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. 1985 Feb;53(2):489–494. doi: 10.1128/jvi.53.2.489-494.1985

Treatment of mice with polyinosinic-polycytidilic polyribonucleotide reduces T-cell involvement in a localized inflammatory response to vaccinia virus challenge.

R Korngold, P C Doherty
PMCID: PMC254661  PMID: 2578572

Abstract

Mice inoculated intracerebrally with 10(3) PFU of vaccinia virus developed a nonfatal meningitis which was maximal 7 days after challenge. Intravenous administration of an interferon (IFN) inducer, polyinosinic-polycytidilic polyribonucleotide [poly(I)-poly(C)], on days 4 and 6 postinjection was associated with a three- to fourfold decrease in the number of T lymphocytes present in cerebrospinal fluid, reflected primarily by a decreased number of vaccinia virus-specific cytotoxic T-lymphocyte precursors. The lack of a concomitant reduction in the overall cytotoxic activity of cerebrospinal fluid cells directed against virus-infected target cells seemed to be largely due to an increase in natural killer cell activity. IFN was implicated as mediating the effect of poly(I)-poly(C) because high systemic levels of IFN were evident after injection, and neither the magnitude of the inflammatory response nor the T-cell levels were affected when poly(I)-poly(C)-treated mice were also given anti-IFN antiserum. However, the poly(I)-poly(C)-induced IFN did not seem to reduce the localized inflammatory response by affecting viral replication in brain tissue because the vaccinia virus titers present on days 6 through 8 of infection were similar to the titers in phosphate-buffered saline controls. These findings are consistent with either an effect of IFN on T-cell recruitment to the central nervous system or an inhibition of proliferation of cells participating in the response. These findings suggest that there is a potential source of complications for clinical protocols that use IFN or inducers to enhance T-cell function in various disease situations, and this effect of IFN may be a contributing factor to the immunosuppression often associated with many viral infections.

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Selected References

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  1. Bennink J. R., Doherty P. C. T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells. J Exp Med. 1978 Jul 1;148(1):128–135. doi: 10.1084/jem.148.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bruce J., Symington F. W., McKearn T. J., Sprent J. A monoclonal antibody discriminating between subsets of T and B cells. J Immunol. 1981 Dec;127(6):2496–2501. [PubMed] [Google Scholar]
  3. Cerottini J. C., Brunner K. T., Lindahl P., Gresser I. Inhibitory effect of interferon preparations and inducers on the multiplication of transplanted allogeneic spleen cells and syngeneic bone marrow cells. Nat New Biol. 1973 Apr 4;242(118):152–153. doi: 10.1038/newbio242152a0. [DOI] [PubMed] [Google Scholar]
  4. DENT P. B., PETERSON R. D., GOOD R. A. A DEFECT IN CELLULAR IMMUNITY DURING THE INCUBATION PERIOD OF PASSAGE A LEUKEMIA IN C3H MICE. Proc Soc Exp Biol Med. 1965 Jul;119:869–871. doi: 10.3181/00379727-119-30323. [DOI] [PubMed] [Google Scholar]
  5. De Maeyer-Guignard J., Cachard A., De Maeyer E. Delayed-type hypersensitivity to sheep red blood cells: inhibition of sensitization by interferon. Science. 1975 Nov 7;190(4214):574–576. doi: 10.1126/science.1188355. [DOI] [PubMed] [Google Scholar]
  6. De Maeyer E., De Maeyer-Guignard J. Effect of interferon on cell-mediated immunity. Tex Rep Biol Med. 1977;35:370–374. [PubMed] [Google Scholar]
  7. De Maeyer E., De Maeyer-Guignard J., Vandeputte M. Inhibition by interferon of delayed-type hypersensitivity in the mouse. Proc Natl Acad Sci U S A. 1975 May;72(5):1753–1757. doi: 10.1073/pnas.72.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doherty P. C., Korngold R. Characteristics of poxvirus-induced meningitis: virus-specific and non-specific cytotoxic effectors in the inflammatory exudate. Scand J Immunol. 1983 Jul;18(1):1–7. doi: 10.1111/j.1365-3083.1983.tb00828.x. [DOI] [PubMed] [Google Scholar]
  9. Doherty P. C., Korngold R. Hierarchies of T cell responsiveness are reflected in the distribution of effector T cells in viral meningitis. Aust J Exp Biol Med Sci. 1983 Aug;61(Pt 4):471–475. doi: 10.1038/icb.1983.44. [DOI] [PubMed] [Google Scholar]
  10. Doherty P. C. Quantitative studies of the inflammatory process in fatal viral meningoencephalitis. Am J Pathol. 1973 Dec;73(3):607–622. [PMC free article] [PubMed] [Google Scholar]
  11. Doherty P. C., Zinkernagel R. M. Quantitative studies of the growth and rejection of allogeneic tumour cells in mouse cerebrospinal fluid. Elimination in the absence of H-2 differences. Clin Exp Immunol. 1975 Feb;19(2):355–366. [PMC free article] [PubMed] [Google Scholar]
  12. Doherty P. C., Zinkernagel R. M., Ramshaw I. A., Grant C. K. Rejection of allogeneic tumor cells growing in mouse cerebrospinal fluid. Functional analysis of the inflammatory process. J Neuroimmunol. 1981 Mar;1(1):93–99. doi: 10.1016/0165-5728(81)90011-4. [DOI] [PubMed] [Google Scholar]
  13. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  14. Ensinger M. J. Isolation and genetic characterization of temperature-sensitive mutants of vaccinia virus WR. J Virol. 1982 Sep;43(3):778–790. doi: 10.1128/jvi.43.3.778-790.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. GLASGOW L. A., HABEL K. The role of interferon in vaccinia virus infection of mouse embryo tissue culture. J Exp Med. 1962 Mar 1;115:503–512. doi: 10.1084/jem.115.3.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gidlund M., Orn A., Wigzell H., Senik A., Gresser I. Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature. 1978 Jun 29;273(5665):759–761. doi: 10.1038/273759a0. [DOI] [PubMed] [Google Scholar]
  17. Gresser I., Guy-Grand D., Maury C., Maunoury M. T. Interferon induces peripheral lymphadenopathy in mice. J Immunol. 1981 Oct;127(4):1569–1575. [PubMed] [Google Scholar]
  18. Hapel A., Gardner I. Appearance of cytotoxic T cells in cerebrospinal fluid of mice with ectromelia virus-induced meningitis. Scand J Immunol. 1974;3(3):311–319. doi: 10.1111/j.1365-3083.1974.tb01262.x. [DOI] [PubMed] [Google Scholar]
  19. Heron I., Berg K., Cantell K. Regulatory effect of interferon on T cells in vitro. J Immunol. 1976 Oct;117(4):1370–1373. [PubMed] [Google Scholar]
  20. Hirsch M. S., Ellis D. A., Proffitt M. R., Black P. H. Effects of interferon on leukaemia virus activation in graft versus host disease. Nat New Biol. 1973 Jul 25;244(134):102–103. doi: 10.1038/newbio244102a0. [DOI] [PubMed] [Google Scholar]
  21. Howard R. J., Notkins A. L., Mergenhagen S. E. Inhibition of cellular immune reactions in mice infected with lactic dehydrogenase virus. Nature. 1969 Mar 1;221(5183):873–874. doi: 10.1038/221873a0. [DOI] [PubMed] [Google Scholar]
  22. Hurwitz J. L., Pan S., Wettstein P. J., Doherty P. C. Cross-reactivity patterns of vaccinia-specific cytotoxic T lymphocytes from H-2Kb mutants. Immunogenetics. 1983;17(1):79–87. doi: 10.1007/BF00364291. [DOI] [PubMed] [Google Scholar]
  23. Kern E. R., Glasgow L. A. Evaluation of interferon and interferon inducers as antiviral agents: animal studies. Pharmacol Ther. 1981;13(1):1–38. doi: 10.1016/0163-7258(81)90065-6. [DOI] [PubMed] [Google Scholar]
  24. Kiessling R., Klein E., Wigzell H. "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol. 1975 Feb;5(2):112–117. doi: 10.1002/eji.1830050208. [DOI] [PubMed] [Google Scholar]
  25. Kiessling R., Wigzell H. An analysis of the murine NK cell as to structure, function and biological relevance. Immunol Rev. 1979;44:165–208. doi: 10.1111/j.1600-065x.1979.tb00270.x. [DOI] [PubMed] [Google Scholar]
  26. Korngold R., Bennink J. R., Doherty P. C. Early dominance of irradiated host cells in the responder profiles of thymocytes from P leads to F1 radiation chimeras. J Immunol. 1981 Jul;127(1):124–129. [PubMed] [Google Scholar]
  27. Korngold R., Blank K. J., Murasko D. M. Effect of interferon on thoracic duct lymphocyte output: induction with either poly I:poly C or vaccinia virus. J Immunol. 1983 May;130(5):2236–2240. [PubMed] [Google Scholar]
  28. Korngold R., Doherty P. C. The localized primary cytotoxic T-cell response to cells expressing minor histocompatibility differences. Scand J Immunol. 1984 Feb;19(2):175–180. doi: 10.1111/j.1365-3083.1984.tb00914.x. [DOI] [PubMed] [Google Scholar]
  29. Krim M. Towards tumor therapy with interferons, Part I. Interferons: production and properties. Blood. 1980 May;55(5):711–721. [PubMed] [Google Scholar]
  30. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lindahl-Magnusson P., Leary P., Gresser I. Interferon inhibits DNA synthesis induced in mouse lymphocyte suspensions by phytohaemagglutinin or by allogeneic cells. Nat New Biol. 1972 May 24;237(73):120–121. doi: 10.1038/newbio237120a0. [DOI] [PubMed] [Google Scholar]
  32. Miörner H., Landström L. E., Larner E., Larsson I., Lundgren E., Strannegård O. Regulation of mitogen-induced lymphocyte DNA synthesis by human interferon of different origins. Cell Immunol. 1978 Jan;35(1):15–24. doi: 10.1016/0008-8749(78)90122-3. [DOI] [PubMed] [Google Scholar]
  33. Notkins A. L., Mergenhagen S. E., Howard R. J. Effect of virus infections on the function of the immune system. Annu Rev Microbiol. 1970;24:525–538. doi: 10.1146/annurev.mi.24.100170.002521. [DOI] [PubMed] [Google Scholar]
  34. Oehler J. R., Herberman R. B. Natural cell-mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidylic acid. Int J Cancer. 1978 Feb 15;21(2):221–229. doi: 10.1002/ijc.2910210214. [DOI] [PubMed] [Google Scholar]
  35. Owen J. A., Allouche M., Doherty P. C. Limiting dilution analysis of the specificity of influenza-immune cytotoxic T cells. Cell Immunol. 1982 Feb;67(1):49–59. doi: 10.1016/0008-8749(82)90198-8. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Schattner A., Meshorer A., Wallach D. Involvement of interferon in virus-induced lymphopenia. Cell Immunol. 1983 Jul 1;79(1):11–25. doi: 10.1016/0008-8749(83)90046-1. [DOI] [PubMed] [Google Scholar]
  38. VERLINDE J. D., KRET A. [On the formation of a substance with the characteristics of interferon in the brains of mice infected intracerebrally with vaccinia virus]. Acta Leiden. 1963;32:297–302. [PubMed] [Google Scholar]
  39. Zinkernagel R. M., Doherty P. C. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J Exp Med. 1973 Nov 1;138(5):1266–1269. doi: 10.1084/jem.138.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. de Maeyer E., Mobraaten L., de Maeyer-Guignard J. Prolongation par l'interféron de la survie des greffes de peau chez la souris. C R Acad Sci Hebd Seances Acad Sci D. 1973 Nov 12;277(19):2101–2103. [PubMed] [Google Scholar]

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