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Cytoimitiunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system

Abstract

The mechanism(s) by which infectious or malignant material is cleared by the host has long been an area of intensive study. We have used the murine model of infection with lymphocytic choriomeningitis virus (LCMV) to look at immune clearance during persistent infection. LCMV was selected because the mouse is its natural host, it easily induces acute or persistent infection in vivo, and the mechanism by which it is cleared in vivo during acute infection is now well understood1–8. Clearance, although associated with several antiviral immune effector mechanisms1, is primarily dependent on the activity of virus-specific cytotoxic T lymphocytes (CTL) restricted by H–2 molecules of the mouse major histocompatibility complex (MHC)4–8. If these cells fail to generate or are depleted, progression from acute to persistent infection occurs1,9,10. Here, using molecular probes, we show that viral nucleic acid sequences, viral proteins and infectious materials can be efficiently and effectively cleared by adoptive transfer of antiviral H–2-restricted lymphocytes bearing the Lyt 2+ phenotype. Viral materials are cleared from a wide variety of tissues and organs where they normally lodge during persistent infection. Unexpectedly, the mode by which viral materials are removed from the central nervous system (CNS) differed markedly from the mechanism of clearance occurring at other sites. These observations indicate the possible use of adoptive lymphocyte therapy for treatment of persistent infections and suggest that immune clearance of products from the CNS probably occurs by a process distinct from those in other organs.

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References

  1. Buchmeier, M. J., Welsh, R. M., Dutko, F. J. & Oldstone, M. B. A. Adv. Immun. 30, 275–331 (1980).

    Article  CAS  Google Scholar 

  2. Hotchin, J. Monogr. Virol. 3, 1–21 (1971).

    Article  Google Scholar 

  3. Lehmann-Grube, F. Monogr. Virol. 10, 28–54 (1971).

    Google Scholar 

  4. Cole, G. A., Nathanson, N. & Prendergast, R. A. Nature 238, 335–338 (1972).

    Article  ADS  CAS  Google Scholar 

  5. Doherty, P. C. & Zinkernagel, R. M. Transplantn Rev. 19, 81–94 (1974).

    Google Scholar 

  6. Lehmann-Grube, F. et al. J. Immun. 134, 608–614 (1985).

    CAS  PubMed  Google Scholar 

  7. Zinkernagel, R. M. & Welsh, R. M. J. Immun. 117, 1495–1502 (1976).

    CAS  PubMed  Google Scholar 

  8. Byrne, J. A. & Oldstone, M. B. A. J. Virol. 51, 682–686 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Rowe, W. R. Res. Rep. nav. Med. Res. Instn 12, 167–178 (1954).

    Google Scholar 

  10. Ahmed, R. et al. J. exp. Med. 60, 521–540 (1984).

    Article  Google Scholar 

  11. Southern, P. J., Blount, P. & Oldstone, M. B. A. Nature 312, 555–558 (1984).

    Article  ADS  CAS  Google Scholar 

  12. Buchmeier, M. J. & Oldstone, M. B. A. J. Immun. 120, 1297–1304 (1978).

    CAS  PubMed  Google Scholar 

  13. Thomsen, A., Volkert, M. & Marker, O. Immunology 55, 213–223 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Byrne, J. A. & Oldstone, M. B. A. J. Immun. 136, 698–704 (1986).

    CAS  PubMed  Google Scholar 

  15. Ahmed, R., Byrne, J. A. & Oldstone, M. B. A. J. Virol. 51, 34–41 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Byrne, J. A., Ahmed, R. & Oldstone, M. B. A. J. Immun. 133, 433–439 (1984).

    CAS  PubMed  Google Scholar 

  17. Zinkernagel, R. M. & Doherty, P. C. Adv. Immun. 27, 52–177 (1979).

    Google Scholar 

  18. Örn, A. et al. Nature 297, 415–417 (1982).

    Article  ADS  Google Scholar 

  19. Raulet, D. H., Gottlieb, P. D. & Bevan, M. J. J. Immun. 125, 1136–1143 (1980).

    CAS  PubMed  Google Scholar 

  20. Dialynas, D. P. et al. J. Immun. 131, 2445–2451 (1983).

    CAS  PubMed  Google Scholar 

  21. Cobbold, S. P. et al. Nature 312, 548–551 (1984).

    Article  ADS  CAS  Google Scholar 

  22. Blount, P. et al. Brain Res. (in the press).

  23. Oldstone, M. B. A. & Dixon, F. J. J. exp. Med. 129, 483–505 (1969).

    Article  CAS  Google Scholar 

  24. Notkins, A. L. & Oldstone, M. B. A. Concepts in Viral Pathogenesis Vol. 1 (Springer, New York, 1984).

    Book  Google Scholar 

  25. Dixon, F. J. & Fisher, D. W. The Biology of Immunologie Disease (Sinauer Associates, Massachusetts, 1983).

    Google Scholar 

  26. Zinkernagel, R. M. & Althage, A. J. exp. Med. 145, 644–651 (1977).

    Article  CAS  Google Scholar 

  27. Anderson, J. et al. J. Virol. 53, 552–560 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Rodriguez, M., Buchmeier, M. J., Oldstone, M. B. A. & Lampert, P. W. Am. J. Path. 110, 95–100 (1983).

    CAS  PubMed  Google Scholar 

  29. Vitetta, E. S. & Capra, J. D. Adv. Immun. 26, 147–193 (1978).

    Article  CAS  Google Scholar 

  30. Wong, G. H. W. et al. Nature 310, 688–691 (1984).

    Article  ADS  CAS  Google Scholar 

  31. Main, E. et al. J. Immun. 135, 242–246 (1985).

    CAS  PubMed  Google Scholar 

  32. Stewart, W. E. The Interferon System (Springer, New York, 1979).

    Book  Google Scholar 

  33. Langyel, P. A. Rev. Biochem. 51, 251–282 (1982).

    Article  Google Scholar 

  34. Maheshwari, R. K. & Friedman, R. Meth. Enzym. 79, 451–478 (1981).

    Article  CAS  Google Scholar 

  35. Southern, P. J. et al. in Vaccines 86: Modern Approaches to Vaccines (eds Lerner, R. A., Chanock, R. M. & Brown, F.) (Cold Spring Harbor Laboratory, New York, in the press).

  36. Bishop, D. H. L. & Compans, R. W. Curr. Topics Microbiol. Immun. 114, 153–175 (1985).

    Google Scholar 

  37. Volkert, M. Acta path. microbiol. scand. 57, 465–474 (1963).

    Article  CAS  Google Scholar 

  38. Casali, P., Rice, G. P. A. & Oldstone, M. B. A. J. exp. Med. 159, 1322–1337 (1984).

    Article  CAS  Google Scholar 

  39. Schrier, R. D., Nelson, J. A. & Oldstone, M. B. A. Science 230, 1048–1051 (1985).

    Article  ADS  CAS  Google Scholar 

  40. Hoxie, J. A. et al. Science 229, 1400–1402 (1985).

    Article  ADS  CAS  Google Scholar 

  41. Margolick, J., Volkman, D., Lane, H. & Fauci, A. J. clin. Invest. 76, 709–715 (1985).

    Article  CAS  Google Scholar 

  42. Pelton, B. K., Imrie, B. & Denman, A. Nature 259, 582–584 (1976).

    Article  Google Scholar 

  43. McChesney, M. B., Fujinami, R. S. & Oldstone, M. B. A. J. exp. med. (in the press).

  44. Schrier, R. D. & Oldstone, M. B. A. J. Virol. (in the press).

  45. Schrier, R. D., Rice, G. P. A. & Oldstone, M. B. A. J. infect. Dis. (in the press).

  46. Eng, L., Vanderhaeghen, J. J., Bijnami, A. & Gerstl, B. Brain Res. 28, 351–362 (1981).

    Article  Google Scholar 

  47. Oldstone, M. B. A., Tishon, A. & Buchmeier, M. J. J. Immun. 130, 912–918 (1983).

    CAS  PubMed  Google Scholar 

Download references

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Oldstone, M., Blount, P., Southern, P. et al. Cytoimitiunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature 321, 239–243 (1986). https://doi.org/10.1038/321239a0

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