Skip to main content
PMC home page
Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1997 Jan;4(1):14–18. doi: 10.1128/cdli.4.1.14-18.1997

Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis.

R Duarte 1, J M Kindlelán 1, J Carracedo 1, P Sánchez-Guijo 1, R Ramírez 1
PMCID: PMC170469  PMID: 9008275

Abstract

Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that resembles that of superantigens from alpha/beta T cells. After culture in vitro with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T lymphocytes from ACF-TBC patients occurs in a range similar to that observed in healthy subjects. Following activation, H37Ra-stimulated gamma/delta T lymphocytes from healthy subjects did proliferate in the presence of exogenous recombinant human interleukin 2. However, under the same conditions, gamma/delta T lymphocytes from ACF-TBC patients not only did not proliferate but died by apoptosis. These results suggest that in gamma/delta T lymphocytes from patients with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads to apoptotic cell death.

Full Text

The Full Text of this article is available as a PDF (205.2 KB).

Selected References

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

  1. Agostini C., Zambello R., Trentin L., Cerutti A., Bulian P., Crivellaro C., Cipriani A., Semenzato G. Gamma delta T cell receptor subsets in the lung of patients with HIV-1 infection. Cell Immunol. 1994 Jan;153(1):194–205. doi: 10.1006/cimm.1994.1017. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. F., Grisso C. L., Abrams J. S., Band H., Rea T. H., Modlin R. L. Gamma delta T lymphocytes in human tuberculosis. J Infect Dis. 1992 Mar;165(3):506–512. doi: 10.1093/infdis/165.3.506. [DOI] [PubMed] [Google Scholar]
  3. Boom W. H., Chervenak K. A., Mincek M. A., Ellner J. J. Role of the mononuclear phagocyte as an antigen-presenting cell for human gamma delta T cells activated by live Mycobacterium tuberculosis. Infect Immun. 1992 Sep;60(9):3480–3488. doi: 10.1128/iai.60.9.3480-3488.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Constant P., Davodeau F., Peyrat M. A., Poquet Y., Puzo G., Bonneville M., Fournié J. J. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994 Apr 8;264(5156):267–270. doi: 10.1126/science.8146660. [DOI] [PubMed] [Google Scholar]
  5. Crispe N. Mechanisms of self-tolerance. Immunol Today. 1988 Nov;9(11):329–331. doi: 10.1016/0167-5699(88)91329-1. [DOI] [PubMed] [Google Scholar]
  6. Dannecker G., Mecheri S., Staiano-Coico L., Hoffmann M. K. A characteristic Mls-1a response precedes Mls-1a anergy in vivo. J Immunol. 1991 Apr 1;146(7):2083–2087. [PubMed] [Google Scholar]
  7. De Libero G., Casorati G., Giachino C., Carbonara C., Migone N., Matzinger P., Lanzavecchia A. Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells. J Exp Med. 1991 Jun 1;173(6):1311–1322. doi: 10.1084/jem.173.6.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drake C. G., Kotzin B. L. Superantigens: biology, immunology, and potential role in disease. J Clin Immunol. 1992 May;12(3):149–162. doi: 10.1007/BF00918083. [DOI] [PubMed] [Google Scholar]
  9. Gambón-Deza F., Pacheco Carracedo M., Cerdá Mota T., Montes Santiago J. Lymphocyte populations during tuberculosis infection: V beta repertoires. Infect Immun. 1995 Apr;63(4):1235–1240. doi: 10.1128/iai.63.4.1235-1240.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Groh V., Porcelli S., Fabbi M., Lanier L. L., Picker L. J., Anderson T., Warnke R. A., Bhan A. K., Strominger J. L., Brenner M. B. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 1;169(4):1277–1294. doi: 10.1084/jem.169.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
  12. Havlir D. V., Ellner J. J., Chervenak K. A., Boom W. H. Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis. J Clin Invest. 1991 Feb;87(2):729–733. doi: 10.1172/JCI115053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hochstenbach F., Brenner M. B. Newly identified gamma delta and beta delta T-cell receptors. J Clin Immunol. 1990 Jan;10(1):1–18. doi: 10.1007/BF00917493. [DOI] [PubMed] [Google Scholar]
  14. Ignatowicz L., Kappler J., Marrack P. The effects of chronic infection with a superantigen-producing virus. J Exp Med. 1992 Apr 1;175(4):917–923. doi: 10.1084/jem.175.4.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ito M., Kojiro N., Ikeda T., Ito T., Funada J., Kokubu T. Increased proportions of peripheral blood gamma delta T cells in patients with pulmonary tuberculosis. Chest. 1992 Jul;102(1):195–197. doi: 10.1378/chest.102.1.195. [DOI] [PubMed] [Google Scholar]
  16. Jouvin-Marche E., Cazenave P. A., Voegtle D., Marche P. N. V beta 17 T-cell deletion by endogenous mammary tumor virus in wild-type-derived mouse strain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3232–3235. doi: 10.1073/pnas.89.8.3232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kabelitz D., Bender A., Prospero T., Wesselborg S., Janssen O., Pechhold K. The primary response of human gamma/delta + T cells to Mycobacterium tuberculosis is restricted to V gamma 9-bearing cells. J Exp Med. 1991 Jun 1;173(6):1331–1338. doi: 10.1084/jem.173.6.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ladel C. H., Hess J., Daugelat S., Mombaerts P., Tonegawa S., Kaufmann S. H. Contribution of alpha/beta and gamma/delta T lymphocytes to immunity against Mycobacterium bovis bacillus Calmette Guérin: studies with T cell receptor-deficient mutant mice. Eur J Immunol. 1995 Mar;25(3):838–846. doi: 10.1002/eji.1830250331. [DOI] [PubMed] [Google Scholar]
  19. Lyons A. B., Samuel K., Sanderson A., Maddy A. H. Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry. Cytometry. 1992;13(8):809–821. doi: 10.1002/cyto.990130803. [DOI] [PubMed] [Google Scholar]
  20. Ohmen J. D., Barnes P. F., Uyemura K., Lu S. Z., Grisso C. L., Modlin R. L. The T cell receptors of human gamma delta T cells reactive to Mycobacterium tuberculosis are encoded by specific V genes but diverse V-J junctions. J Immunol. 1991 Nov 15;147(10):3353–3359. [PubMed] [Google Scholar]
  21. Panchamoorthy G., McLean J., Modlin R. L., Morita C. T., Ishikawa S., Brenner M. B., Band H. A predominance of the T cell receptor V gamma 2/V delta 2 subset in human mycobacteria-responsive T cells suggests germline gene encoded recognition. J Immunol. 1991 Nov 15;147(10):3360–3369. [PubMed] [Google Scholar]
  22. Pfeffer K., Schoel B., Plesnila N., Lipford G. B., Kromer S., Deusch K., Wagner H. A lectin-binding, protease-resistant mycobacterial ligand specifically activates V gamma 9+ human gamma delta T cells. J Immunol. 1992 Jan 15;148(2):575–583. [PubMed] [Google Scholar]
  23. Scott P., Kaufmann S. H. The role of T-cell subsets and cytokines in the regulation of infection. Immunol Today. 1991 Oct;12(10):346–348. doi: 10.1016/0167-5699(91)90063-Y. [DOI] [PubMed] [Google Scholar]
  24. Sperling A. I., Linsley P. S., Barrett T. A., Bluestone J. A. CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes. J Immunol. 1993 Dec 1;151(11):6043–6050. [PubMed] [Google Scholar]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES