Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 May 1;159(5):1295–1311. doi: 10.1084/jem.159.5.1295

Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells

PMCID: PMC2187300  PMID: 6232335

Abstract

It was shown that the progressive growth of the immunogenic meth A fibrosarcoma in its semisyngeneic host results in the generation of concomitant immunity to the growth of a tumor implant. The generation of immunity occurred between days 6 and 9 of tumor growth and was associated with the generation of sensitized T cells that were capable, on passive transfer, of causing regression of a 3-d tumor in gamma- irradiated recipients. After day 9 of tumor growth, concomitant immunity and the T cells able to passively transfer it were progressively lost, and this was associated with the generation of splenic suppressor T cells able to suppress the expression of adoptive immunity against an established tumor in T cell-deficient ( TXB ) recipients. The T cells that passively transferred concomitant immunity were shown to be of the Ly-1-2+ phenotype, in contrast to the T cells that transferred suppression, which were shown with the same reagents to be Ly-1+2-. The results are consistent with the hypothesis that the progressive growth of an immunogenic tumor results in the generation of Ly-1-2+-sensitized effector T cells that fail to reach a number sufficient to destroy the tumor because their generation is down- regulated by tumor-induced Ly-1+2- suppressor T cells.

Full Text

The Full Text of this article is available as a PDF (957.7 KB).

Selected References

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

  1. Asano Y., Hodes R. J. T cell regulation of b cell activation. Cloned Lyt-1+2-T suppressor cells inhibit the major histocompatibility complex-restricted interaction of T helper cells with B cells and/or accessory cells. J Exp Med. 1983 Oct 1;158(4):1178–1190. doi: 10.1084/jem.158.4.1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benacerraf B., Greene M. I., Sy M. S., Dorf M. E. Suppressor T cell circuits. Ann N Y Acad Sci. 1982;392:300–308. doi: 10.1111/j.1749-6632.1982.tb36115.x. [DOI] [PubMed] [Google Scholar]
  3. Berendt M. J., North R. J. T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med. 1980 Jan 1;151(1):69–80. doi: 10.1084/jem.151.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonventre P. F., Nickol A. D., Ball E. J., Michael J. G., Bubel H. C. Development of protective immunity against bacterial and viral infections in tumor-bearing mice coincident with suppression of tumor immunity. J Reticuloendothel Soc. 1982 Jul;32(1):25–35. [PubMed] [Google Scholar]
  5. Cantor H., Shen F. W., Boyse E. A. Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1391–1340. doi: 10.1084/jem.143.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drebin J. A., Perry L. L., Carter R., Greene M. I. Regulation of the immune response to antigens on the malignant cell surface. Springer Semin Immunopathol. 1982;5(2):175–192. doi: 10.1007/BF00199795. [DOI] [PubMed] [Google Scholar]
  7. Duprez V., Hamilton B., Burakoff S. J. Generation of cytolytic T lymphocytes in thymectomized, irradiated, and bone marrow-reconstituted mice. J Exp Med. 1982 Sep 1;156(3):844–859. doi: 10.1084/jem.156.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dye E. S., North R. J., Mills C. D. Mechanisms of anti-tumor action of Corynebacterium parvum. I. Potentiated tumor-specific immunity and its therapeutic limitations. J Exp Med. 1981 Sep 1;154(3):609–620. doi: 10.1084/jem.154.3.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dye E. S., North R. J. T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med. 1981 Oct 1;154(4):1033–1042. doi: 10.1084/jem.154.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eberlein T. J., Rosenstein M., Rosenberg S. A. Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. J Exp Med. 1982 Aug 1;156(2):385–397. doi: 10.1084/jem.156.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elmets C. A., Bergstresser P. R., Tigelaar R. E., Wood P. J., Streilein J. W. Analysis of the mechanism of unresponsiveness produced by haptens painted on skin exposed to low dose ultraviolet radiation. J Exp Med. 1983 Sep 1;158(3):781–794. doi: 10.1084/jem.158.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gershon R. K. Immunoregulation circa 1980: some comments on the state of the art. J Allergy Clin Immunol. 1980 Jul;66(1):18–24. doi: 10.1016/0091-6749(80)90133-5. [DOI] [PubMed] [Google Scholar]
  13. Gorelik E. Concomitant tumor immunity and the resistance to a second tumor challenge. Adv Cancer Res. 1983;39:71–120. doi: 10.1016/s0065-230x(08)61033-7. [DOI] [PubMed] [Google Scholar]
  14. Greene M. I. The genetic and cellular basis of regulation of the immune response to tumor antigens. Contemp Top Immunobiol. 1980;11:81–116. doi: 10.1007/978-1-4684-3701-0_2. [DOI] [PubMed] [Google Scholar]
  15. Holán V., Mitchison N. A. Haplotype-specific suppressor T cells mediating linked suppression of immune responses elicited by third-party H-2 alloantigens. Eur J Immunol. 1983 Aug;13(8):652–657. doi: 10.1002/eji.1830130809. [DOI] [PubMed] [Google Scholar]
  16. Leclerc J. C., Cantor H. T cell-mediated immunity to oncornavirus-induced tumors. II. Ability of different T cell sets to prevent tumor growth in vivo. J Immunol. 1980 Feb;124(2):851–854. [PubMed] [Google Scholar]
  17. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  18. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liew F. Y., Hale C., Howard J. G. Immunologic regulation of experimental cutaneous leishmaniasis. V. Characterization of effector and specific suppressor T cells. J Immunol. 1982 Apr;128(4):1917–1922. [PubMed] [Google Scholar]
  20. Loveland B. E., McKenzie I. F. Cells mediating graft rejection in the mouse. III. Ly-1+ precursor T cells generate skin graft rejection. Transplantation. 1982 Apr;33(4):407–410. doi: 10.1097/00007890-198204000-00013. [DOI] [PubMed] [Google Scholar]
  21. Macphail S., Stutman O. Suppressor T cells activated in a primary in vitro response to non-major histocompatibility alloantigens. J Exp Med. 1982 Nov 1;156(5):1398–1414. doi: 10.1084/jem.156.5.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mills C. D., North R. J. Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient. Inhibition by suppressor T cells. J Exp Med. 1983 May 1;157(5):1448–1460. doi: 10.1084/jem.157.5.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Naor D. Suppressor cells: permitters and promoters of malignancy? Adv Cancer Res. 1979;29:45–125. doi: 10.1016/s0065-230x(08)60846-5. [DOI] [PubMed] [Google Scholar]
  24. North R. J. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med. 1982 Apr 1;155(4):1063–1074. doi: 10.1084/jem.155.4.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. North R. J., Kirstein D. P. T-cell-mediated concomitant immunity to syngeneic tumors. I. Activated macrophages as the expressors of nonspecific immunity to unrelated tumors and bacterial parasites. J Exp Med. 1977 Feb 1;145(2):275–292. doi: 10.1084/jem.145.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Prowse S. J., Warren H. S., Agostino M., Lafferty K. J. Transfer of sensitised Lyt 2+ cells triggers acute rejection of pancreatic islet allografts. Aust J Exp Biol Med Sci. 1983 Apr;61(Pt 2):181–185. doi: 10.1038/icb.1983.16. [DOI] [PubMed] [Google Scholar]
  27. Rolink A. G., Gleichmann E. Allosuppressor- and allohelper-T cells in acute and chronic graft-vs.-host (GVH) disease. III. Different Lyt subsets of donor T cells induce different pathological syndromes. J Exp Med. 1983 Aug 1;158(2):546–558. doi: 10.1084/jem.158.2.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WINN H. J. The immune response and the homograft reaction. Natl Cancer Inst Monogr. 1960 Mar;2:113–138. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES