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. 1985 Apr 1;161(4):766–784. doi: 10.1084/jem.161.4.766

Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice

PMCID: PMC2189053  PMID: 2984305

Abstract

We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus- inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated for all isotypes except IgA. The viral infection leads to a rapid decline in T lymphocyte responses to mitogens and alloantigens, as well as a decrease in helper cell activity. Specific antibody responses to both T-dependent and T-independent antigens are impaired, and the response of B lymphocytes to mitogens is abolished. The profound immunosuppression seems to be due to the MuLV-induced polyclonal activation of lymphocytes. No active suppression of normal lymphocyte responses by cells from virus-infected mice was observed. The disease induced by the LP-BM5 MuLV isolate thus seems a promising model for the study of lymphocyte activation and the mechanisms of retrovirus-induced immunosuppression.

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Selected References

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  1. Copelan E. A., Rinehart J. J., Lewis M., Mathes L., Olsen R., Sagone A. The mechanism of retrovirus suppression of human T cell proliferation in vitro. J Immunol. 1983 Oct;131(4):2017–2020. [PubMed] [Google Scholar]
  2. DUNN T. B. Normal and pathologic anatomy of the reticular tissue in laboratory mice, with a classification and discussion of neoplasms. J Natl Cancer Inst. 1954 Jun;14(6):1281–1433. [PubMed] [Google Scholar]
  3. Davidson W. F., Chused T. M., Morse H. C., 3rd Genetic and functional analyses of the primary in vitro CTL: response of NZB lymphocytes to H-2-compatible cells. Immunogenetics. 1981 Mar 1;12(5-6):445–463. doi: 10.1007/BF01561687. [DOI] [PubMed] [Google Scholar]
  4. Davidson W. F., Fredrickson T. N., Rudikoff E. K., Coffman R. L., Hartley J. W., Morse H. C., 3rd A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol. 1984 Aug;133(2):744–753. [PubMed] [Google Scholar]
  5. Dent P. B. Immunodepression by oncogenic viruses. Prog Med Virol. 1972;14:1–35. [PubMed] [Google Scholar]
  6. Fowler A. K., Twardzik D. R., Reed C. D., Weislow O. S., Hellman A. Inhibition of lymphocyte transformation by disrupted murine oncornavirus. Cancer Res. 1977 Dec;37(12):4529–4531. [PubMed] [Google Scholar]
  7. Friedman H., Specter S., Bendinelli M. Influence of viruses on cells of the immune response system. Adv Exp Med Biol. 1983;162:463–474. doi: 10.1007/978-1-4684-4481-0_42. [DOI] [PubMed] [Google Scholar]
  8. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  9. Haas M., Meshorer A. Reticulum cell neoplasms induced in C57BL/6 mice by cultured virus grown in stromal hematopoietic cell lines. J Natl Cancer Inst. 1979 Aug;63(2):427–439. [PubMed] [Google Scholar]
  10. Haas M., Reshef T. Non-thymic malignant lymphomas induced in C57BL/6 mice by cloned dualtropic viruses isolated from hematopoietic stromal cell lines. Eur J Cancer. 1980 Jul;16(7):909–917. doi: 10.1016/0014-2964(80)90329-1. [DOI] [PubMed] [Google Scholar]
  11. Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayakawa K., Hardy R. R., Parks D. R., Herzenberg L. A. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J Exp Med. 1983 Jan 1;157(1):202–218. doi: 10.1084/jem.157.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hebebrand L. C., Mathes L. E., Olsen R. G. Inhibition of concanavalin A stimulation of feline lymphocytes by inactivated feline leukemia virus. Cancer Res. 1977 Dec;37(12):4532–4533. [PubMed] [Google Scholar]
  14. LATARJET R., DUPLAN J. F. Experiment and discussion on leukaemogenesis by cell-free extracts of radiation-induced leukaemia in mice. Int J Radiat Biol Relat Stud Phys Chem Med. 1962 Aug;5:339–344. doi: 10.1080/09553006214550911. [DOI] [PubMed] [Google Scholar]
  15. LIEBERMAN M., KAPLAN H. S. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. doi: 10.1126/science.130.3372.387. [DOI] [PubMed] [Google Scholar]
  16. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  17. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  18. Mathes L. E., Olsen R. G., Hebebrand L. C., Hoover E. A., Schaller J. P. Abrogation of lymphocyte blastogenesis by a feline leukaemia virus protein. Nature. 1978 Aug 17;274(5672):687–689. doi: 10.1038/274687a0. [DOI] [PubMed] [Google Scholar]
  19. Metroka C. E., Cunningham-Rundles S., Pollack M. S., Sonnabend J. A., Davis J. M., Gordon B., Fernandez R. D., Mouradian J. Generalized lymphadenopathy in homosexual men. Ann Intern Med. 1983 Nov;99(5):585–591. doi: 10.7326/0003-4819-99-5-585. [DOI] [PubMed] [Google Scholar]
  20. Mosier D. E., Mond J. J., Goldings E. A. The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect. J Immunol. 1977 Dec;119(6):1874–1878. [PubMed] [Google Scholar]
  21. Mosier D. E. Primary in vitro antibody responses by purified murine B lymphocytes in serum-free defined medium. J Immunol. 1981 Oct;127(4):1490–1493. [PubMed] [Google Scholar]
  22. Pattengale P. K., Taylor C. R., Twomey P., Hill S., Jonasson J., Beardsley T., Haas M. Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV). Am J Pathol. 1982 Jun;107(3):362–377. [PMC free article] [PubMed] [Google Scholar]
  23. Purtilo D. T., DeFlorio D., Jr, Hutt L. M., Bhawan J., Yang J. P., Otto R., Edwards W. Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. N Engl J Med. 1977 Nov 17;297(20):1077–1080. doi: 10.1056/NEJM197711172972001. [DOI] [PubMed] [Google Scholar]
  24. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  25. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  26. Sternberger L. A. The unlabeled antibody (PAP) method, introduction. J Histochem Cytochem. 1979 Dec;27(12):1657–1657. doi: 10.1177/27.12.392001. [DOI] [PubMed] [Google Scholar]
  27. Subbarao B., Mosier D. E. Activation of B lymphocytes by monovalent anti-Lyb-2 antibodies. J Exp Med. 1984 Jun 1;159(6):1796–1801. doi: 10.1084/jem.159.6.1796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ulmer A. J., Flad H. D. Discontinuous density gradient separation of human mononuclear leucocytes using Percoll as gradient medium. J Immunol Methods. 1979;30(1):1–10. doi: 10.1016/0022-1759(79)90268-0. [DOI] [PubMed] [Google Scholar]

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