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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 Jul 1;138(1):1–15. doi: 10.1084/jem.138.1.1

IN VITRO INDUCTION OF TUMOR-SPECIFIC IMMUNITY

I. PARAMETERS OF ACTIVATION AND CYTOTOXIC REACTIVITY OF MOUSE LYMPHOID CELLS IMMUNIZED IN VITRO AGAINST SYNGENEIC AND ALLOGENEIC PLASMA CELL TUMORS

Hermann Wagner 1, Martin Röllinghoff 1
PMCID: PMC2180543  PMID: 4541509

Abstract

Induction of tumor-specific immunity in vitro was accomplished by cocultivation of cortisone-resistant murine thymocytes or spleen cells with irradiated syngeneic plasma cell tumors (PCT). The cytotoxic activity generated could be detected in a short-term 51Cr-release assay. Optimal cytotoxic activity against PCT-associated transplantation antigens (TATA) was generated after 7 days in culture. Unlike cytotoxic responses to tumor allografts in which the cytotoxic activity was directed against allogeneic transplantation antigens, the cytotoxic activity obtained in the syngeneic tumor system was specific to the immunizing syngeneic PCT. Similar parameters of induction of cytotoxic responses in in vitro tumor allograft responses and in the syngeneic tumor system suggested that both reactions are cell-mediated cytotoxic immune responses. With regard to the magnitude of cytotoxic responses obtained, allogeneic transplantation antigens induced about a 30-fold higher cytotoxic immune response than plasma cell TATA. The results are consistent with the concept that in vitro tumor allograft responses and in vitro responses against TATA of PCT are similar in quality, but differ in the magnitude of the cytotoxic response provoked.

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Selected References

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  1. BURNET M. Cancer; a biological approach. I. The processes of control. Br Med J. 1957 Apr 6;1(5022):779–786. doi: 10.1136/bmj.1.5022.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bloom B. R., Bennett B., Oettgen H. F., McLean E. P., Old L. J. Demonstration of delayed hypersensitivity to soluble antigens of chemically induced tumors by inhibition of macrophage migration. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1176–1180. doi: 10.1073/pnas.64.4.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brunner K. T., Mauel J., Rudolf H., Chapuis B. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970 Apr;18(4):501–515. [PMC free article] [PubMed] [Google Scholar]
  4. Churchill W. H., Jr, Rapp H. J., Kronman B. S., Borsos T. Detection of antigens of a new diethylnitrosamine-induced transplantable hepatoma by delayed hypersensitivity. J Natl Cancer Inst. 1968 Jul;41(1):13–29. [PubMed] [Google Scholar]
  5. DUNN T. B., POTTER M. A transplantable mast-cell neoplasm in the mouse. J Natl Cancer Inst. 1957 Apr;18(4):587–601. [PubMed] [Google Scholar]
  6. Diener E., Armstrong W. D. Immunological tolerance in vitro: kinetic studies at the cellular level. J Exp Med. 1969 Mar 1;129(3):591–603. doi: 10.1084/jem.129.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans R., Alexander P. Cooperation of immune lymphoid cells with macrophages in tumour immunity. Nature. 1970 Nov 14;228(5272):620–622. doi: 10.1038/228620a0. [DOI] [PubMed] [Google Scholar]
  8. FOLEY E. J. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953 Dec;13(12):835–837. [PubMed] [Google Scholar]
  9. GORER P. A., AMOS D. B. Passive immunity in mice against C57BL leukosis E.L. 4 by means of iso-immune serum. Cancer Res. 1956 May;16(4):338–343. [PubMed] [Google Scholar]
  10. HANKS J. H., WALLACE J. H. Determination of cell viability. Proc Soc Exp Biol Med. 1958 May;98(1):188–192. doi: 10.3181/00379727-98-23985. [DOI] [PubMed] [Google Scholar]
  11. Halliday W. J. Blocking effect of serum from tumor-bearing animals on macrophage migration inhibition with tumor antigens. J Immunol. 1971 Mar;106(3):855–857. [PubMed] [Google Scholar]
  12. Hellström I. E., Hellström K. E., Pierce G. E., Bill A. H. Demonstration of cell-bound and humoral immunity against neuroblastoma cells. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1231–1238. doi: 10.1073/pnas.60.4.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. KLEIN G., SJOGREN H. O., KLEIN E., HELLSTROM K. E. Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res. 1960 Dec;20:1561–1572. [PubMed] [Google Scholar]
  14. Kikuchi K., Kikuchi Y., Phillips M. E., Southam C. M. Tumor-specific, cell-mediated immune resistance to autochthonous tumors. Cancer Res. 1972 Mar;32(3):516–521. [PubMed] [Google Scholar]
  15. Law L. W. Studies of tumor antigens and tumor-specific immune mechanisms in experimental systems. Transplant Proc. 1970 Mar;2(1):117–132. [PubMed] [Google Scholar]
  16. Marbrook J. Primary immune response in cultures of spleen cells. Lancet. 1967 Dec 16;2(7529):1279–1281. doi: 10.1016/s0140-6736(67)90393-5. [DOI] [PubMed] [Google Scholar]
  17. Miller J. F., Sprent J. Cell-to-cell interaction in the immune response. VI. Contribution of thymus-derived cells and antibody-forming cell precursors to immunological memory. J Exp Med. 1971 Jul 1;134(1):66–82. doi: 10.1084/jem.134.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oettgen H. F., Old L. J., McLean E. P., Carswell E. A. Delayed hypersensitivity and transplantation immunity elicited by soluble antigens of chemically induced tumours in inbred guinea-pigs. Nature. 1968 Oct 19;220(5164):295–297. doi: 10.1038/220295a0. [DOI] [PubMed] [Google Scholar]
  19. PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
  20. Röllinghoff M., Rouse B. T., Warner N. L. Tumor immunity to murine plasma cell tumors. I. Tumor-associated transplantation antigens of NZB and BALB-c plasma cell tumors. J Natl Cancer Inst. 1973 Jan;50(1):159–172. doi: 10.1093/jnci/50.1.159. [DOI] [PubMed] [Google Scholar]
  21. Stjernswärd J., Almgård L. E., Franzén S., von Schreeb T., Wadström L. B. Tumour-distinctive cellular immunity to renal carcinoma. Clin Exp Immunol. 1970 Jun;6(6):963–968. [PMC free article] [PubMed] [Google Scholar]
  22. Vaage J., Jones R. D., Brown B. W. Tumor-specific resistance in mice detected by inhibition of macrophage migration. Cancer Res. 1972 Apr;32(4):680–687. [PubMed] [Google Scholar]
  23. Wagner H. Cell-mediated immune response in vitro. IV. Metabolic studies on cellular immunogenicity. Eur J Immunol. 1973 Feb;3(2):84–89. doi: 10.1002/eji.1830030206. [DOI] [PubMed] [Google Scholar]
  24. Wagner H., Feldmann M. Cell-mediated immune response in vitro. I. A new in vitro system for the generation of cell-mediated cytotoxic activity. Cell Immunol. 1972 Mar;3(3):405–420. doi: 10.1016/0008-8749(72)90246-8. [DOI] [PubMed] [Google Scholar]
  25. Wagner H., Harris A. W., Feldmann M. Cell-mediated immune response in vitro. II. The role of thymus and thymus-derived lymphocytes. Cell Immunol. 1972 May;4(1):39–50. doi: 10.1016/0008-8749(72)90004-4. [DOI] [PubMed] [Google Scholar]
  26. Wagner H. The correlation between the proliferative and the cytotoxic responses of mouse lymphocytes to allogeneic cells in vitro. J Immunol. 1972 Sep;109(3):630–637. [PubMed] [Google Scholar]
  27. Wilson D. B. Quantitative studies on the mixed lymphocyte interaction in rats. I. Conditions and parameters of response. J Exp Med. 1967 Oct 1;126(4):625–654. doi: 10.1084/jem.126.4.625. [DOI] [PMC free article] [PubMed] [Google Scholar]

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