Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1985 Sep;56(1):141–151.

Effector mechanisms of syngeneic anti-tumour responses in mice. II. Cytotoxic T lymphocytes mediate neutralization and rejection of radiation-induced leukaemia RL male 1 in the nude mouse system.

A Keyaki, K Kuribayashi, S Sakaguchi, T Masuda, J Yamashita, H Handa, E Nakayama
PMCID: PMC1453675  PMID: 3876272

Abstract

We demonstrated the efficacy of a long-term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL male 1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CB6F1-nu/+ mouse immunized in vivo and RL male 1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL male 1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1:1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-1+23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 X 10(7) CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL male 1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL male 1 tumour cells and athymic nude mice.

Full text

PDF
141

Selected References

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

  1. Bernstein I. D. Passive transfer of systemic tumor immunity with cells generated in vitro by a secondary immune response to a syngeneic rat gross virus-induced lymphoma. J Immunol. 1977 Jan;118(1):122–128. [PubMed] [Google Scholar]
  2. Borberg H., Oettgen H. F., Choudry K., Beattie E. J., Jr Inhibition of established transplants of chemically induced sarcomas in syngeneic mice by lymphocytes from immunized donors. Int J Cancer. 1972 Nov;10(3):539–547. doi: 10.1002/ijc.2910100312. [DOI] [PubMed] [Google Scholar]
  3. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  4. Dailey M. O., Fathman C. G., Butcher E. C., Pillemer E., Weissman I. Abnormal migration of T lymphocyte clones. J Immunol. 1982 May;128(5):2134–2136. [PubMed] [Google Scholar]
  5. Dallman M. J., Mason D. W., Webb M. The roles of host and donor cells in the rejection of skin allografts by T cell-deprived rats injected with syngeneic T cells. Eur J Immunol. 1982 Jun;12(6):511–518. doi: 10.1002/eji.1830120612. [DOI] [PubMed] [Google Scholar]
  6. Donohue J. H., Rosenberg S. A. The fate of interleukin-2 after in vivo administration. J Immunol. 1983 May;130(5):2203–2208. [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. 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]
  9. Engers H. D., Glasebrook A. L., Sorenson G. D. Allogeneic tumor rejection induced by the intravenous injection of Lyt-2+ cytolytic T lymphocyte clones. J Exp Med. 1982 Oct 1;156(4):1280–1285. doi: 10.1084/jem.156.4.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Engers H. D., Lahaye T., Sorenson G. D., Glasebrook A. L., Horvath C., Brunner K. T. Functional activity in vivo of effector T cell populations. II. Anti-tumor activity exhibited by syngeneic anti-MoMULV-specific cytolytic T cell clones. J Immunol. 1984 Sep;133(3):1664–1670. [PubMed] [Google Scholar]
  11. Fernandez-Cruz E., Woda B. A., Feldman J. D. Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes. J Exp Med. 1980 Oct 1;152(4):823–841. doi: 10.1084/jem.152.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fujiwara H., Fukuzawa M., Yoshioka T., Nakajima H., Hamaoka T. The role of tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. I. Lyt-1+2- T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity. J Immunol. 1984 Sep;133(3):1671–1676. [PubMed] [Google Scholar]
  13. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  14. Gillis S., Union N. A., Baker P. E., Smith K. A. The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. J Exp Med. 1979 Jun 1;149(6):1460–1476. doi: 10.1084/jem.149.6.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giorgi J. V., Warner N. L. Continuous cytotoxic T cell lines reactive against murine plasmacytoma tumor-associated antigens. J Immunol. 1981 Jan;126(1):322–330. [PubMed] [Google Scholar]
  16. Greenberg P. D., Cheever M. A., Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med. 1981 Sep 1;154(3):952–963. doi: 10.1084/jem.154.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hardt C., Röllinghoff M., Pfizenmaier K., Mosmann H., Wagner H. Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo. J Exp Med. 1981 Aug 1;154(2):262–274. doi: 10.1084/jem.154.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kim B., Rosenstein M., Weiland D., Eberlein T. J., Rosenberg S. A. Clonal analysis of the lymphoid cells mediating skin allograft rejection. Mediation of graft rejection in vivo by cloned Lyt-1+2- proliferative, noncytotoxic long-term cell lines. Transplantation. 1983 Nov;36(5):525–532. doi: 10.1097/00007890-198311000-00011. [DOI] [PubMed] [Google Scholar]
  19. Kuribayashi K., Keyaki A., Sakaguchi S., Masuda T. Effector mechanisms of syngeneic anti-tumour responses in mice. I. Establishment and characterization of an exogenous IL-2-independent cytotoxic T-lymphocyte line specific for radiation-induced leukaemia RL male 1. Immunology. 1985 Sep;56(1):127–140. [PMC free article] [PubMed] [Google Scholar]
  20. LeFrancois L., Bevan M. J. A reexamination of the role of LYT-2-positive T cells in murine skin graft rejection. J Exp Med. 1984 Jan 1;159(1):57–67. doi: 10.1084/jem.159.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lotze M. T., Line B. R., Mathisen D. J., Rosenberg S. A. The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): implications for the adoptive immunotherapy of tumors. J Immunol. 1980 Oct;125(4):1487–1493. [PubMed] [Google Scholar]
  22. Loveland B. E., Hogarth P. M., Ceredig R., McKenzie I. F. Cells mediating graft rejection in the mouse. I. Lyt-1 cells mediate skin graft rejection. J Exp Med. 1981 May 1;153(5):1044–1057. doi: 10.1084/jem.153.5.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Loveland B. E., McKenzie I. F. Which T cells cause graft rejection? Transplantation. 1982 Mar;33(3):217–221. doi: 10.1097/00007890-198203000-00001. [DOI] [PubMed] [Google Scholar]
  24. Nakayama E., Shiku H., Stockert E., Oettgen H. F., Old L. J. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1977–1981. doi: 10.1073/pnas.76.4.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nakayama E., Shiku H., Takahashi T., Oettgen H. F., Old L. J. Definition of a unique cell surface antigen of mouse leukemia RL male 1 by cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3486–3490. doi: 10.1073/pnas.76.7.3486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Palladino M. A., Obata Y., Stockert E., Oettgen H. F. Characterization of interleukin 2-dependent cytotoxic T-cell clones: specificity, cell surface phenotype, and susceptibility to blocking by Lyt antisera. Cancer Res. 1983 Feb;43(2):572–576. [PubMed] [Google Scholar]
  28. Palladino M. A., Welte K., Carroll A. M., Oettgen H. F. Characterization of interleukin 2 (IL-2)-dependent cytotoxic T-cell clones. V. Transfer of resistance to allografts and tumor grafts requires exogenous IL-2. Cell Immunol. 1984 Jul;86(2):299–307. doi: 10.1016/0008-8749(84)90384-8. [DOI] [PubMed] [Google Scholar]
  29. Rosenberg S. A., Terry W. D. Passive immunotherapy of cancer in animals and man. Adv Cancer Res. 1977;25:323–388. doi: 10.1016/s0065-230x(08)60637-5. [DOI] [PubMed] [Google Scholar]
  30. Sakaguchi S., Takahashi T., Nishizuka Y. Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. J Exp Med. 1982 Dec 1;156(6):1565–1576. doi: 10.1084/jem.156.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sato H., Boyse E. A., Aoki T., Iritani C., Old L. J. Leukemia-associated transplantation antigens related to murine leukemia virus. The X.1 system: immune response controlled by a locus linked to H-2. J Exp Med. 1973 Sep 1;138(3):593–606. doi: 10.1084/jem.138.3.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WINN H. J. Immune mechanisms in homotransplantation. II. Quantitative assay of the immunologic activity of lymphoid cells stimulated by tumor homografts. J Immunol. 1961 Feb;86:228–239. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES