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Suppressor Cells in Mycobacterial Infections

  • Reiko M. Nakamura
  • Tohru Tokunaga
Part of the Infectious Agents and Pathogenesis book series (IAPA)

Abstract

Mycobacterium bovis BCG has been widely used as the antituberculosis vaccine and is also a well-known immunopotentiator in both humoral and cell-mediated immune responses. Bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis is an indispensable component of Freund’s complete adjuvant and has been used in various experimental systems to potentiate immune responses. Because of its adjuvant activity, BCG has been used for immunotherapy of cancer, such as acute lymphoid leukemias1 or melanomas2 in humans. There are quite a few reports in this field both in animal experiments and in human cases,3–7 many of which indicated improvement or even cure of the tumor by the immunotherapy with BCG. However, several reports show enhanced tumor growth by treatment with BCG. Likhite4 reported that in some instances tumor growth was enhanced by BCG injection in rats. Piessens et al.8 showed that injection of a tumor cell-BCG mixture into rats resulted in either suppressed or enhanced growth of the tumor depending on the dose of BCG. Mathe,9 who had emphasized the immunotherapeutic effect of BCG, even found that a high dose of BCG suppresses antibody production against sheep red blood cells (SRBC) in mice. BCG injected intravenously (IV) induced suppressed immunity to rodent malaria.10 Thus, it has been known for some time that the famous immunopotentiator BCG has double-faced activity, modulating immune responses either into a positive (immunity) or negative (suppression) direction.

Keywords

Suppressor Cell Mycobacterial Infection Purify Protein Derivative Mycobacterium Bovis Suppressor Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Mathé, G., 1976, Surviving in company of BCG, Cancer Immunol. Immunother. 1:3–5.Google Scholar
  2. 2.
    Morton, D. L., Eilber, F. R., Holmes, E. C., Sparks, F. C., and Ramming, K., 1976, BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma. Med. Clin. North Am. 60:431–439.PubMedGoogle Scholar
  3. 3.
    Hawrylko, E., 1977, Influence of BCG-potentiated immunotherapy in tumor-bearing mice, J. Natl. Cancer Inst. 59:359–365.Google Scholar
  4. 4.
    Likhite, V. V., 1976, Experimental cancer Immunotherapy: Comparison of tumor rejection in F344 rats given live Mycobacterium bovis (strain BCG) and killed Corynbac-terium parvum, J. Natl. Cancer Inst. 56:985–989.PubMedGoogle Scholar
  5. 5.
    Bast, R. C., Zbar, B., Borsos, T. ,and Rapp, H. J. ,1974, BCG and cancer, N. Engl. J. Med. 290:1413–1420.PubMedCrossRefGoogle Scholar
  6. 6.
    Mathé, G., Shwarzenberg, L., DeVassal, G., Delgado, M., Pena-Angulo, J., Belponne, E., Poullart, P., Machover, D., Misset, J. L., Pico, J. L., Jasmin, C., Hayat, M., Schneider, M., Cattan, A., Amiel, J. L., Musset, M., and Rosenfeld, C., Chemotherapy followed by active immunotherapy in the treatment of acute lymphoid leukemias for patients of all ages, in: Immunotherapy of cancer: Present status of trials in man (W. D. Terry and D. W. Windhorst, eds.), pp. 451–469, Raven, New York.Google Scholar
  7. 7.
    Yamamura, Y., Kitagawa, M., and Azuma, I. (eds.), Cancer Immunology and Its Immunological Basis ,Japan Science Society Press-Tokyo, University Park Press, Baltimore, 1978.Google Scholar
  8. 8.
    Piessens, W. F., Campbell, M., and Churchill, W. H., 1977, Inhibition or enhancement of rat mammary tumors dependent on dose of BCG, J. Natl. Cancer Inst. 59:207–211.PubMedGoogle Scholar
  9. 9.
    Mathé, G., 1976, Active Immunotherapy of Cancer. Its Immunoprophylaxis and Immu-norestoration ,Springer, New York.Google Scholar
  10. 10.
    Smrkovski, L. L., 1981, Effect of route of Mycobacterium bovis BCG administration on induction of suppression of sporozoite immunity in rodent malaria, Infect. Immun. 31:408–412.PubMedGoogle Scholar
  11. 11.
    Geffard, M., and Orbach-Arbouys, S., 1976, Enhancement of T suppressor activity in mice by high doses of BCG, Cancer Immunol. Immunother. 1: 41–43.CrossRefGoogle Scholar
  12. 12.
    Collins, F. M., and Watson, S. R., 1979, Suppressor T-cells in BCG-infected mice, Infect. Immun. 25:491–496.PubMedGoogle Scholar
  13. 13.
    Nakamura, R. M., and Tokunaga, T., 1980, Induction of suppressor T cells in delayed-type hypersensitivity to Mycobacterium bovis BCG in low-responder mice, Infect. Immun. 28:331–335.PubMedGoogle Scholar
  14. 14.
    Kendall, L., and Sabbadini, E., 1981, Effect of Bacillus Calmétte-Guerin on the in vitro generation of cytotoxic T lymphocytes. I. Effect of BCG on the frequency of cytotoxic T lymphocyte precursors and on the production of helper factors, J. Immunol. 127:234–238.PubMedGoogle Scholar
  15. 15.
    Moore, V. L., Mondloch, V. M., Pederson, G. M., Schrier, D. J., and Allen, E. M., 1981, Strain variation in BCG-induced chronic pulmonary inflammation in mice: Control by a cyclophosphamide-sensitive thymus-derived suppressor cell, J. Immunol. 127:339– 342.PubMedGoogle Scholar
  16. 16.
    Turcotte, R., 1981, Evidence for two distinct populations of suppressor cells in the spleens of Mycobacterium bovis BCG-sensitized mice, Infect. Immun. 34:315–322.PubMedGoogle Scholar
  17. 17.
    Florentin, I., Huchent, R., Bruley-Rosset, M., Halle-Pennenko, O., and Mathé, G., 1976, Studies on the mechanisms of action of BCG, Cancer Immunol. Immunother. 1:31– 39.Google Scholar
  18. 18.
    Klimple, G. R., and Henney, C. S., 1978, BCG-induced suppressor cells. I. Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro, J. Immunol. 120:563–569.Google Scholar
  19. 19.
    Ellner, J. J., 1978, Suppressor adherent cells in human tuberculosis, J. Immunol. 121:2573–2579.PubMedGoogle Scholar
  20. 20.
    Allen, E. M., and Moore, V. L., 1979, Suppression of phytohemagglutinin and lipopolysaccharide responses in mouse spleen cells by Bacillus Calmette-Guérin, J. Re-ticuloendothel. Soc. 26:349–336.Google Scholar
  21. 21.
    Novogrodsky, A., Rubin, A. L., and Stenzel, K. H., 1979, Selective suppression by adherent cells, prostaglandin, and cyclic AMP analogues of blastogenesis induced by different mitogens, J. Immunol. 122:1–7.PubMedGoogle Scholar
  22. 22.
    Colizzi, V., 1984, In vivo and in vitro administration of interleukin 2-containing preparation reverses T-cell unresponsiveness in Mycobacterium bovis BCG-infected mice. Infect. Immun. 45:25–28.PubMedGoogle Scholar
  23. 23.
    DeSilva, M. A., Wepsic, H. T., Mizushima, Y., Nikcevich, D. A., and Larson, C. H., 1985, Modification of in vitro BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin, J. Natl. Cancer Inst. 74:917–921.PubMedGoogle Scholar
  24. 24.
    Shepard, C. C., Walker, L. L., Van Landingham, R. M., and Ye, S. Z., 1982, Sensitization or tolerance to Mycobacterium leprae antigen by route of injection, Infect. Immun. 38:637–680.Google Scholar
  25. 25.
    Nakamura, R. M., and Tokunaga, T., 1978, Strain difference of delayed-type hypersensitivity to BCG and its genetic control in mice, Infect. Immun. 22:657–664.PubMedGoogle Scholar
  26. 26.
    Watson, S., and Collins, F. M., 1980, The specificity of suppressor T cells induced by chronic Mycobacterium avium infection in mice, Clin. Exp. Immunol. 43:10–19.Google Scholar
  27. 27.
    Turcotte, R., and Lemieux, S., 1982, Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis, Infect. Immun. 36:263–270.PubMedGoogle Scholar
  28. 28.
    Janss, G., Wepsic, H. T., Mizushima, Y., DeSilva, M. A., and Larson, C. H., 1984, The inhibition of fatal graft-versus-host disease by immunization of donor or host with BCG cell walls, Transplantation 38:407–411.PubMedCrossRefGoogle Scholar
  29. 29.
    Kato, K., Yamamoto, K., Kimura, T., Azuma, I., and Askenase, P. W., 1984, Suppression of BCG cell wall-induced delayed-type hypersensitivity by pretreatment with killed BCG: Induction of nonspecific suppressor T cells by the adjuvant portion (MDP) and of specific suppressor T cells by the antigen portion (TAP), J. Immunol. 132:2790– 2795.PubMedGoogle Scholar
  30. 30.
    Turk, J. L., and Bryceson, A. D. M., 1971, Immunological phenomona in leprosy and related diseases, Adv. Immunol. 13:209–266.PubMedCrossRefGoogle Scholar
  31. 31.
    Bloom, B. R., and Mehra, V., 1984, Immunological unresponsiveness in leprosy, Immunol. Rev. 80:5–28.PubMedCrossRefGoogle Scholar
  32. 32.
    Bullock, W. E., 1968, Studies of immune mechanisms in leprosy. 1. Depression of delayed allergic response to skin test antigens, N. Engl. J. Med. 278:298–304.CrossRefGoogle Scholar
  33. 33.
    Myrvang, B., Godal, T., Ridley, D. S., Fröland, S. S., and Song, Y. K., 1973, Immune responsiveness to Mycobacterium leprae and other mycobacterial antigens throughout the clinical and histopathological spectrum of leprosy, Clin. Exp. Immunol. 14:541–553.PubMedGoogle Scholar
  34. 34.
    Mehra, V. L., Talwar, G. P., Balakrishnan, K., and Bhutani, L. K., 1972, Influence of chemotherapy and serum factors on the mitogenic response of peripheral leucocytes of leprosy patients to phytohaemagglutinin, Clin. Exp. Immunol. 12:205–213.PubMedGoogle Scholar
  35. 35.
    Mehra, V., Mason, L. H., Fields, J. P., and Bloom, B. R., 1979, Lepromin-induced suppressor cells in patients with leprosy, J. Immunol. 123:1813–1817.PubMedGoogle Scholar
  36. 36.
    Mehra, V., Convit, J., Rubinstein, A., and Bloom, B. R., 1982, Activated suppressor T cells in leprosy, J. Immunol. 129:1946–1951.PubMedGoogle Scholar
  37. 37.
    Convit, J., Aranzazu, N., Pinardi, M., and Ulrich, M., 1979, Immunological changes observed in indeterminate and lepromatous leprosy patients and Mitsuda-negative contacts after the inoculation of a mixture of Mycobacterium leprae and BCG, Clin. Exp. Immunol. 36:214–220.PubMedGoogle Scholar
  38. 38.
    Stoner, G. L., Mshana, R. N., Touw, J. ,and Belehu, A., 1982, Studies on the defect in cell-mediated immunity in lepromatous leprosy using HLA-D-identical siblings. Absence of circulating suppressor cells and evidence that the defect is the T-lymphocyte, rather than the monocyte, population, Scand. J. Immunol. 15:33–48.PubMedCrossRefGoogle Scholar
  39. 39.
    Watson, S. R., and Collins, F. M., 1979, Development of suppressor T-cells in Mycobacterium habana-mfected mice, Infect. Immun. 25:497–506.PubMedGoogle Scholar
  40. 40.
    Bullock, W. E. ,Carlson, E. M., and Gershon, R. K. ,1978, The evolution of immunosuppressive cell populations in experimental mycobacterial infection, J. Immunol. 120:1709–1716.PubMedGoogle Scholar
  41. 41.
    Hoffenbach, A. ,Lagrange, P. H. ,and Bach, M. A., 1983, Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection, Infect. Immun. 39:109–116.PubMedGoogle Scholar
  42. 42.
    Lefford, M. J., Patel, P. J., Poulter, L. W., and Mackaness, G. B., 1977, Induction of cell-mediated immunity to Mycobacterium lepraemurium in susceptible mice, Infect. Immun. 18:654–659.PubMedGoogle Scholar
  43. 43.
    Lagrange, P. M. ,and Hurtrel, B., 1979, Local immune response to Mycobacterium lepraemurium in C3H and C57BL/6 mice, Clin. Exp. Immunol. 38:461–474.PubMedGoogle Scholar
  44. 44.
    Ha, D. K. K., Gardner, I. D., and Lawton, J. W., 1983, Macrophage function in Mycobacterium lepraemurium infection: morphological and functional changes of peritoneal and splenic macrophages in vitro, Infect. Immun. 39:353–361.PubMedGoogle Scholar
  45. 45.
    Løvik, M., Collins, F. M. ,and Closs, O., 1982, Inbred C3H mouse substrains differences demonstrated in experimental murine leprosy, Immunogenetics 16:607–611.PubMedCrossRefGoogle Scholar
  46. 46.
    Curtis, J., Adu, H. O. ,and Turk, J. L., 1982, H-2 linkage control of resistance to subcutaneous infection with Mycobacterium lepraemurium, Infect. Immun. 38:434–439.PubMedGoogle Scholar
  47. 47.
    Skamene, E., Gros, P., Forget, A. ,Patel, P. J., and Nesbitt, M. N., 1984, Regulation of resistance to leprosy by chromosome 1 locus in the mouse, Immunogenetics 19: 117–124.PubMedCrossRefGoogle Scholar
  48. 48.
    Nakamura, R. M., Tanaka, H., and Tokunaga, T., 1982, In vitro induction of suppressor T-cells in delayed-type hypersensitivity to BCG and an essential role of I-J positive accessory cells, Immunol. Lett. 4:295–299.PubMedCrossRefGoogle Scholar
  49. 49.
    Nakamura, R. M., and Tokunaga, T., 1984, I-J positive macrophages in induction of suppressor T cells against delayed-type hypersensitivity to Mycobacterium bovis BCG, in: Microbiology 1984 ,pp. 363–365, American Society of Microbiology, Washington, D. C.Google Scholar
  50. 50.
    Nakamura, R. M., Nakamura, Y. ,Nagayama, A., and Tokunaga, T., 1986, I-J positive cloned macrophages as the accessory cells for the induction of suppressor T cells in vitro, Immunol. Res. 5:106–116.PubMedCrossRefGoogle Scholar
  51. 51.
    Lowy, A., Tominaga, A. ,Drebin, J. A., Takaoki, M., Benacerraf, B., and Greene, M. I., 1983, Identification of an I-J + antigen-presenting cell required for third order suppressor cell activation, J. Exp. Med. 157:353–358.PubMedCrossRefGoogle Scholar
  52. 52.
    Noma, T., Usui, M., and Dorf, M. E., 1985, Characterization of the accessory cells involved in suppressor T cell induction, J. Immunol. 134: 1374–1380.PubMedGoogle Scholar
  53. 53.
    Nakamura, Y., Nakamura, R. M., and Tokunaga, T., 1986, The cell-cell interaction responsible for the induction of the first order suppressor T cells in hapten-specific contact sensitivity reaction, Immunol. Res. 5: 117–128.PubMedCrossRefGoogle Scholar
  54. 54.
    Steinmetz, M., Minard, K., Horvath, S., McNicholas, J., Sretinger, J. ,Wake, C., Long, E., Mach, B., and Hood, L., 1983. A molecular map of the immune response region from the major histocompatibility complex of the mouse, Nature (Lond.) 300: 35–42.CrossRefGoogle Scholar
  55. 55.
    Kronenberg, M., Steinmetz, M., Kobori, J., Kraig, E., Kapp, J., Pierce, C. W., Sorensen, C. M., Suzuki, G., Tada, T., and Hood, L., 1983, RNA transcripts for I-J polypeptides are apparently not encoded between the I-A and I-E subregions of the murine major histocompatibility complex, Proc. Natl. Acad. Sci. USA 80:5704–5708.PubMedCrossRefGoogle Scholar
  56. 56.
    Granstein, R. D., Lowy, A., and Greene, M. I., 1984, Epidermal antigen-presenting cells in activation of suppression: identification of a new functional type of ultraviolet radiation-resistant epidermal cells, J. Immunol. 132:563–565.PubMedGoogle Scholar
  57. 57.
    Granstein, R. D., Tominaga, A., Mizel, S. B., and Greene, M. I., 1985, Defective antigen-presenting cell function and interleukins, in: Limphokines ,Vol. 12 (E. Pick, ed.), pp. 57–74, Academic, New York.Google Scholar
  58. 58.
    Colizzi, V., Ferluga, J., Garreau, F., Malkovsky, M., and Asherson, G. L., 1984, Suppressor cells induced by BCG release nonspecific factors in vitro which inhibit DNA synthesis and interleukin-2 production, Immunology 51:65–71.PubMedGoogle Scholar
  59. 59.
    Haregewoin, A., Godal, T., Mustafa, A. S., Belehu, A., and Yamaneberhan, T., 1983, T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy, Nature (Lond.) 303: 342–344.CrossRefGoogle Scholar
  60. 60.
    Haregewoin, A., Mustaga, A. S., Helle, I., Waters, M. F. R., Leiker, D. L., and Godal, T., 1984, Reversal by interleukin-2 of the T cell unresponsiveness of lepromatous leprosy to Mycobacterium leprae, Immunol. Rev. 80:77–86.PubMedCrossRefGoogle Scholar
  61. 61.
    Mohagheghpour, N., Gelber, R. H., Larrick, J. W., Sasaki, D. T., Brennan, P. J., and Engleman, E. G., 1985, Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2, J. Immunol. 135:1443–1449.PubMedGoogle Scholar
  62. 62.
    Modulin, R. L., Hofman, F. M., Horwitz, D. A., Hasmann, L. A., Gillis, S., Taylor, C. R., and Rea, T. H., 1984, In situ identification of cells in human leprosy granulomas with monoclonal antibodies to interleukin 2 and its receptor, J. Immunol. 132:3085– 3090.Google Scholar
  63. 63.
    Nogueira, N., Kaplan, G., Levy, E., Sarno, E. N., Kushner, P., Granelli-Piperno, A., Vierra, L., Gould, V. C., Levis, W., Steinman, R., Yip, Y. K., and Cohn, Z. A., 1983, Defective 7-interferon production in leprosy. Reversal with antigen and interleukin 2, J. Exp. Med. 158:2165–2170.PubMedCrossRefGoogle Scholar
  64. 64.
    Sathish, M., Bhutani, L. K., Sharma, A. K. ,and Nath, I., 1983, Monocyte-derived soluble suppressor factor(s) in patients with lepromatous leprosy, Infect. Immun. 42:890–899.PubMedGoogle Scholar
  65. 65.
    Honda, M., Chan, C., and Shevach, E., 1985, Characterization and partial purification of a specific interleukin 2 inhibitor, J. Immunol. 135: 1834–1839.PubMedGoogle Scholar
  66. 66.
    Hardt, C., Röllinghoff, M., Pfizenmaier, K., Mosmann, H., and Wagner, H., 1981, Lyt-23 + cyclophosphamide-sensitive T cells regulate the activity of interleukin 2 inhibitor in vitro, J. Exp. Med. 154:262–274.PubMedCrossRefGoogle Scholar
  67. 67.
    Fontana, A., Hengartner, H., Tribolet, N., and Weber, E., 1984, Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects, J. Immunol. 132:1837–1844.PubMedGoogle Scholar
  68. 68.
    Kirchheimer, W. F., and Storrs, E. E., 1971, Attempts to establish the armadillo (Dasypus nevemcinctus Lnn.) as a model for the study of leprosy, Int. J. Lepr. 39:693–702.Google Scholar
  69. 69.
    Gillis, T. P., and Buchanan, T. M., 1982, Production and partial characterization of monoclonal antibodies to Mycobacterium leprae, Infect. Immun. 37: 172–178.PubMedGoogle Scholar
  70. 70.
    Ivanyi, J., Sinha, S., Aston, R., Cussell, D., Keen, M., and Sengupta, U., 1983, Definition of species specific and cross-reactive antigenic determinants of Mycobacterium leprae using monoclonal antibodies, Clin. Exp. Immunol. 52:528–536.PubMedGoogle Scholar
  71. 71.
    Hunter, S. W., Fujiwara, T., and Brennan, P. J., 1982, Structure and antigenicity of the major specific glycolipid antigen of Mycobacterium leprae, J. Biol. Chem. 257: 15072– 15078.PubMedGoogle Scholar
  72. 72.
    Mehra, V., Brennan, P. J., Rada, E., Convit, J., and Bloom, B. R., 1984, Lymphocyte suppression in leprosy induced by unique M. leprae glycolipid, Nature (Lond.) 308: 194– 196.CrossRefGoogle Scholar
  73. 73.
    Cho, S-N., Hunter, S. W., Gelber, R. H., Rea, T. H., and Brenna, P. J., 1986, Quantitation of the phenolic glycolipid of Mycobacterium leprae and relevance to glycolipid anti-genemia in leprosy, J. Infect. Dis. 153:560–569.PubMedCrossRefGoogle Scholar
  74. 74.
    Young, R. A., Bloom, B. R., Grosskinsky, C. M., Ivanyi, J., Thomas, D., and Davis, R. W., 1985, Dissection of Mycobacterium tuberculosis antigens using recombinant DNA, Proc. Natl. Acad. Sci. USA 82:2583–2587.PubMedCrossRefGoogle Scholar
  75. 75.
    Minden, P., Kelleher, P. J., Freed, J. H., Nielsen, L. D., Brenna, P. J., McPheron, L., and McClatchy, J. K., 1984, Immunological evaluation of a component isolated from Mycobacterium bovis BCG with a monoclonal antibody to M. bovis BCG, Infect. Immun. 46:519–525.PubMedGoogle Scholar
  76. 76.
    Wadee, A. A. ,Mendelsohn, D., and Rabson, A. R., 1983, Characterization of a suppressor cell-activating factor (SCAF) released by adherent cells treated with M. tuberculosis, J. Immunol. 130:2266–2270.PubMedGoogle Scholar
  77. 77.
    Colizzi, V., Giuntini, M. ,Garzelli, C. ,Campa, M., and Falcone, G. ,1983, Auto-anti-idiotypic antibodies inhibit T-cell-mediated hypersensitivity in BCG-infected mice, Cell. Immunol ,80:205–210.PubMedCrossRefGoogle Scholar
  78. 78.
    Monroe, J. G., Gurish, M. ,Dambrauskas, J. ,Slaoui, M. ,Lowy, A., and Greene, M. I., 1985, Genetic and biological characterization of a T suppressor cell induced by antiidiotypc antibody, J. Immunol. 135: 1589–1597.PubMedGoogle Scholar
  79. 79.
    Dietz, M. H., Sy, M-S., Benacerraf, B., Nisonoff, A., Greene, M. I. ,and Germain, R. N., 1981, Antigen-and receptor-driven regulatory mechanisms. VII. H-2-restricted antiidiotypc suppressor factor from efferent suppressor T cells, J. Exp. Med. 153:450–463.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Reiko M. Nakamura
    • 1
  • Tohru Tokunaga
    • 1
  1. 1.Department of Cellular ImmunologyNational Institutes of HealthKamiosaki, Shinagawa-ku, Tokyo 141Japan

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