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. 1979 Dec 1;150(6):1367–1382. doi: 10.1084/jem.150.6.1367

In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses

PMCID: PMC2185727  PMID: 229187

Abstract

We have developed a system to induce oncornavirus-specific secondary cytotoxic response in vitro. When Moloney strain of murine sarcoma virus-immune spleen cells were cultivated with purified infectious Moloney murine leukemia virus (M-MuLV) or with supernates of tissue culture cells containing infectious virus, a virus-specific secondary cytotoxic response directed against type-specific determinant(s) of M- MuLV was generated in vitro, as determined by a 4-h 51Cr-release assay. The effector cells were susceptible to the treatment with anti-Thyl.2 plus complement, but were unrelated to natural killer cells (NK), because they could not lyse some target cells specific for M-MuLV in both the induction phase and the interaction between effector cells and target cells. Furthermore, a product of the env gene of M-MuLV, perhaps gp70, appeared to be responsible for this response, because viruses with recombinations in the env gene between ecotropic M-MuLV and a xenotropic virus failed to induce a response. When infectious M-MuLV was exposed to UV-light at different doses, the ability of UV-treated M- MuLV to induce a secondary cytotoxic response decreased in parallel with infectivity, indicating that infectivity was necessary for the induction of this response.

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Selected References

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  1. Alaba O., Law L. W. Secondary induction of cytotoxic T lymphocytes with solubilized syngeneic tumor cell plasma membranes. J Exp Med. 1978 Nov 1;148(5):1435–1439. doi: 10.1084/jem.148.5.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aoki T., Herberman R. B., Hartley J. W., Liu M., Walling M. J., Nunn M. Surface antigens on transplantable tumor cell lines producing mouse type C viruses. J Natl Cancer Inst. 1977 Apr;58(4):1069–1078. doi: 10.1093/jnci/58.4.1069. [DOI] [PubMed] [Google Scholar]
  3. Aoki T., Herberman R. B., Liu M. Heterogeneity of surface antigens on endogenous type C virus-producing cell sublines derived from a clonal line of BALB/3T3 cells. Intervirology. 1975;5(1-2):31–42. doi: 10.1159/000149878. [DOI] [PubMed] [Google Scholar]
  4. Bassin R. H., Tuttle N., Fischinger P. J. Isolation of murine sarcoma virus-transformed mouse cells which are negative for leukemia virus from agar suspension cultures. Int J Cancer. 1970 Jul 15;6(1):95–107. doi: 10.1002/ijc.2910060114. [DOI] [PubMed] [Google Scholar]
  5. Bassin R. H., Tuttle N., Fischinger P. J. Rapid cell culture assay technic for murine leukaemia viruses. Nature. 1971 Feb 19;229(5286):564–566. doi: 10.1038/229564b0. [DOI] [PubMed] [Google Scholar]
  6. Braciale T. J., Yap K. L. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med. 1978 Apr 1;147(4):1236–1252. doi: 10.1084/jem.147.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bruce J., Mitchison N. A., Shellam G. R. Studies on a gross-virus-induced lymphoma in the rat. III. Optimisation, specificity and applications of the in vitro immune response. Int J Cancer. 1976 Mar 15;17(3):342–350. doi: 10.1002/ijc.2910170310. [DOI] [PubMed] [Google Scholar]
  8. Cerny J., Essex M. Membrane antigens of murine leukaemia cells. Nature. 1974 Oct 25;251(5477):742–745. doi: 10.1038/251742a0. [DOI] [PubMed] [Google Scholar]
  9. Cloyd M. W., Bolognesi D. P., Bigner D. D. Immunofluorescent analysis of expression of the RNA tumor virus major glycoprotein, gp71, on surfaces of virus-producing murine and other mammalian species cell lines. Cancer Res. 1977 Mar;37(3):922–930. [PubMed] [Google Scholar]
  10. Enjuanes L., Lee J. C., Ihle J. N. Antigenic specificities of the cellular immune response of C57BL/6 mice to the Moloney leukemia/sarcoma virus complex. J Immunol. 1979 Feb;122(2):665–674. [PubMed] [Google Scholar]
  11. Finberg R., Mescher M., Burakoff S. J. The induction of virus-specific cytotoxic T lymphocytes with solubilized viral and membrane proteins. J Exp Med. 1978 Dec 1;148(6):1620–1627. doi: 10.1084/jem.148.6.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fischinger P. J., Blevins C. S., Nomura S. Simple, quantitative assay for both xenotropic murine leukemia and ecotropic feline leukemia viruses. J Virol. 1974 Jul;14(1):177–179. doi: 10.1128/jvi.14.1.177-179.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fischinger P. J., Frankel A. E., Elder J. H., Lerner R. A., Ihle J. N., Bolognesi D. P. Biological, immunological, and biochemical evidence that HIX virus is a recombinant between Moloney leukemia virus and a murine xenotropic C type virus. Virology. 1978 Oct 15;90(2):241–254. doi: 10.1016/0042-6822(78)90308-2. [DOI] [PubMed] [Google Scholar]
  14. Gomard E., Levy J. P., Plata F., Henin Y., Duprez V., Bismuth A., Reme T. Studies on the nature of the cell surface antigen reacting with cytolytic T lymphocytes in murine oncornavirus-induced tumors. Eur J Immunol. 1978 Apr;8(4):228–236. doi: 10.1002/eji.1830080403. [DOI] [PubMed] [Google Scholar]
  15. Hartley J. W., Rowe W. P. Clonal cells lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology. 1975 May;65(1):128–134. doi: 10.1016/0042-6822(75)90013-6. [DOI] [PubMed] [Google Scholar]
  16. Herberman R. B., Aoki T., Nunn M., Lavrin D. H., Soares N., Gazdar A., Holden H., Chang K. S. Specificity of 51Cr-release cytotoxicity of lymphocytes immune to murine sarcoma virus. J Natl Cancer Inst. 1974 Oct;53(4):1103–1111. doi: 10.1093/jnci/53.4.1103. [DOI] [PubMed] [Google Scholar]
  17. Herberman R. B. Cell-mediated immunity to tumor cells. Adv Cancer Res. 1974;19(0):207–263. doi: 10.1016/s0065-230x(08)60055-x. [DOI] [PubMed] [Google Scholar]
  18. Herberman R. B., Holden H. T. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305–377. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
  19. Herberman R. B., Nunn M. E., Lavrin D. H., Asofsky R. Effect of antibody to theta antigen on cell-mediated immunity induced in syngeneic mice by murine sarcoma virus. J Natl Cancer Inst. 1973 Nov;51(5):1509–1512. doi: 10.1093/jnci/51.5.1509. [DOI] [PubMed] [Google Scholar]
  20. Holden H. T., Landolfo S., Herberman R. B. T-cell-dependent reactivity against tumor-associated antigens on allogeneic target cells. Transplant Proc. 1977 Mar;9(1):1149–1152. [PubMed] [Google Scholar]
  21. Holden H. T., Oldham R. K., Ortaldo J. R., Herberman R. B. Standardization of the chromium-51 release, cell-mediated cytotoxicity assay: cryopreservation of mouse effector and target cells. J Natl Cancer Inst. 1977 Mar;58(3):611–622. doi: 10.1093/jnci/58.3.611. [DOI] [PubMed] [Google Scholar]
  22. Knight R. A., Gorczynski R. M. Cell-mediated immunity to moloney sarcoma virus in mice. I. Analysis of antigens responsible for lymphocyte stimulation in regressor mice. Int J Cancer. 1975 Jan 15;15(1):48–58. doi: 10.1002/ijc.2910150107. [DOI] [PubMed] [Google Scholar]
  23. Lamon E. W., Skurzak H. M., Klein E. The lymphocyte response to a primary viral neoplasm (MSV) through its entire course in BALB-c mice. Int J Cancer. 1972 Nov;10(3):581–588. doi: 10.1002/ijc.2910100317. [DOI] [PubMed] [Google Scholar]
  24. Lavrin D. H., Herberman R. B., Nunn M., Soares N. In vitro cytotoxicity studies of murine sarcoma virus-induced immunity in mice. J Natl Cancer Inst. 1973 Nov;51(5):1497–1508. doi: 10.1093/jnci/51.5.1497. [DOI] [PubMed] [Google Scholar]
  25. Leclerc J. C., Gomard E., Levy J. P. Cell-mediated reaction against tumors induced by oncornaviruses. I. Kinetics and specificity of the immune response in murine sarcoma virus (MSV)-induced tumors and transplanted lymphomas. Int J Cancer. 1972 Nov;10(3):589–601. doi: 10.1002/ijc.2910100318. [DOI] [PubMed] [Google Scholar]
  26. Levy J. P., Leclerc J. C. The murine sarcoma virus-induced tumor: exception or general model in tumor immunology? Adv Cancer Res. 1977;24:1–66. doi: 10.1016/s0065-230x(08)61012-x. [DOI] [PubMed] [Google Scholar]
  27. Ng A. K., McIntire R., Holden H. T., Herberman R. B. Serologic analysis of tumor-associated surface antigens on a Moloney leukemia virus-induced lymphoma, MBL-2. J Immunol. 1978 Sep;121(3):856–862. [PubMed] [Google Scholar]
  28. Peebles P. T. An in vitro focus-induction assay for xenotropic murine leukemia virus, feline leukemia virus C, and the feline--primate viruses RD-114/CCC/M-7. Virology. 1975 Sep;67(1):288–291. doi: 10.1016/0042-6822(75)90427-4. [DOI] [PubMed] [Google Scholar]
  29. Plata F., Cerottini J. C., Brunner K. T. Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Eur J Immunol. 1975 Apr;5(4):227–233. doi: 10.1002/eji.1830050402. [DOI] [PubMed] [Google Scholar]
  30. Plata F., Jongeneel V., Cerottini J. C., Brunner K. T. Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells. Eur J Immunol. 1976 Nov;6(11):823–829. doi: 10.1002/eji.1830061114. [DOI] [PubMed] [Google Scholar]
  31. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  32. Sachs D. H., Cone J. L. Ir-associated murine alloantigens: demonstration of multiple Ia specificities in H-2 alloantisera after selective absorptions. J Immunol. 1975 Jan;114(1 Pt 1):165–169. [PubMed] [Google Scholar]
  33. Schrader J. W., Edelman G. M. Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex. J Exp Med. 1977 Mar 1;145(3):523–539. doi: 10.1084/jem.145.3.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shih T. Y., Weeks M. O., Troxler D. H., Coffin J. M., Scolnick E. M. Mapping host range-specific oligonucleotides within genomes of the ecotropic and mink cell focus-inducing strains of Moloney murine leukemia virus. J Virol. 1978 Apr;26(1):71–83. doi: 10.1128/jvi.26.1.71-83.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Strand M., August J. T. Structural proteins of mammalian oncogenic RNA viruses: multiple antigenic determinants of the major internal protein and envelope glycoprotein. J Virol. 1974 Jan;13(1):171–180. doi: 10.1128/jvi.13.1.171-180.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sugamura K., Shimizu K., Bach F. H. Involvement of fusion activity of ultraviolet light-inactivated Sendai virus in formation of target antigens recognized by cytotoxic T cells. J Exp Med. 1978 Jul 1;148(1):276–287. doi: 10.1084/jem.148.1.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Taniyama T., Holden H. T. Requirement of histocompatible macrophages for the induction of a secondary cytotoxic response to syngeneic tumor cells in vitro. J Immunol. 1979 Jul;123(1):43–49. [PubMed] [Google Scholar]
  38. Troxler D. H., Lowy D., Howk R., Young H., Scolnick E. M. Friend strain of spleen focus-forming virus is a recombinant between ecotropic murine type C virus and the env gene region of xenotropic type C virus. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4671–4675. doi: 10.1073/pnas.74.10.4671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yoshikura H. Effect of 5-fluorouracil on ultraviolet inactivation of virus production by murine sarcoma-leukemia virus complex carrier cells. Virology. 1972 Apr;48(1):193–200. doi: 10.1016/0042-6822(72)90126-2. [DOI] [PubMed] [Google Scholar]

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