Skip to main content
Log in

Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus

  • Original articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Mice infected i.v. with high doses of lymphocytic choriomeningitis virus (LCMV; 105–106 plaqueforming units) 8–10 days prior to challenge with the methylcholanthrene-induced fibrosarcoma tumor cell line MC57G or the melanoma cell line B16 tumor cells showed an enhanced tumor susceptibility with respect to both growth kinetics of the tumor and the minimal dose necessary for tumor take. After transient initial growth, MC57G tumor cells were all rejected by uninfected C57BL/6 mice by day 14. Mice preinfected i.v. with LCMV 3 weeks before or at the time of tumor challenge, but not those infected 2 months before or 7 days after, showed increasing tumor growth, the tumor take being 100% for 106, 50% for 105 and 37% for 104 MC57G tumor cells injected into the footpad compared with resistance to 106 cells in normal mice. B16 melanoma cells also grew more rapidly in LCMV-preinfected mice and by day 40 tumors were established with about 100 times fewer cells, i.e. about 103 compared with 3×104−3×105 for uninfected mice. Analysis of the growth of tumor cells in normal and in LCMV-carrier mice revealed that the latter mice were not more susceptible to LCMV-infected than to uninfected MC57G. Since LCMV-carrier mice fail to mount LCMV-specific T cell responses, these results suggest that anti-LCMV-specific T cells may be responsible for acquired immunodeficiency hampering immune surveillance against the tumors studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aden DP, Knowles BB (1976) Cell surface antigen coded for the human chromosome 7. Immunogenetics 3: 209

    Google Scholar 

  2. Ahmed R, King C, Oldstone MBA (1987) Virus-lymphocyte interaction: T cells of the helper subset are infected with lymphocytic choriomeningitis virus during persistent infection in vivo. J Virol 61: 1571

    Google Scholar 

  3. Bekesi JG, St-Arneault G, Holland JF (1972) Immunogenicity of leukemia L1210 cells after neuraminidase treatment. J Natl Cancer Inst 49: 107

    Google Scholar 

  4. Boog CJP, Boes J, Melief CJM (1988) Stimulation with dendritic cells decreases or obviates the CD4+ helper cell requirement in cytotoxic T lymphocyte responses. Eur J Immunol 18: 219

    Google Scholar 

  5. Boone CW, Blackman K (1972) Augmented immunogenicity of tumor cell homogenates infected with influenza virus. Cancer Res 32: 1018

    Google Scholar 

  6. Bro-Jörgensen K, Volkert M (1974) Defect in the immune system of mice infected with lymphocytic choriomeningitis virus. Infect Immun 9: 605

    Google Scholar 

  7. Buchmeier MJ, Welsh RM, Dutko FJ, Oldstone MBA (1980) The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol 30: 275

    Google Scholar 

  8. Centers of Disease Control Task Force (1982) Epidemiological aspects of the current outbreak of Kaposi's sarcoma and opportunistic infections. N Engl J Med 306: 248

    Google Scholar 

  9. Cobbold SP, Jayasuriya A, Nash A, Prospero TD, Waldmann H (1984) Therapy with monoclonal antibodies by elimination of T cell subsets in vivo. Nature 312: 548

    Google Scholar 

  10. Cole GA, Nathanson N, Prendergast RA (1972) Requirement for thetabearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature 238: 335

    Google Scholar 

  11. Doherty PC, Zinkernagel RM (1974) T cell-mediated immunopathology in viral infection. Transplant Rev 19: 89

    Google Scholar 

  12. Fauci AS (1988) The human immunodeficiency virus: Infectivity and mechanisms of pathogenesis. Science 239: 617

    Google Scholar 

  13. Fernandez-Cruz E, Woda BA, Feldman JD (1980) Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes J Exp Med 152: 823

    Google Scholar 

  14. Fidler IJ (1973) Selection of successive tumor lines for metastasis. Nature 242: 148

    Google Scholar 

  15. Fidler IJ, Nicolson GL (1976) Brief communication: organ selectivity for implantation survival and growth of B16 melanoma variant tumor lines. J Natl Cancer Inst 57: 1199

    Google Scholar 

  16. Fujiwara H, Moriyama Y, Suda T, Tsuchida T, Shearer GM, Hamaoka T (1984) Enhanced TNP-reactive helper T cell activity and its utilization in the induction of amplified tumor immunity that results in tumor regression. J Immunol 132: 1571

    Google Scholar 

  17. Fujiwara H, Yoshioka T, Shima J, Kosugi A, Itoh K, Hamaoka T (1986) Helper T cells against tumor-associated antigens (TAA): preferential induction of helper T cell activities involved in anti-TAA cytotoxic T lymphocyte and antibody responses. J Immunol 136: 2715

    Google Scholar 

  18. Gold K, Thomas D, Garret TJ (1982) Aggressive Kaposi's sarcoma in a heterosexual drug addict (New York City). N Engl J Med 307: 498

    Google Scholar 

  19. Hamburg V, Svet-Moldavsky G (1967) Suppression of viral and chemical carcinogenesis by means of artificial heterogenization. Nature 215: 230

    Google Scholar 

  20. Hotchin J (1971) Persistent and slow virus infections. Monogr Virol 3: 1

    Google Scholar 

  21. Jacobson S, Friedman RM, Pfau CJ (1981) Interferon induction by lymphocytic choriomeningitis viruses correlates with maximum virulence. J Gen Virol 57: 275

    Google Scholar 

  22. Lehmann-Grube F (1971) Lymphocytic choriomeningitis virus. Virol Monogr 10: 1

    Google Scholar 

  23. Lehmann-Grube F (1984) Bacterial and viral inhibition and modulation of host defences. Academic Press, London, pp 211–242

    Google Scholar 

  24. Lehmann-Grube F, Ambrassat J (1977) A new method to detect lymphocytic choriomeningitis virus-specific antibody in human sera. J Gen Virol 37: 85

    Google Scholar 

  25. Lehmann-Grube F, Assmann-Wischer U, Löliger C, Moskophidis D, Löhler J (1985) Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in clearance of lymphocytic choriomeningitis virus from spleens of mice. J Immunol 134: 608

    Google Scholar 

  26. Leist TP, Cobbold SP, Waldmann H, Aguet M, Zinkernagel RM (1987) Functional analysis of T lymphocyte subsets in antiviral host defense, J Immunol 138: 2278

    Google Scholar 

  27. Leist TP, Eppler M, Rüedi E, Zinkernagel RM (1988) Virus triggered AIDS in mice is a T cell mediated immunopathology caused by virus-specific cytotoxic T cells: prevention by tolerance or by treatment with anti-CD8 antibodies. J Exp Med 167: 1749

    Google Scholar 

  28. Leist TP, Eppler M, Zinkemagel RM (1989) Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-IFN gamma-treated mice. J Virol 63: 2813

    Google Scholar 

  29. Levy JA, Ziegler JL (1983) Acquired immune deficiency syndrome (AIDS) is an opportunistic infection and Kaposi's sarcoma results from secondary immune stimulation. Lancet 2: 78

    Google Scholar 

  30. Lindenmann J, Klein PA (1967) Viral oncolysis: increased immunogenicity of host cell antigen associated with influenza virus. J Exp Med 126: 93

    Google Scholar 

  31. Löhler J, Lehmann-Grube F (1981) Immunopathologic alterations of lymphatic tissues of mice infected with lymphocytic choriomeningitis virus. I Histopathologic findings. Lab Invest 44: 193

    Google Scholar 

  32. Mims CA (1966) Immunofluorescene study of the carrier state and mechanism of vertical transmission in lymphocytic choriomeningitis virus infection in mice. Pathol Bacteriol 91: 395

    Google Scholar 

  33. Mims CA, Subrahmanyan TP (1966) Immunofluorescence study of the mechanism of resistance to superinfection in mice carrying the lymphocytic choriomeningitis virus. J Pathol Bacteriol 91: 403

    Google Scholar 

  34. Mims CA, Wainwright S (1968) The immunodepressive action of lymphocytic choriomeningitis virus in mice. J Immunol 101: 717

    Google Scholar 

  35. Minato N, Bloom BR, Jones Ch, Holland J, Reid LM (1979) Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice. J Exp Med 119: 1117

    Google Scholar 

  36. Molomut N, Padnos M, Gross L, Satory V (1964) Inhibition of a transplantable murine leukaemia by a lymphocytopenic virus. Nature 204: 1003

    Google Scholar 

  37. Moore A (1960) The oncolytic viruses. Prog Exp Tumor Res 1: 411

    Google Scholar 

  38. Oldstone MBA, Tishon A, Chiller JM, Weigle WO, Dixon FJ (1973) Effect of chronic viral infection on the immune system: I. comparison of the immune responsiveness of mice chronically infected with LCM virus with that of noninfected mice. J Immunol 110: 1268

    Google Scholar 

  39. Popescu M, Löhler J, Lehmann-Grube F (1979) Infectious lymphocytes in lymphocytic choriomeningitis virus carrier mice. J Gen Virol 42: 481

    Google Scholar 

  40. Quinn TC, Mann JM, Curran JW, Piot P (1986) AIDS in africa: an epidemiologic paradigm. Science 234: 955

    Google Scholar 

  41. Rogers MF, Morens DM, Stewart JA et al. (1983) National casecontrol study of Kaposi's sarcoma and pneumocystis carinii pneumonia in homosexual men: II. Laboratory results. Ann Intern Med 99: 151

    Google Scholar 

  42. Roost HP, Charan S, Gobet R, Rüedi E, Hengartner H, Althage A, Zinkernagel RM (1988) An acquired immunodeficiency in mice caused by infection with lymphocytic choriomeningitis virus. Eur J Immunol 18: 511

    Google Scholar 

  43. Schroff R, Gottlieb MS, Prince HE et al. (1983) Immunological studies of homosexual men with immunodeficiency and Kaposi's sarcoma. Clin Immunol Immunopathol 27: 300

    Google Scholar 

  44. Shearer GM (1986) AIDS: an autoimmune pathologic model for the destruction of a subset of helper T lymphocytes. Mount Sinai 53: 609

    Google Scholar 

  45. Takai Y, Kosugi A, Yoshioka T, Tomita S, Fujiwara H, Hamaoka T (1985) T-T cell interaction in the induction of delayed-type hypersensitivity (DTH) respones: vaccinia virus-reactive helper T cell activity involved in enhanced in vivo induction of DTH responses and its application to augmentation of tumor-specific DTH responses. J Immunol 134: 108

    Google Scholar 

  46. Traub E (1936) Persistence of lymphocytic choriomeningitis virus in immune animals and its relation to immunity. J Exp Med 63: 847

    Google Scholar 

  47. Traub E (1962) Can LCMV virus cause lymphomatosis in mice? Arch Gesamte Virusforsch 11: 667

    Google Scholar 

  48. Van Pel A, Boon Th (1982) Protection against a nonimmunogenic mouse leukemia by an immunogenic variant obtained by mutagenesis. Proc Natl Acad Sci USA 79: 4718

    Google Scholar 

  49. Walker CM, Moody DJ, Stites DP, Levy JA (1986) CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234: 1563

    Google Scholar 

  50. Welsh RM, Zinkernagel RM (1977) Heterospecific cytotoxic cells during acute lymphocytic choriomeningitis virus infection. Nature 268: 646

    Google Scholar 

  51. Wheelock EF, Toy ST (1973) Participation of lymphocytes in viral infections. Adv Immunol 16: 123

    Google Scholar 

  52. Wise KS (1977) Vesicular stomatitis virus-infected L1210 murine leukemia cells: increased immunogenicity and altered surface antigens. J Natl Cancer Inst 58: 83

    Google Scholar 

  53. Youn JK, Barski G (1966) Interference between lymphocytic choriomeningitis and rauscher leukemia in mice. J Natl Cancer Inst 37: 381

    Google Scholar 

  54. Yu AS, Bernstein ID (1982) T helper cells in immune mice amplify the primary anti-tumor cytotoxic response. J Immunol 129: 856

    Google Scholar 

  55. Zeigler JL, Stites DP (1986) Hypothesis: AIDS is an autoimmune disease directed at the immune system and triggered by a lymphotropic retrovirus. Clin Immunol Immunopathol 41: 305

    Google Scholar 

  56. Zinkernagel RM (1988) Virus triggered AIDS is a T cell mediated immunopathology: prevention by tolerance or by treatment with anti-CD8 antibodies. Immunol Today 9: 370

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by grants from the Swiss National Science Foundation 3.259–0.87 and the Kanton of Zürich

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kohler, M., Rüttner, B., Cooper, S. et al. Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus. Cancer Immunol Immunother 32, 117–124 (1990). https://doi.org/10.1007/BF01754208

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01754208

Keywords

Navigation