Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1972 May;69(5):1069–1072. doi: 10.1073/pnas.69.5.1069

Activation of Leukemia Viruses by Graft-Versus-Host and Mixed Lymphocyte Reactions In Vitro

M S Hirsch *, S M Phillips †, C Solnik ‡, P H Black *, R S Schwartz ‡, C B Carpenter †
PMCID: PMC426630  PMID: 4402535

Abstract

Spleen cells from BALB/c or CAF1 mice released little or no detectable leukemia virus when cultured 2-7 days in vitro. In contrast, spleen cells of CAF1 mice previously inoculated with parental BALB/c spleen cells released leukemia viruses in 10 of 11 cases studied. Cultures of a mixture of spleen cells from normal BALB/c and CAF1 mice also contained leukemia viruses. Phytohemagglutinin induced the transformation of lymphocytes in cultures of CAF1 or BALB/c spleen cells, but this transformation did not activate leukemia viruses. It is concluded that mixed lymphocyte cultures in vitro, just as graft-versus-host reactions in vivo, can activate leukemia viruses that are normally present in a repressed form. This activation is not solely a function of lymphocyte transformation. The activated mouse leukemia virus may subsequently account for the observed high incidence of neoplasia in graft-versus-host disease.

Keywords: mice, mitomycin C, phytohemagglutinin

Full text

PDF
1069

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaronson S. A., Hartley J. W., Todaro G. J. Mouse leukemia virus: "spontaneous" release by mouse embryo cells after long-term in vitro cultivation. Proc Natl Acad Sci U S A. 1969 Sep;64(1):87–94. doi: 10.1073/pnas.64.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aaronson S. A., Todaro G. J., Scolnick E. M. Induction of murine C-type viruses from clonal lines of virus-free BALB-3T3 cells. Science. 1971 Oct 8;174(4005):157–159. doi: 10.1126/science.174.4005.157. [DOI] [PubMed] [Google Scholar]
  3. Adler W. H., Takiguchi T., Marsh B., Smith R. T. Cellular recognition by mouse lymphocytes in vitro. II. Specific stimulation by histocompatibility antigens in mixed cell culture. J Immunol. 1970 Oct;105(4):984–1000. [PubMed] [Google Scholar]
  4. Armstrong M. Y., Gleichmann E., Gleichmann H., Beldotti L., Andre-Schwartz J., Schwartz R. S. Chronic allogeneic disease. II. Development of lymphomas. J Exp Med. 1970 Sep 1;132(3):417–439. doi: 10.1084/jem.132.3.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fialkow P. J., Thomas E. D., Bryant J. I., Neiman P. E. Leukaemic transformation of engrafted human marrow cells in vivo. Lancet. 1971 Feb 6;1(7693):251–255. doi: 10.1016/s0140-6736(71)90998-6. [DOI] [PubMed] [Google Scholar]
  8. Granger G. A., Kolb W. P. Lymphocyte in vitro cytotoxicity: mechanisms of immune and non-immune small lymphocyte mediated target L cell destruction. J Immunol. 1968 Jul;101(1):111–120. [PubMed] [Google Scholar]
  9. Gross L., Feldman D. G. Electron microscopic studies of radiation-induced leukemia in mice: virus release following total-body x-ray irradiation. Cancer Res. 1968 Sep;28(9):1677–1685. [PubMed] [Google Scholar]
  10. Haran-Ghera N. Leukemogenic activity of centrifugates from irradiated mouse thymus and bone marrow. Int J Cancer. 1966 Jan;1(1):81–87. doi: 10.1002/ijc.2910010111. [DOI] [PubMed] [Google Scholar]
  11. Hartley J. W., Rowe W. P., Capps W. I., Huebner R. J. Isolation of naturally occurring viruses of the murine leukemia virus group in tissue culture. J Virol. 1969 Feb;3(2):126–132. doi: 10.1128/jvi.3.2.126-132.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hirsch M. S., Black P. H., Proffitt M. R. Immunosuppression and oncogenic virus infections. Fed Proc. 1971 Nov-Dec;30(6):1852–1857. [PubMed] [Google Scholar]
  13. Hirsch M. S., Black P. H., Tracy G. S., Leibowitz S., Schwartz R. S. Leukemia virus activation in chronic allogeneic disease. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1914–1917. doi: 10.1073/pnas.67.4.1914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huebner R. J., Kelloff G. J., Sarma P. S., Lane W. T., Turner H. C., Gilden R. V., Oroszlan S., Meier H., Myers D. D., Peters R. L. Group-specific antigen expression during embryogenesis of the genome of the C-type RNA tumor virus: implications for ontogenesis and oncogenesis. Proc Natl Acad Sci U S A. 1970 Sep;67(1):366–376. doi: 10.1073/pnas.67.1.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Igel H. J., Huebner R. J., Turner H. C., Kotin P., Falk H. L. Mouse leukemia virus activation by chemical carcinogens. Science. 1969 Dec 26;166(3913):1624–1626. doi: 10.1126/science.166.3913.1624. [DOI] [PubMed] [Google Scholar]
  16. Kaplan H. S. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed] [Google Scholar]
  17. Kasakura S., Lowenstein L. A factor stimulating DNA synthesis derived from the medium of leukocyte cultures. Nature. 1965 Nov 20;208(5012):794–795. doi: 10.1038/208794a0. [DOI] [PubMed] [Google Scholar]
  18. Klement V., Rowe W. P., Hartley J. W., Pugh W. E. Mixed culture cytopathogenicity: a new test for growth of murine leukemia viruses in tissue culture. Proc Natl Acad Sci U S A. 1969 Jul;63(3):753–758. doi: 10.1073/pnas.63.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lewis R. M., Armstrong M. Y., André-Schwartz J., Muftuoglu A., Beldotti L., Schwartz R. S. Chronic allogeneic disease. I. Development of glomerulonephritis. J Exp Med. 1968 Oct 1;128(4):653–679. doi: 10.1084/jem.128.4.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lowy D. R., Rowe W. P., Teich N., Hartley J. W. Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine. Science. 1971 Oct 8;174(4005):155–156. doi: 10.1126/science.174.4005.155. [DOI] [PubMed] [Google Scholar]
  21. Phillips S. M., Martin W. J., Shaw A. R., Wegmann T. G. Serum-mediated immunological non-reactivity between histoincompatible cells in tetraparental mice. Nature. 1971 Nov 19;234(5325):146–148. doi: 10.1038/234146a0. [DOI] [PubMed] [Google Scholar]
  22. Rowe W. P., Hartley J. W., Lander M. R., Pugh W. E., Teich N. Noninfectious AKR mouse embryo cell lines in which each cell has the capacity to be activated to produce infectious murine leukemia virus. Virology. 1971 Dec;46(3):866–876. doi: 10.1016/0042-6822(71)90087-0. [DOI] [PubMed] [Google Scholar]
  23. Sjögren's syndrome--newer aspects of research, diagnosis, and therapy. Ann Intern Med. 1971 Dec;75(6):937–950. [PubMed] [Google Scholar]
  24. Wilson D. B., Blyth JL NOWELL P. C. Quantitative studies on the mixed lymphocyte interaction in rats. 3. Kinetics of the response. J Exp Med. 1968 Nov 1;128(5):1157–1181. doi: 10.1084/jem.128.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ziff M. Viruses and the connective tissue diseases. Ann Intern Med. 1971 Dec;75(6):951–958. doi: 10.7326/0003-4819-75-6-951. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES