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. 1985 Oct;56(2):235–243.

Effect of Bacillus Calmette-Guérin on the in vitro generation of cytotoxic T lymphocytes. II. Role of interleukin-1-like factors and of soluble suppressor factors.

L Mellow, E Sabbadini
PMCID: PMC1453679  PMID: 2932383

Abstract

The injection of BCG vaccine in C57BL/6J mice results in the suppression of the generation of cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC) and of mitogenic reactions to concanavalin A (Con A). Suppression is mediated by macrophage-like suppressor cells. Since previous work had indicated that suppression involved the inhibition of the production of interleukin-2 (IL-2), the effects of BCG on interleukin-1 (IL-1), a monokine required for IL-2 production, were investigated. It was found that the release of IL-1-like activity in spleen cell cultures stimulated with LPS or Con A was increased by previous BCG treatment of the cell donors. In MLC, the release of IL-1-like activity was also increased by BCG. However, the detection of IL-1-like activity in MLC supernatants was prevented by the presence of a suppressor factor. In this case, the IL-1-like activity could be separated with gel filtration from the suppressor factor which had higher molecular weight. The production of IL-1-like activity by CBA/J spleen cells, which are not suppressed by BCG, was not significantly different from that of C57BL/6J cells, which are markedly suppressed. Moreover, the addition of IL-1 to the BCG-suppressed cultures not only did not restore normal reactivity, but actually further suppressed CTL formation. It was concluded that BCG-induced suppression cannot be attributed to decreased IL-1 activity. The suppressor factor discovered during these investigations may have a role in this type of suppression.

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Selected References

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

  1. Bullock W. E., Carlson E. M., Gershon R. K. The evolution of immunosuppressive cell populations in experimental mycobacterial infection. J Immunol. 1978 May;120(5):1709–1716. [PubMed] [Google Scholar]
  2. Castés M., Lynch N. R., Lespinats G., Orbach-Arbouys S. Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG. Br J Cancer. 1981 Dec;44(6):828–837. doi: 10.1038/bjc.1981.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Farrar J. J., Benjamin W. R., Hilfiker M. L., Howard M., Farrar W. L., Fuller-Farrar J. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–166. doi: 10.1111/j.1600-065x.1982.tb00414.x. [DOI] [PubMed] [Google Scholar]
  4. Farrar J. J., Koopman W. J., Fuller-Bonar J. Identification and partial purification of two synergistically acting helper mediators in human mixed leukocyte culture supernatants. J Immunol. 1977 Jul;119(1):47–54. [PubMed] [Google Scholar]
  5. Gery I., Gershon R. K., Waksman B. H. Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes. J Immunol. 1971 Dec;107(6):1778–1780. [PubMed] [Google Scholar]
  6. Green S., Dobrjansky A., Carswell E. A., Kassel R. L., Old L. J., Fiore N., Schwartz M. K. Partial purification of a serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1976 Feb;73(2):381–385. doi: 10.1073/pnas.73.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kendall L., Sabbadini E. Effect of Bacillus Calmette-Guérin 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. 1981 Jul;127(1):234–238. [PubMed] [Google Scholar]
  8. Klimpel G. R., Henney C. S. BCG-induced suppressor cells. I. Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro. J Immunol. 1978 Feb;120(2):563–569. [PubMed] [Google Scholar]
  9. Mitchell M. S., Kirkpatrick D., Mokyr M. B., Gery I. On the mode of action of BCG. Nat New Biol. 1973 Jun 13;243(128):216–218. doi: 10.1038/newbio243216a0. [DOI] [PubMed] [Google Scholar]
  10. Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
  11. Nelson D. S. Production by stimulated macrophages of factors depressing lymphocyte transformation. Nature. 1973 Nov 30;246(5431):306–307. doi: 10.1038/246306a0. [DOI] [PubMed] [Google Scholar]
  12. Ptak W., Zembala M., Gershon R. K. Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets. J Exp Med. 1978 Aug 1;148(2):424–434. doi: 10.1084/jem.148.2.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schrier D. J., Allen E. M., Moore V. L. BCG-induced macrophage suppression in mice: suppression of specific and nonspecific antibody-medicated and cellular immunologic responses. Cell Immunol. 1980 Dec;56(2):347–356. doi: 10.1016/0008-8749(80)90110-0. [DOI] [PubMed] [Google Scholar]
  14. Schrier D. J., Sternick J. L., Allen E. M., Moore V. L. Immunogenetics of BCG-induced anergy in mice: control by genes linked to the Igh complex. J Immunol. 1982 Mar;128(3):1466–1469. [PubMed] [Google Scholar]
  15. Scott M. T. Biological effects of the adjuvant Corynebacterium parvum. II. Evidence for macrophage-T-cell interaction. Cell Immunol. 1972 Nov;5(3):469–479. doi: 10.1016/0008-8749(72)90073-1. [DOI] [PubMed] [Google Scholar]
  16. Tadakuma T., Pierce C. W. Mode of action of a soluble immune response suppressor (SIRS) produced by concanavalin a-activated spleen cells. J Immunol. 1978 Feb;120(2):481–486. [PubMed] [Google Scholar]
  17. Turcotte R. Evidence for two distinct populations of suppressor cells in the spleens of Mycobacterium bovis BCG-Sensitized mice. Infect Immun. 1981 Nov;34(2):315–322. doi: 10.1128/iai.34.2.315-322.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Turcotte R., Lemieux S. Mechanisms of action of Mycobacterium bovis BCG-induced suppressor cells in mitogen-induced blastogenesis. Infect Immun. 1982 Apr;36(1):263–270. doi: 10.1128/iai.36.1.263-270.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wagner H., Hardt C., Heeg K., Pfizenmaier K., Solbach W., Bartlett R., Stockinger H., Röllinghoff M. 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. 1980;51:215–255. doi: 10.1111/j.1600-065x.1980.tb00323.x. [DOI] [PubMed] [Google Scholar]
  20. Waldman S. R., Gottlieb A. A. Macrophage regulation of DNA synthesis in lymphoid cells: effects of a soluble factor from macrophages. Cell Immunol. 1973 Oct;9(1):142–156. doi: 10.1016/0008-8749(73)90175-5. [DOI] [PubMed] [Google Scholar]

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