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. 1993 Feb;61(2):439–447. doi: 10.1128/iai.61.2.439-447.1993

Mycobacterial antigen complex A60-specific T-cell repertoire during the course of pulmonary tuberculosis.

S Carlucci 1, A Beschin 1, L Tuosto 1, F Ameglio 1, G M Gandolfo 1, C Cocito 1, F Fiorucci 1, C Saltini 1, E Piccolella 1
PMCID: PMC302748  PMID: 8423072

Abstract

The Mycobacterium bovis antigen complex A60 is known to be immunodominant in tuberculosis and to have a protective effect against experimental infection in vitro and in vivo. To identify immunodominant and possibly protective antigens in pulmonary tuberculosis, the T-cell repertoire directed to nitrocellulose-bound fractions of A60 antigen was analyzed in active tuberculosis patients during the course of the infection and after recovery. The results show that patients infected with Mycobacterium tuberculosis acquired complete A60-T-cell reactivity only in the late phases of infection. At disease onset, patients with active tuberculosis were characterized by (i) T-cell unresponsiveness to most A60 fractions, (ii) high tumor necrosis factor alpha production, and (iii) low gamma interferon (IFN-gamma) release. Several weeks after chemotherapy, the unresponsive state disappeared and the following reverse situation was observed: (i) high blastogenic response to almost all A60 fractions, (ii) low tumor necrosis factor alpha release, and (iii) high IFN-gamma production. In addition, 60% of these patients significantly responded against seven A60 fractions (61 to 58, 56 to 53, 49 to 46, 46 to 44, 35 to 33, 33 to 30, and 30 to 28 kDa), indicating that they included immunodominant antigens. Furthermore, only the fractions within the molecular mass ranges of 56 to 44 and 35 to 28 kDa induced IFN-gamma synthesis. One year after complete recovery from infection, more than 60% of past-active tuberculosis subjects had memory T cells specific for the immunodominant fractions of 61 to 58, 56 to 53, 49 to 46, and 33 to 30 kDa. Since the same fractions induced the strongest IFN-gamma production, known to exhibit antimycobacterial effects, it is suggested that these may represent the inducers of a protective immune response.

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Selected References

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  1. Abou-Zeid C., Filley E., Steele J., Rook G. A. A simple new method for using antigens separated by polyacrylamide gel electrophoresis to stimulate lymphocytes in vitro after converting bands cut from Western blots into antigen-bearing particles. J Immunol Methods. 1987 Apr 2;98(1):5–10. doi: 10.1016/0022-1759(87)90429-7. [DOI] [PubMed] [Google Scholar]
  2. Abou-Zeid C., Garbe T., Lathigra R., Wiker H. G., Harboe M., Rook G. A., Young D. B. Genetic and immunological analysis of Mycobacterium tuberculosis fibronectin-binding proteins. Infect Immun. 1991 Aug;59(8):2712–2718. doi: 10.1128/iai.59.8.2712-2718.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andersen P., Askgaard D., Ljungqvist L., Bentzon M. W., Heron I. T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis. Infect Immun. 1991 Apr;59(4):1558–1563. doi: 10.1128/iai.59.4.1558-1563.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnes P. F., Fong S. J., Brennan P. J., Twomey P. E., Mazumder A., Modlin R. L. Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis. J Immunol. 1990 Jul 1;145(1):149–154. [PubMed] [Google Scholar]
  5. Barnes P. F., Mehra V., Hirschfield G. R., Fong S. J., Abou-Zeid C., Rook G. A., Hunter S. W., Brennan P. J., Modlin R. L. Characterization of T cell antigens associated with the cell wall protein-peptidoglycan complex of Mycobacterium tuberculosis. J Immunol. 1989 Oct 15;143(8):2656–2662. [PubMed] [Google Scholar]
  6. Beschin A., Brijs L., De Baetselier P., Cocito C. Mycobacterial proliferation in macrophages is prevented by incubation with lymphocytes activated in vitro with a mycobacterial antigen complex. Eur J Immunol. 1991 Mar;21(3):793–797. doi: 10.1002/eji.1830210336. [DOI] [PubMed] [Google Scholar]
  7. Closs O., Harboe M., Axelsen N. H., Bunch-Christensen K., Magnusson M. The antigens of Mycobacterium bovis, strain BCG, studied by crossed immunoelectrophoresis: a reference system. Scand J Immunol. 1980;12(3):249–263. doi: 10.1111/j.1365-3083.1980.tb00065.x. [DOI] [PubMed] [Google Scholar]
  8. Cocito C. G. Properties of the mycobacterial antigen complex A60 and its applications to the diagnosis and prognosis of tuberculosis. Chest. 1991 Dec;100(6):1687–1693. doi: 10.1378/chest.100.6.1687. [DOI] [PubMed] [Google Scholar]
  9. Cocito C., Vanlinden F. Preparation and properties of antigen 60 from Mycobacterium bovis BCG. Clin Exp Immunol. 1986 Nov;66(2):262–272. [PMC free article] [PubMed] [Google Scholar]
  10. Cocito C., Vanlinden F. Subcellular localisation and sedimentation behaviour of antigen 60 from Mycobacterium bovis BCG. Med Microbiol Immunol. 1988;177(1):15–25. doi: 10.1007/BF00190307. [DOI] [PubMed] [Google Scholar]
  11. Collins F. M., Lamb J. R., Young D. B. Biological activity of protein antigens isolated from Mycobacterium tuberculosis culture filtrate. Infect Immun. 1988 May;56(5):1260–1266. doi: 10.1128/iai.56.5.1260-1266.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Douvas G. S., Looker D. L., Vatter A. E., Crowle A. J. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect Immun. 1985 Oct;50(1):1–8. doi: 10.1128/iai.50.1.1-8.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ellner J. J. Suppressor adherent cells in human tuberculosis. J Immunol. 1978 Dec;121(6):2573–2579. [PubMed] [Google Scholar]
  14. Ellner J. J., Wallis R. S. Immunologic aspects of mycobacterial infections. Rev Infect Dis. 1989 Mar-Apr;11 (Suppl 2):S455–S459. doi: 10.1093/clinids/11.supplement_2.s455. [DOI] [PubMed] [Google Scholar]
  15. Fabre I., L'Homme O., Bruneteau M., Michel G., Cocito C. Chemical composition of antigen 60 from Mycobacterium bovis BCG. Scand J Immunol. 1986 Nov;24(5):591–602. doi: 10.1111/j.1365-3083.1986.tb02175.x. [DOI] [PubMed] [Google Scholar]
  16. Gilardini Montani M. S., Del Gallo F., Lombardi G., Del Porto P., Piccolella E., Arienzo F., Colizzi V. Limiting dilution analysis of T cell unresponsiveness to mycobacteria in advanced disseminated tuberculosis. Med Microbiol Immunol. 1989;178(5):235–244. doi: 10.1007/BF00191058. [DOI] [PubMed] [Google Scholar]
  17. Grange J. M. The humoral immune response in tuberculosis: its nature, biological role and diagnostic usefulness. Adv Tuberc Res. 1984;21:1–78. [PubMed] [Google Scholar]
  18. Havlir D. V., Wallis R. S., Boom W. H., Daniel T. M., Chervenak K., Ellner J. J. Human immune response to Mycobacterium tuberculosis antigens. Infect Immun. 1991 Feb;59(2):665–670. doi: 10.1128/iai.59.2.665-670.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kaufmann S. H., Flesch I. E. The role of T cell--macrophage interactions in tuberculosis. Springer Semin Immunopathol. 1988;10(4):337–358. doi: 10.1007/BF02053845. [DOI] [PubMed] [Google Scholar]
  20. Kingston A. E., Salgame P. R., Mitchison N. A., Colston M. J. Immunological activity of a 14-kilodalton recombinant protein of Mycobacterium tuberculosis H37Rv. Infect Immun. 1987 Dec;55(12):3149–3154. doi: 10.1128/iai.55.12.3149-3154.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kleinhenz M. E., Ellner J. J., Spagnuolo P. J., Daniel T. M. Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility. J Clin Invest. 1981 Jul;68(1):153–162. doi: 10.1172/JCI110231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Lombardi G., Di Massimo A. M., Del Gallo F., Vismara D., Piccolella E., Pugliese O., Colizzi V. Mechanism of action of an antigen nonspecific inhibitory factor produced by human T cells stimulated by MPPS and PPD. Cell Immunol. 1986 Apr 1;98(2):434–443. doi: 10.1016/0008-8749(86)90302-3. [DOI] [PubMed] [Google Scholar]
  24. Manca F., Rossi G., Valle M. T., Lantero S., Li Pira G., Fenoglio D., De Bruin J., Costantini M., Damiani G., Balbi B. Limited clonal heterogeneity of antigen-specific T cells localizing in the pleural space during mycobacterial infection. Infect Immun. 1991 Feb;59(2):503–513. doi: 10.1128/iai.59.2.503-513.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Munk M. E., Schoel B., Kaufmann S. H. T cell responses of normal individuals towards recombinant protein antigens of Mycobacterium tuberculosis. Eur J Immunol. 1988 Nov;18(11):1835–1838. doi: 10.1002/eji.1830181128. [DOI] [PubMed] [Google Scholar]
  26. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oftung F., Mustafa A. S., Husson R., Young R. A., Godal T. Human T cell clones recognize two abundant Mycobacterium tuberculosis protein antigens expressed in Escherichia coli. J Immunol. 1987 Feb 1;138(3):927–931. [PubMed] [Google Scholar]
  28. Orme I. M. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J Immunol. 1988 May 15;140(10):3589–3593. [PubMed] [Google Scholar]
  29. Orme I. M. Induction of nonspecific acquired resistance and delayed-type hypersensitivity, but not specific acquired resistance in mice inoculated with killed mycobacterial vaccines. Infect Immun. 1988 Dec;56(12):3310–3312. doi: 10.1128/iai.56.12.3310-3312.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Piccolella E., Dolei A., Lombardi G., Vismara D., Pizzoli P., Colizzi V., Dianzani F. Regulation of immune interferon production during the response to soluble microbial antigens. Clin Exp Immunol. 1986 Jul;65(1):190–197. [PMC free article] [PubMed] [Google Scholar]
  31. Sussman G., Wadee A. A. Production of a suppressor factor by CD8+ lymphocytes activated by mycobacterial components. Infect Immun. 1991 Aug;59(8):2828–2835. doi: 10.1128/iai.59.8.2828-2835.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Takashima T., Ueta C., Tsuyuguchi I., Kishimoto S. Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis. Infect Immun. 1990 Oct;58(10):3286–3292. doi: 10.1128/iai.58.10.3286-3292.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vismara D., Mezzopreti M. F., Gilardini Montani M. S., Gilardini M. S., Del Porto P., Lombardi G., Piccolella E., Damiani G., Rappuoli R., Colizzi V. Identification of a 35-kilodalton Mycobacterium tuberculosis protein containing B- and T-cell epitopes. Infect Immun. 1990 Jan;58(1):245–251. doi: 10.1128/iai.58.1.245-251.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wadee A. A., Sher R., Rabson A. R. Production of a suppressor factor by human adherent cells treated with mycobacteria. J Immunol. 1980 Sep;125(3):1380–1386. [PubMed] [Google Scholar]
  35. Wallis R. S., Amir-Tahmasseb M., Ellner J. J. Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot. Proc Natl Acad Sci U S A. 1990 May;87(9):3348–3352. doi: 10.1073/pnas.87.9.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Young D. B., Garbe T. R. Heat shock proteins and antigens of Mycobacterium tuberculosis. Infect Immun. 1991 Sep;59(9):3086–3093. doi: 10.1128/iai.59.9.3086-3093.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van Oers M. H., Pinkster J., Zeijlemaker W. P. Quantification of antigen-reactive cells among human T lymphocytes. Eur J Immunol. 1978 Jul;8(7):477–484. doi: 10.1002/eji.1830080706. [DOI] [PubMed] [Google Scholar]

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