Meyn P. A., Smith K. D., Kaplan G. Recognition and destruction of Bacillus Calmette-Guerin-infected human monocytes. J Exp Med. 1993 Jun 1;177(6):1691–1698. doi: 10.1084/jem.177.6.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ottenhoff T. H., Ab B. K., Van Embden J. D., Thole J. E., Kiessling R. The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette-Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes. J Exp Med. 1988 Nov 1;168(5):1947–1952. doi: 10.1084/jem.168.5.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pithie A. D., Rahelu M., Kumararatne D. S., Drysdale P., Gaston J. S., Iles P. B., Innes J. A., Ellis C. J. Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG. Thorax. 1992 Sep;47(9):695–701. doi: 10.1136/thx.47.9.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rook G. A., Champion B. R., Steele J., Varey A. M., Stanford J. L. I-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages. Clin Exp Immunol. 1985 Feb;59(2):414–420. [PMC free article] [PubMed] [Google Scholar]
  19. Silva M. T., Silva M. N., Appelberg R. Neutrophil-macrophage cooperation in the host defence against mycobacterial infections. Microb Pathog. 1989 May;6(5):369–380. doi: 10.1016/0882-4010(89)90079-x. [DOI] [PubMed] [Google Scholar]
  20. Walker L., Lowrie D. B. Killing of Mycobacterium microti by immunologically activated macrophages. Nature. 1981 Sep 3;293(5827):69–71. doi: 10.1038/293069a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES