Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1978 Sep;38(3):365–374. doi: 10.1038/bjc.1978.216

Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas.

G Y Gillespie, C B Hansen, S W Russell
PMCID: PMC2009749  PMID: 81673

Abstract

We have previously documented the development and subsequent disappearance of cytolytic activity mediated by lymphocytes from lymph nodes draining Moloney sarcomas destined either to regress or grow progressively. We now report that these tumour-draining lymphnode cells (LNC) that were no longer cytotoxic, spontaneously regenerated peak levels of killing after culture in vitro for 4 days in the absence of exogenous tumour antigen. Cytolytic activity, which was antigenically specific, was mediated by T lymphocytes. Resurgence of cytolytic activity in vitro was accompanied by proliferative changes (DNA synthesis, blast transformation, cell division) which peaked on the 3rd day of culture. Although normal, nonimmune LNC underwent quantitatively similar proliferative changes in culture, the killing that developed was weak and antigenically nonspecific. Transfer of cultured, tumour-draining LNC to immunologically compromised, syngeneic mice conferred complete protection from Moloney sarcoma progression. Adoptive transfer could be delayed for 6 days after tumour induction without loss of protection. These results suggest that there exists in Moloney sarcoma-bearing mice a mechanism that limits the differentiation of pre-killer cells into cytolytically active T lymphocytes, and that such inhibition is eliminated when LNC are explanted into culture.

Full text

PDF
365

Selected References

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

  1. Alexander P., Bensted J., Delorme E. J., Hall J. G., Hodgett J. The cellular immune response to primary sarcomata in rats. II. Abnormal responses of nodes draining the tumour. Proc R Soc Lond B Biol Sci. 1969 Nov 18;174(1035):237–251. doi: 10.1098/rspb.1969.0090. [DOI] [PubMed] [Google Scholar]
  2. Baldwin R. W., Price M. R., Robins R. A. Inhibition of hepatoma-immune lymph-node cell cytotoxicity by tumour-bearer serum, and solubilized hepatoma antigen. Int J Cancer. 1973 May;11(3):527–535. doi: 10.1002/ijc.2910110304. [DOI] [PubMed] [Google Scholar]
  3. Currie G. A., Basham C. Serum mediated inhibition of the immunological reactions of the patient to his own tumour: a possible role for circulating antigen. Br J Cancer. 1972 Dec;26(6):427–438. doi: 10.1038/bjc.1972.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Djeu J. Y., Glaser M., Huang K. Y., Herberman R. B. Participation of three lymphoid cell types in the in vitro activation of cell-mediated immunity to a syngeneic gross virus-induced lymphoma in rats. Cell Immunol. 1976 May;23(2):268–277. doi: 10.1016/0008-8749(76)90192-1. [DOI] [PubMed] [Google Scholar]
  5. Fujimoto S., Greene M. I., Sehon A. H. Regualtion of the immune response to tumor antigens. I. Immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976 Mar;116(3):791–799. [PubMed] [Google Scholar]
  6. Gillespie G. Y., Hansen C. B., Hoskins R. G., Russell S. W. Inflammatory cells in solid murine neoplasms. IV. Cytolytic T lymphocytes isolated from regressing or progressing Moloney sarcomas. J Immunol. 1977 Aug;119(2):564–570. [PubMed] [Google Scholar]
  7. Gillespie G. Y., Russell S. W. Development and persistence of cytolytic T lymphocytes in regressing or progressing Moloney sarcomas. Int J Cancer. 1978 Jan 15;21(1):94–99. doi: 10.1002/ijc.2910210116. [DOI] [PubMed] [Google Scholar]
  8. Holden H. T., Haskill J. S., Kirchner H., Herberman R. B. Two functionally distinct anti-tumor effector cells isolated from primary murine sarcoma virus-induced tumors. J Immunol. 1976 Aug;117(2):440–446. [PubMed] [Google Scholar]
  9. Kamat R., Henney C. S. Studies on T cell clonal expansion. I. Suppression of killer T cell production in vivo. J Immunol. 1975 Dec;115(6):1592–1598. [PubMed] [Google Scholar]
  10. Kamat R., Henney C. S. Studies on T cell clonal expansion. II. The in vitro differentiation of pre-killer and memory T cells. J Immunol. 1976 May;116(5):1490–1495. [PubMed] [Google Scholar]
  11. Kamo I., Friedman H. Immunosuppression and the role of suppressive factors in cancer. Adv Cancer Res. 1977;25:271–321. doi: 10.1016/s0065-230x(08)60636-3. [DOI] [PubMed] [Google Scholar]
  12. Kedar E., Ortiz de Landazuri M., Bonavida B. Cellular immunoadsorbents: a simplified technique for separation of lymphoid cell populations. J Immunol. 1974 Mar;112(3):1231–1243. [PubMed] [Google Scholar]
  13. Kirchner H., Chused T. M., Herberman R. B., Holden H. T., Lavrin D. H. Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by Moloney sarcoma virus. J Exp Med. 1974 Jun 1;139(6):1473–1487. doi: 10.1084/jem.139.6.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kuperman O., Fortner G. W., Lucas Z. J. Immune response to a syngeneic mammary adenocarcinoma. III. Development of memory and suppressor functions modulating cellular cytotoxicity. J Immunol. 1975 Nov;115(5):1282–1287. [PubMed] [Google Scholar]
  15. Laux D., Lausch R. N. Reversal of tumor-mediated suppression of immune reactivity by in vitro incubation of spleen cells. J Immunol. 1974 May;112(5):1900–1908. [PubMed] [Google Scholar]
  16. MacDonald H. R., Cerottini J. C., Brunner K. T. Generation of cytotoxic T lymphocytes in vitro. III. Velocity sedimentation studies of the differentiation and fate of effector cells in long-term mixed leukocyte cultures. J Exp Med. 1974 Dec 1;140(6):1511–1521. doi: 10.1084/jem.140.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Macdonald H. R., Engers H. D., Cerottini J. C., Brunner K. T. Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):718–730. doi: 10.1084/jem.140.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ortiz de Landazuri M., Herberman R. B. In vitro activation of cellular immune response to Gross virus-induced lymphoma. J Exp Med. 1972 Nov 1;136(5):969–983. doi: 10.1084/jem.136.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parkhouse R. M., Dutton R. W. Inhibition of spleen cell DNA synthesis by autologous macrophages. J Immunol. 1966 Nov;97(5):663–669. [PubMed] [Google Scholar]
  20. Plata F., MacDonald H. R., Sordat B. Studies on the distribution and origin of cytolytic T lymphocytes present in mice bearing Moloney murine sarcoma virus (MSV)-induced tumors. Bibl Haematol. 1975 Oct;(43):274–277. doi: 10.1159/000399147. [DOI] [PubMed] [Google Scholar]
  21. Russell S. W., Cochrane C. G. The cellular events associated with regression and progression of murine (Moloney) sarcomas. Int J Cancer. 1974 Jan 15;13(1):54–63. doi: 10.1002/ijc.2910130107. [DOI] [PubMed] [Google Scholar]
  22. Russell S. W., Doe W. F., Hoskins R. G., Cochrane C. G. Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. Int J Cancer. 1976 Sep 15;18(3):322–330. doi: 10.1002/ijc.2910180309. [DOI] [PubMed] [Google Scholar]
  23. Russell S. W., Gillespie G. Y., Hansen C. B., Cochrane C. G. Inflammatory cells in solid murine neoplasms. II. Cell types found throughout the course of Moloney sarcoma regression or progression. Int J Cancer. 1976 Sep 15;18(3):331–338. doi: 10.1002/ijc.2910180310. [DOI] [PubMed] [Google Scholar]
  24. Röllinghoff M., Starzinski-Powitz A., Pfizenmaier K., Wagner H. Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes. J Exp Med. 1977 Feb 1;145(2):455–459. doi: 10.1084/jem.145.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Starzinski-Powitz A., Pfizenmaier K., Röllinghoff M., Wagner H. In vivo sensitization of T cells to hapten-conjugated syngeneic structures of major histocompatibility complex. I. Effect of in vitro culture upon generation of cytotoxic T lymphocytes. Eur J Immunol. 1976 Nov;6(11):799–805. doi: 10.1002/eji.1830061109. [DOI] [PubMed] [Google Scholar]
  26. Sudo H., Hashimoto Y. Enhancement of cytotoxic activity of immune peritoneal lymphocytic cells against antigenic tumor cells after in vitro culture. Gan. 1971 Aug;62(4):275–281. [PubMed] [Google Scholar]
  27. Takei F., Levy J. G., Kilburn D. G. Characterization of suppressor cells in mice bearing syngeneic mastocytoma. J Immunol. 1977 Feb;118(2):412–417. [PubMed] [Google Scholar]
  28. Wing E. J., Remington J. S. Studies on the regulation of lymphocyte reactivity by normal and activated macrophages. Cell Immunol. 1977 Apr;30(1):108–121. doi: 10.1016/0008-8749(77)90052-1. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES