Mycobacterium-Induced Suppressor Cells and Their Clinical Importance

  • S. Orbach-Arbouys
Part of the Infectious Agents and Pathogenesis book series (IAPA)


The importance of suppressor cells in mycobacterium-bearing hosts arises from the fact that immunization against tuberculosis and leprosy using BCG vaccines protects in certain areas and fails to give protection in others.1,2 It has thus been suggested that the mycobacterium injection, rather than inducing a protective response, enhances the formation of suppressor cells3,4 which prevent the effector cells from either being formed or from expressing their activity.


Spleen Cell Suppressor Cell Mixed Lymphocyte Reaction Mycobacterium Bovis Leprosy Patient 


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  1. 1.
    Brown, J. A. K., Stone, M. M., and Sutherland, I., 1968, BCG vaccination of children against leprosy in Uganda: Results at the end of second follow up, Br. Med. J. 1:24–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Bechelli, L. M. ,Garbajosa, P. G., Gyi, M. M., Uemura, K., Sundaresan, T., Dominguez, V. M., Matejka, M., Tamondong, C., Quagliato, R., Engler, V., and Altmann, M., 1973, BCG vaccination of children against leprosy: Seven-year findings of the controlled WHO trial in Burma, Bull. WHO 48:323–334.PubMedGoogle Scholar
  3. 3.
    Mehra, V., Convit, J., Rubinstein, A., and Bloom, B. R., 1982, Activated suppressor T cells in leprosy, J. Immunol. 129:1946–1951.PubMedGoogle Scholar
  4. 4.
    Piessens, W. F., Partono, F., Hoffman, S. L., Ratiwayanto, S., Piessens, P. W., Palmieri, J. R., Koiman, I., Dennis, D. T., and Carney, W. P., 1982, Antigen specific suppressor T lymphocytes in human lymphatic filariasis, N. Engl. J. Med. 307:144–147.PubMedCrossRefGoogle Scholar
  5. 5.
    Brown, C. A., Brown, I. N., and Sljivic, V. S., 1980, Active suppression masks an underlying enhancement of antibody production in vitro by spleen cells from BCG-infected mice, Immunology 40:303–309.PubMedGoogle Scholar
  6. 6.
    Orbach-Arbouys, S., and Poupon, M. F., 1978, Active suppression of in vitro reactivity of spleen cells after BCG treatment, Immunology 34:431–437.PubMedGoogle Scholar
  7. 7.
    Orbach-Arbouys, S. ,and Castes, M., 1980, Suppression of T-cell responses to histocompatibility antigens by BCG pretreatment, Immunology 39:263–268.PubMedGoogle Scholar
  8. 8.
    Wing, E. J., 1981, Bacillus Calmette-Guérin (BCG) decreases resistance to Listeria monocytogenes infection in mice, Immunology 44:509–515.PubMedGoogle Scholar
  9. 9.
    Nakamura, R. M., Tanaka, H., and Tokumaga, T., 1982, Strain difference in delayed-type hypersensitivity to BCG in mice: Role of splenic adherent cells in the primary immune response, Immunology 47:729–731.PubMedGoogle Scholar
  10. 10.
    Florentin, I., Huchet, R., Bruley-Rosset, M., Halle-Panenko, O., and Mathé, G., 1976, Studies on the mechanisms of action of BCG, Cancer Immunol. Immunother. 1:31–37.Google Scholar
  11. 11.
    Watson, S. R., and Collins, F. M., 1980, Development of suppressor T cells in mice heavily infected with mycobacteria, Immunology 39:367–375.PubMedGoogle Scholar
  12. 12.
    Collins, F. M., and Cunningham, D. S., 1981, Systemic Mycobacterium kansasii infection and regulation of the alloantigenic response, Infect. Immun. 32:614–624.PubMedGoogle Scholar
  13. 13.
    Collins, F. M. ,and Watson, S. R., 1980, Effect of chemotherapy on suppressor T cells in BCG-infected mice, Immunology 40:529–537.PubMedGoogle Scholar
  14. 14.
    Bullock, W. E., 1978, Leprosy: A model of immunological perturbation in chronic infection, J. Infect. Dis. 137:141–147.CrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Kato, K. ,and Yamamoto, K., 1982, Suppression of BCG cell wall-induced delayed-type hypersensitivity by BCG pretreatment. II. Induction of suppressor T cells by heat-killed BCG injection, Immunology 45:655–661.PubMedGoogle Scholar
  17. 17.
    Mizushima, Y., Wepsic, H. T., Yamamura, Y., DeSilva, M. A. ,Janns, G., and Larson, C. H., 1984, Negative and positive immunobiological responses in mice pretreated with Bacillus Calmette-Guerin cell wall, Cancer Res. 44:20–24.PubMedGoogle Scholar
  18. 18.
    Allen, E. M., Sternick, J. L., Schrier, D. J., and Moore, V. L., 1981, BCG-induced chronic pulmonary inflammation and splenomegaly in mice: Suppression of PHA-induced proliferation, delayed hypersensitivity to sheep erythrocytes, and chronic pulmonary inflammation by soluble factors from adherent spleen cells. Cell. Immunol. 58:61–71.PubMedCrossRefGoogle Scholar
  19. 19.
    Klimpel, G. R., 1979. Soluble factors from BCG-induced suppressor cells inhibit in vitro PFC responses but not cytotoxic responses, Cell. Immunol. 47:218–226.PubMedCrossRefGoogle Scholar
  20. 20.
    Mellow, L., and Sabbadini, E., 1985, Effect of Bacillus Calmette-Guerin on the in vitro generation of cytotoxic T lymphocytes. II. Role of interleukin-I-like factors and soluble suppressor factors, Immunology 56:235–243.PubMedGoogle Scholar
  21. 21.
    Kato, K., Yamamoto, K.-L, Kakinuma, M., Ishihara, C., and Azuma, I. ,1981, Suppression of BCG cell wall induced delayed-type hypersensitivity by BCG pre-treatment. I. Induction of adherent suppressor cells by live BCG injection and their characterization, Immunology 42:259–266.PubMedGoogle Scholar
  22. 22.
    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. 28:331–339.PubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    Hoffenbach, A., Lagrange, P. H., and Bach, M. A., 1983, Surface Lyt phenotype of suppressor cells in C57 Bl/6 mice infected with Mycobacterium lepraemurium, Clin. Exp. Immunol. 51:151 -157.Google Scholar
  25. 25.
    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
  26. 26.
    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
  27. 27.
    Collins, F. M., and Watson, S. R., 1980, Effect of chemotherapy on suppressor T cells in BCG-infected mice, Immunology 40:529–537.PubMedGoogle Scholar
  28. 28.
    Watson, R. S., Auclair, L. K., and Collins, F. M. ,1981, The effect of combined chemotherapy of suppressor T-cell activity in Mycobacterium simian-infected mice, Immunology 43:459–465.PubMedGoogle Scholar
  29. 29.
    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
  30. 30.
    Orbach-Arbouys, S., and Castes, M., 1979, Augmentation of immune responses after methotrexate administration. Immunology 39:265–269.Google Scholar
  31. 31.
    Kato, K., and Yamamoto, K. ,1982, Restoration of suppressed delayed-type hypersensitivity induced in mice by live BCG after methotrexate administration, Int. J. Immu-nopharmacol. 4:463–467.Google Scholar
  32. 32.
    Kato, K., Yamamoto, K., and Kimura, T., 1985, Migration of natural suppressor cells from bone marrow to peritoneal cavity by live BCG, J. Immunol. 135:3661–3668.PubMedGoogle Scholar
  33. 33.
    Collizzi, V., Ferluga, J., Gareau, F., Malkovsky, M., and Asherson, G. L., 1984, Suppressor cells induced by BCG release non-specific factors in vitro which inhibit DNA synthesis and interleukin-2 production, Immunology 51:65–71.Google Scholar
  34. 34.
    Narayanan, R. B., Curtis, J., and Turk, J. L., 1981, Release of soluble factors from lymphe nodes containing mycobacterial granulomas and their effect on fibroblast function in vitro, Cell. Immunol. 63:93–102.CrossRefGoogle Scholar
  35. 35.
    Orme, I. M., Ratcliffe, M. J. H., and Collins, F. M., 1984, Acquired immunity to heavy infection with Mycobacterium bovis bacillus Calmette-Guérin and its relationship to the development of nonspecific unresponsiveness in vitro, Cell. Immunol. 88:285–296.PubMedCrossRefGoogle Scholar
  36. 36.
    Wagner, H., Hardt, C., Heeg, K., Pfizenmaier, K., Solbach, W., Bartlett, R., Stock-inger, H., and Röllinghoff, M., 1980, T-T cell interactions during cytotoxic T lymphocyte (CTL) responses: T cell derived helper factor (interleukin 2) as a probe to analyze CTL responsiveness and thymic maturation of CTL progenitors, Immunol. Rev. 51:215–255.PubMedCrossRefGoogle Scholar
  37. 37.
    Mizel, S. B., 1982, Interleukin 1 and T cell activation, Immunol. Rev. 63:51–60.PubMedCrossRefGoogle Scholar
  38. 38.
    Mitchell, M. S., Kirkpatrick, D., Birnbaum-Mokyr, M., and Gery, I., 1973, On the mode of action of BCG, Nature New Biol. 243:216–228.PubMedCrossRefGoogle Scholar
  39. 39.
    Mustafa, A. S., and Godal, T., 1983, In vitro induction of human suppressor T cells by mycobacterial antigens. BCG-activated OKT4+ cells mediate suppression of antigen-induced T cell proliferation, Clin. Exp. Immunol. 52:29–37.PubMedGoogle Scholar
  40. 40.
    Mustafa, A. S., and Godal, T., 1985, BCG-induced suppressor T-cells: Optimal conditions for in vitro induction and mode of action, Clin. Exp. Immunol. 62:474–481.PubMedGoogle Scholar
  41. 41.
    Gardner, J. D., Ousley, M., Godfrey, W., Lindsey, N. J., and Abdou, N. I., 1982, Mycobacterium fortuitum infection: Evidence of bactericidal defect due to hyperactive antigen-specific suppressor cells. Correction in vitro and in vivo by cholinergic agonist and indomethacin. Am. J. Med. 73:756–764.PubMedCrossRefGoogle Scholar
  42. 42.
    Godal, T. ,and Negassi, K., 1973, Subclinical infection in leprosy, Br. Med. J. 3:557– 559.PubMedCrossRefGoogle Scholar
  43. 43.
    Sheppard, C. C., 1962, The nasal excretion of Mycobacterium leprae in leprosy, Int. J. Lepr. 30: 10–16.Google Scholar
  44. 44.
    Fenner, F., Martin, S. P., and Pierce, S. P., 1949, The enumeration of viable tubercle bacilli in cultures and infected tissues, Ann. N.Y. Acad. Sci. 52:751–758.PubMedCrossRefGoogle Scholar
  45. 45.
    Rook, G. A. W., 1975, The potentiating mytogenic and inhibitory effect on lymphocytes in vitro of macrophages in the lymph nodes of mice “overloaded” with mycobacterial products, Clin. Exp. Immunol. 21: 163–169.PubMedGoogle Scholar
  46. 46.
    Bjune, G., and Barnetson, R. StC., 1976, Plasma factors in delayed-type hypersensitivity. Augmentation of lymphocyte responses in borderline leprosy reactions, Clin. Exp. Immunol. 26:397–403.PubMedGoogle Scholar
  47. 47.
    Abe, M., Izumi, S., Saito, T., and Mathur, S. K., 1976, Early serodiagnosis of leprosy by indirect imunofluorescence, Lepr. India 48:272–276.PubMedGoogle Scholar
  48. 48.
    Young, D. B., and Buchanan, T. M., 1983, A serological test for leprosy with a glycolipid specific for Mycobacterium leprae, Science 221:1057–1059.PubMedCrossRefGoogle Scholar
  49. 49.
    Chakarvartti, M. R., and Vogel, F., 1973, A twin study in leprosy, in: Topics in Human Genetics ,Vol. 1, pp. 1–123. Thieme, Stuttgart.Google Scholar
  50. 50.
    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
  51. 51.
    Hunter, S. W., Fugiwara, 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
  52. 52.
    Taylor, C. E., Stashak, P. W., Caldes, G., Prescott, B., Chused, T. E., Brooks, A., and Baker, P. J., 1983, Activation of antigen-specific suppressor T cells by B cells from mice immunized with type III pneumococcal polysaccharide, J. Exp. Med. 158:703–717.PubMedCrossRefGoogle Scholar
  53. 53.
    Van Voorhis, W. C., Kaplan, G., Sarno, E. N., Horwitz, M. A., Steinman, R. M., Levis, W. R., Nogueira, N., Nair, L. S., Gattass, C. R., Arrick, B. A., and Cohn, Z. A., 1982, The cutaneous infiltrates of leprosy. Cellular characteristics and the predominant T cell phenotypes, N. Engl. J. Med. 307:1593–1597.PubMedCrossRefGoogle Scholar
  54. 54.
    Modlin, R. L., Hofman, F. M., Taylor, C. R., and Rean, T. H., 1983, T lymphocyte-subsets in the skin lesions of patients with leprosy, J. Am. Acad. Dermatol. 8: 181–189.Google Scholar
  55. 55.
    Guilberg, M., and Larsson, E. L., 1982, Studies on the induction and effector functions of concanavalin A-induced suppressor cells that limit TCGF production, J. Immunol. 128:747–750.Google Scholar
  56. 56.
    Kramer, M., and Koszinowski, U., 1982, T cell-specific supressor factor(s) with regulatory influence on interleukin 2 production and function, J. Immunol. 128:784–790.PubMedGoogle Scholar
  57. 57.
    Haregewoin, A., Godal, T., Mustafa, A. S., Belehu, A., and Yemaneberhan, T., 1983, T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosv, Nature (Lond.) 302:342–344.CrossRefGoogle Scholar
  58. 58.
    Nogueira, N., Kaplan, G., Levy, E., Sarno, E. N., Kushner, P., Granelli-Piperno, A., Vieira, L., Colomer Gould, V., Levis, W., Steinman, R., Yip, Y. K., and Cohn, Z. A. ,1983, Defective interferon production in leprosy. Reversal with antigen and interleukin 2,J. Exp. Med. 158:2165–2170.PubMedCrossRefGoogle Scholar
  59. 59.
    Nathan, C. F., Murray, H. W., Wiebe, M. E., and Rubin, B. Y., 1983, Identification of interferon- as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity, J. Exp. Med. 158:670–689.PubMedCrossRefGoogle Scholar
  60. 60.
    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
  61. 61.
    Convit, J., Aranzazu, N., Ulrich, M., Pinardi, M. E., Reyes, O., and Alvarado, J., 1982, Immunotherapy with a mixture of Mycobacterium leprae and BCG in different forms of leprosy and in Mitsuda-negative contacts, Int. J. Lepr. 50:415–424.Google Scholar
  62. 62.
    Convit. J., Pinardi, M. E., Rodriguez-Ochoa, G., Ulrich, M., Avila, J. L., and Goihman-Yahr, M., 1974, Elimination of Mycobacterium leprae subsequent to local in vivo activation of macrophages in lepromatous leprosy by other mycobacteria, Clin. Exp. Immunol. 17:261–265.PubMedGoogle Scholar
  63. 63.
    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
  64. 64.
    Mehra, V., Mason, L. H., Rothman, W., Reinherz, E., Schlossman, S. F., and Bloom, B. R., 1980, Delineation of a human T cell subset responsible for lepromin-induced suppression in leprosy patients, J. Immunol. 125:1183–1188.PubMedGoogle Scholar
  65. 65.
    Bloom, B. R., and Mehra, V., 1984, Immunological unresponsiveness in leprosy, Immunol. Rev. 80:5–28.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • S. Orbach-Arbouys
    • 1
  1. 1.Cancer and Immunogenetics InstitutePaul-Brousse HospitalVillejuifFrance

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