Abstract
The mycobacterial antigens stimulating human gamma delta T lymphocytes (R. L. Modlin, C. Permitz, F. M. Hofman, V. Torigian, K. Uemura, T. H. Rea, B. R. Bloom, and M. B. Brenner, Nature (London) 339:544-548, 1989; D. H. Raulet, Annu. Rev. Immunol. 7:175-207, 1989) have been characterized recently in Mycobacterium tuberculosis H37Rv as a group of four structurally related nucleotidic or phosphorylated molecules, termed TUBag1 to -4 (tuberculous antigens 1 to 4) (P. Constant, F. Davodeau, M. A. Peyrat, Y. Poquet, G. Puzo, M. Bonneville, and J. J. Fournie, Science 264:267-270, 1994). Here, we analyzed their distribution in different mycobacterial species of the M. tuberculosis group, with special emphasis on the human vaccine Mycobacterium bovis BCG. We show that the same four TUBag1 to -4 molecules are shared by these mycobacteria. Quantitative comparison reveals, however, that while the pathogen M. bovis and M. tuberculosis species produce rather high amounts of TUBag, all of the BCG strains have a surprisingly reduced production of TUBag. These observations suggest that among tuberculous mycobacteria, the bacterial TUBag load could, to some extent, constitute an immunological determinant of mycobacterial virulence for humans.
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- 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]
- Bender A., Heckl-Ostreicher B., Grondal E. J., Kabelitz D. Clonal specificity of human gamma delta T cells: V gamma 9+ T-cell clones frequently recognize Plasmodium falciparum merozoites, Mycobacterium tuberculosis, and group-A streptococci. Int Arch Allergy Immunol. 1993;100(1):12–18. doi: 10.1159/000236381. [DOI] [PubMed] [Google Scholar]
- Casorati G., De Libero G., Lanzavecchia A., Migone N. Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood. J Exp Med. 1989 Nov 1;170(5):1521–1535. doi: 10.1084/jem.170.5.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Davodeau F., Houde I., Boulot G., Romagné F., Necker A., Canavo N., Peyrat M. A., Hallet M. M., Vié H., Jacques Y. Secretion of disulfide-linked human T-cell receptor gamma delta heterodimers. J Biol Chem. 1993 Jul 25;268(21):15455–15460. [PubMed] [Google Scholar]
- Davodeau F., Peyrat M. A., Hallet M. M., Gaschet J., Houde I., Vivien R., Vie H., Bonneville M. Close correlation between Daudi and mycobacterial antigen recognition by human gamma delta T cells and expression of V9JPC1 gamma/V2DJC delta-encoded T cell receptors. J Immunol. 1993 Aug 1;151(3):1214–1223. [PubMed] [Google Scholar]
- 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]
- Falini B., Flenghi L., Pileri S., Pelicci P., Fagioli M., Martelli M. F., Moretta L., Ciccone E. Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. J Immunol. 1989 Oct 15;143(8):2480–2488. [PubMed] [Google Scholar]
- Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
- Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
- Häcker G., Kromer S., Heeg K., Ivanyi J., Wagner H., Pfeffer K. Opportunist mycobacteria express ligands that stimulate production of human V gamma 9V delta 2 T lymphocytes. Infect Immun. 1992 Jul;60(7):2753–2757. doi: 10.1128/iai.60.7.2753-2757.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kabelitz D., Bender A., Schondelmaier S., Schoel B., Kaufmann S. H. A large fraction of human peripheral blood gamma/delta + T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein. J Exp Med. 1990 Mar 1;171(3):667–679. doi: 10.1084/jem.171.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann S. H., Blum C., Yamamoto S. Crosstalk between alpha/beta T cells and gamma/delta T cells in vivo: activation of alpha/beta T-cell responses after gamma/delta T-cell modulation with the monoclonal antibody GL3. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9620–9624. doi: 10.1073/pnas.90.20.9620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lang F., Peyrat M. A., Constant P., Davodeau F., David-Ameline J., Poquet Y., Vié H., Fournié J. J., Bonneville M. Early activation of human V gamma 9V delta 2 T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands. J Immunol. 1995 Jun 1;154(11):5986–5994. [PubMed] [Google Scholar]
- McMenamin C., Pimm C., McKersey M., Holt P. G. Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells. Science. 1994 Sep 23;265(5180):1869–1871. doi: 10.1126/science.7916481. [DOI] [PubMed] [Google Scholar]
- McVay L. D., Carding S. R., Bottomly K., Hayday A. C. Regulated expression and structure of T cell receptor gamma/delta transcripts in human thymic ontogeny. EMBO J. 1991 Jan;10(1):83–91. doi: 10.1002/j.1460-2075.1991.tb07923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
- Mombaerts P., Arnoldi J., Russ F., Tonegawa S., Kaufmann S. H. Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen. Nature. 1993 Sep 2;365(6441):53–56. doi: 10.1038/365053a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Parker C. M., Groh V., Band H., Porcelli S. A., Morita C., Fabbi M., Glass D., Strominger J. L., Brenner M. B. Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J Exp Med. 1990 May 1;171(5):1597–1612. doi: 10.1084/jem.171.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeffer K., Schoel B., Gulle H., Kaufmann S. H., Wagner H. Primary responses of human T cells to mycobacteria: a frequent set of gamma/delta T cells are stimulated by protease-resistant ligands. Eur J Immunol. 1990 May;20(5):1175–1179. doi: 10.1002/eji.1830200534. [DOI] [PubMed] [Google Scholar]
- 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]
- Raulet D. H. The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol. 1989;7:175–207. doi: 10.1146/annurev.iy.07.040189.001135. [DOI] [PubMed] [Google Scholar]
- Rosat J. P., MacDonald H. R., Louis J. A. A role for gamma delta + T cells during experimental infection of mice with Leishmania major. J Immunol. 1993 Jan 15;150(2):550–555. [PubMed] [Google Scholar]
- Schoel B., Sprenger S., Kaufmann S. H. Phosphate is essential for stimulation of V gamma 9V delta 2 T lymphocytes by mycobacterial low molecular weight ligand. Eur J Immunol. 1994 Aug;24(8):1886–1892. doi: 10.1002/eji.1830240826. [DOI] [PubMed] [Google Scholar]
- Tanaka Y., Sano S., Nieves E., De Libero G., Rosa D., Modlin R. L., Brenner M. B., Bloom B. R., Morita C. T. Nonpeptide ligands for human gamma delta T cells. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8175–8179. doi: 10.1073/pnas.91.17.8175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ueta C., Tsuyuguchi I., Kawasumi H., Takashima T., Toba H., Kishimoto S. Increase of gamma/delta T cells in hospital workers who are in close contact with tuberculosis patients. Infect Immun. 1994 Dec;62(12):5434–5441. doi: 10.1128/iai.62.12.5434-5441.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wallace R. J., Jr, Nash D. R., Tsukamura M., Blacklock Z. M., Silcox V. A. Human disease due to Mycobacterium smegmatis. J Infect Dis. 1988 Jul;158(1):52–59. doi: 10.1093/infdis/158.1.52. [DOI] [PubMed] [Google Scholar]