Loss of Tumorigenicity Following in Vitro MuLV Infection is Associated with Induction of Peritoneal Natural Killer Cell Activity

  • Karin Thiel
  • Eugene V. Genovesi
  • J. Dirk Iglehart
  • Dani P. Bolognesi
  • Kent J. Weinhold
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 239)


Infection by an attenuated replication-competent murine retrovirus (Friend leukemia virus-FLV4) ,but not other non-transforming retroviruses, stimulated rejection of transplantable thymomas (RL-cell line) and subsequent tumor immunity in syngeneic mouse recipients. FLV-infected RL-cells (RL-FLV) were unaltered in their in vitro growth, and grew progressively to kill sublethally irradiated animals and nude mice. Primary RL-FLV rejection was due to induction of increased natural killer (NK)-cell activity limited to peritoneal sites of tumor inoculation with a minor cytolytic macrophage population. Syngeneic mutant beige (NK-deficient) mice similarly rejected RL-FLV cells with increased peritoneal NK-cell activity and acquired immunity to the parental RL-tumor. While RL-FLV stimulated far greater peritoneal NK activity than did other tested retrovirus-infected RL-cells, the inherent susceptibility of these cells to lysis by normal NK cells was not altered by virus. RL-FLV induced NK effectors showed an indiscriminant lysis pattern that was independent of target cell type and retrovirus expression. Reconstitution studies revealed a necessary T-lymphocyte component for NK-cell stimulation by RL-FLV in mice, which may be lymphokine-mediated, but not


Natural Killer Cell Natural Killer Activity Peritoneal Cell Beige Mouse Splenic Natural Killer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gorczynski, R.M. (1974). Evidence for in vivo protection against murine sarcoma virus induced tumors by T lynphocytes from immune animals. J Immunol. 112: 533.PubMedGoogle Scholar
  2. 2.
    Shellam, G.R., R.A. Knight, N.A. Mitchinson, R.N. Gorczynski and A. Maoz. 1976. The specificity of effector T cells activated by tumours induced by murine oncornaviruses. Transplant Rev. 29: 249.PubMedGoogle Scholar
  3. 3.
    Gomard, E., J. Wybier-Franqui, and J.P. Levy. 1981. Accessory cells in the in vitro generation of type C virus specific T killer lymphocytes I Role of macrophages in primary anti-FMR reaction. J Immunol. 126: 891.PubMedGoogle Scholar
  4. 4.
    Al-Ghazzouli, I.K., R.M. Donahue, K. Huang, B. Sass, R.L. Peters and G.J. Kelloff. 1976. Immunity to virus-free syngeneic tumor cell transplantation in the BALB/c mouse after immunization with homologous tumor cells infected with type C virus. J Immunol. 117: 2239.PubMedGoogle Scholar
  5. 5.
    Boone, C.W., N. Takeichi, F.C. Austin, E. Gotohda, T. Oikawa and R. Gillette. 1979. Virus augmentation: increased immunogenicity of tumor-associated transplantation antigens in tumor cell extracts after infection with surface budding viruses. In: GANN Monograph on Cancer Research, 1123, p. 7.Google Scholar
  6. 6.
    Liberman, M., A. DeCleve, P. Ricciardi-Castagnoli, J. Boniver, O.J. Finn, and H.S. Kaplan. 1979. Establishment, characterization, and virus expression of cell lines derived from radiation-and virus-induced lymphomas of C57B1/Ka mice. Int J Cancer 24: 168.CrossRefGoogle Scholar
  7. 7.
    Seifert, E., M. Claviez, H. Frank, G. Hunsmann, H. Schwarz, and W. Schafer. 1975. Properties of mouse leukemia viruses. XII. Production of substantial amounts of Friend Leukemia virus by a suspension tissue culture line Eveline suspension cells. Z Naturforsch 30: 698.Google Scholar
  8. 8.
    Bassin, R.H., N. Tuttle, and P.J. Fischinger. 1971. Rapid cell culture assay technique for murine leukemia viruses. Nature 229: 564.PubMedCrossRefGoogle Scholar
  9. 9.
    Green, R.W., D.P. Bolognesi, and W. Schafer. 1973. Polypeptides of mammalian oncornaviruses I Isolation and serological analysis of polypeptides from murine and feline C-type viruses. Virology 56: 565.PubMedCrossRefGoogle Scholar
  10. 10.
    Schon-Hegard, M.A. and P.G. Holt. 1981. Improved method for the isolation of purified mouse peritoneal macrophages. J Immunol Methods 43: 169.CrossRefGoogle Scholar
  11. 11.
    Julius, M.H., E. Simpson, and L.A. Herzenberg. 1973. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 3: 645.PubMedCrossRefGoogle Scholar
  12. 12.
    Bolognesi, D.P., J.J. Collins, J.P. Leis, V. Moennig, W. Schafer and P.H. Atkinson. 1975. Role of carbohydrate in determining the immunochemical properties of the major glycoprotein (gp71) of Friend murine leukemia virus. J Virol. 16: 1453.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Rom, R.M., J.C. Palmer, and L.A. Manson. 1974. A simplified Cr-release assay for killer cells. J Immunol. Methods 3: 301.Google Scholar
  14. 14.
    Fischinger, P.J., H.-J. Thiel, M. Lieberman, H.S. Kaplan, N.M. Dunlop, and W.G. Robey. 1982. Presence of a novel recombinant murine leukemia virus-like glycoprotein on the surface of virusnegative C57BL lymphoma cells. Cancer Res. 42: 4650.PubMedGoogle Scholar
  15. 15.
    Weinhold, K.J., L.T. Goldstein, and E.F. Wheelock. 1979. The tumor dormant state: Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice. J Exp Med. 149: 732.PubMedCrossRefGoogle Scholar
  16. 16.
    Corer, P.A. and D.B. Amos. 1956. Passive immunity in mice against C57BL leukosis EL4 by means of iso-immune serum. Cancer Res. 16: 338.Google Scholar
  17. 17.
    Patuleia, M.C. and C. Friend. 1967. Tissue culture studies on murine virus-induced leukemia cells: Isolation of single cells in agar-liquid medium. Cancer Res. 27: 726.Google Scholar
  18. 18.
    Law, L.W., T.B. Dunn, P.J. Boyle, and J.H. Miller. 1949. Observations on the effects of a folic-acid antagonist on transplantable lymphoid leukemias in mice. J Natl Cancer Inst. 10: 179.PubMedGoogle Scholar
  19. 19.
    McCoy, J.L., A. Fefer, and J.P. Glynn. 1967. Comparative studies on the induction of transplantation resistance in BALB/c and C57BL/6 mice in three murine leukemia systems. Cancer Res. 27: 1743.PubMedGoogle Scholar
  20. 20.
    Klein, E., and G. Klein. 1964. Antigenic properties of lymphoma induced by the Moloney agent. J Natl Cancer Inst. 32: 547.PubMedGoogle Scholar
  21. 21.
    Iglehart, J.D., E.C. Ward, K. Thiel, G. Huper, S.S. Geier, and D.P. Bolognesi. 1981. In vivo antigenic modification of tumor cell I Introduction of murine leukemia virus antigens on non-virusproducing murine sarcomas. J Natl Cancer Inst. 67: 107.PubMedGoogle Scholar
  22. 22.
    Henderson, I.C., M.M. Lieber, and G.J. Todaro. 1974. Mink cell line MulLu (CCL 64). Focus formation and the generation of ‘nonproducer’ transformed cell lines with murine and feline sarcoma viruses. Virology 60: 282.Google Scholar
  23. 23.
    Roder, J.C. 1979. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J Immunol. 123: 2168.Google Scholar
  24. 24.
    Roder, J.C., M.-L. Lohmann-Mathes, W. Domzig, and H. Wigzell. 1979. The beige mutation in the mouse II Selectivity of the natural killer ( NK) cell defect. J Immunol. 123: 2174.Google Scholar
  25. 25.
    Hammerling, G.J., Un Hammerling, and L. Flaherty. 1979. Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies. J Exp Med. 150: 108.PubMedCrossRefGoogle Scholar
  26. 26.
    Welsh, R.M. 1981. Natural cell-mediated immunity during viral infections. Curr Top Microbiol Immunol. 92: 83.PubMedGoogle Scholar
  27. 27.
    Welsh, R.M. 1978. Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. I. Characterization of natural killer cell induction. J Exp Med. 148: 163.Google Scholar
  28. 28.
    Casali, P., J.G.P. Simmons, M.J. Buchmeier, and M.A. Oldstone, 1981. In vitro generation of human cytotoxic lymphocytes by virus Viral glycoproteins induce nonspecific cell-mediated cytotoxicity without release of interferon. J Exp Med. 154: 840.PubMedCrossRefGoogle Scholar
  29. 29.
    Iglehart, J.D., E.C. Ward, G. Huper, K. Thiel, and D.P. Bolognesi. 1981. In vivo antigenic modification of tumor cells II Distribution of virus in sarcoma-bearing mice. J Natl Cancer Inst. 67: 117.PubMedGoogle Scholar
  30. 30.
    Rager-Zisman, B., and B.R. Bloom. 1982. Natural killer cells in resistance to virus-infected cells. In: Springer Semin. Immunopathol. 4:397, Springer-Verlag.Google Scholar
  31. 31.
    Lane, M.A. 1980. Murine retrovirus-specific natural killer cell activity. In: Natural cell-mediated immunity against tumors. Edited by R.B. Herberman. Academic Press, New York. Pp. 921–938.Google Scholar
  32. 32.
    Welsh, R.M., R.M. Zinkernagel and L.A. Hallenbeck. 1979. Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice II ‘Specificities’ of the natural killer cells. J Immunol. 122: 475.PubMedGoogle Scholar
  33. 33.
    Djeu, J.Y., J.A. Heinbaugh, J.T. Holden, and R.B. Herberman. 1979. Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol. 122: 175.PubMedGoogle Scholar
  34. 34.
    Welsh, R.M. and R.W. Kiessling. 1980. Natural killer cell response to lymphocytic choriomeningitis virus in beige mice. Scand J Immunol. 11: 363.PubMedCrossRefGoogle Scholar
  35. 35.
    Henney, C.S., K. Kuribayashi, D.E. Kern and S. Gillis. 1981. Interleukin-2 augments natural killer cell activity. Nature 291: 235.CrossRefGoogle Scholar
  36. 36.
    Kiessling, R., E. Eriksson, L.A. Hallenbeck, and R.M. Welsh. 1980. A comparative analysis of the cell surface properties of activated vs endogenous mouse natural killer cells. J Immunol. 125: 1551.PubMedGoogle Scholar
  37. 37.
    Minato, N., L. Reid, and B.R. Bloom. 1981. On the heterogeneity of murine natural killer cells. J. Exp. Med. 154: 750.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Karin Thiel
    • 1
  • Eugene V. Genovesi
    • 1
  • J. Dirk Iglehart
    • 1
  • Dani P. Bolognesi
    • 1
  • Kent J. Weinhold
    • 1
    • 2
  1. 1.Department of SurgeryDuke University Medical CenterDurhamUSA
  2. 2.Duke University Medical CenterDurhamUSA

Personalised recommendations