1887

Abstract

Interferon gamma (IFN) represents an essential cytokine involved in murine cytomegalovirus (MCMV) clearance from the salivary gland and the control of horizontal transmission. Because IFN cannot be responsible for all cytokine effects during recovery from MCMV infection we have now tested the potential participation of tumour necrosis factor alpha (TNF) in the antiviral defence. Neutralization of endogenous TNF abolished the antiviral activity of CD4 T cells in immunocompetent as well as in CD8 subset-deficient mice. These data suggest that the antiviral effect of the CD4 subset requires the presence of at least two cytokines, namely IFN and TNF. Depletion of endogenous TNF in adoptive cell transfer recipients diminished the antiviral function of CD8 T lymphocytes suggesting that TNF also participates in CD8 T cell effector functions. Furthermore, endogenous cytokines were found to be required for survival after infection with lethal doses of MCMV, whereas immunotherapy with recombinant TNF and IFN could not limit virus replication . The results suggest that, similar to IFN, TNF is an integral part of the protective mechanisms involved in cytomegalovirus clearance.

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1993-10-01
2024-12-05
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References

  1. Ammann A. J., Palladino M. A., Volberding P., Abrams D., Martin N. L., Conant M. 1987; Tumor necrosis factor alpha and beta in acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Journal of Clinical Immunology 7:481–185
    [Google Scholar]
  2. Asher A. L., Mule J. J., Kasid A., Restifo N. P., Salo J. C., Reichert C. M., Jaffe G., Fendly B., Kriegler M., Rosenberg S. A. 1991; Murine tumor cells transduced with the gene for tumor necrosis factor-a. Evidence for paracrine immune effects of tumor necrosis factor against tumors. Journal of Immunology 146:3227–3234
    [Google Scholar]
  3. Bukowski J. F., Warner J. F., Dennert G., Welsh R. M. 1985; Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo. Journal of Experimental Medicine 161:40–52
    [Google Scholar]
  4. Chen W., Havell E. A., Harmsen A. G. 1992; Importance of endogenous tumor necrosis factor alpha and gamma interferon in host resistance against Pneumocystis carinii infection. Infection and Immunity 60:1279–1284
    [Google Scholar]
  5. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. 1984; Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature, London 312:548–550
    [Google Scholar]
  6. Del Val M., Munch K., Reddehase M. J., Koszinowski U. H. 1989; Presentation of cytomegalovirus immediate-early antigen to cytolytic T lymphocytes is selectively blocked by viral genes expressed in the early phase. Cell 58:305–315
    [Google Scholar]
  7. Del Val M., Schlicht H.-J., Ruppert T., Reddehase M. J., Koszinowski U. H. 1991a; Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell 66:1145–1153
    [Google Scholar]
  8. Del Val M., Schlicht H.-J., Volkmer H., Messerle M., Reddehase M. J., Koszinowski U. H. 1991b; Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. Journal of Virology 65:3641–3646
    [Google Scholar]
  9. Doherty P. C., Allan W., Eichelberger M. 1992; Roles of αβ and γ T cell subsets in viral immunity. Annual Review of Immunology 10:123–151
    [Google Scholar]
  10. Drew W. L. 1988; Cytomegalovirus infection in patients with AIDS. Journal of Infectious Diseases 158:449–456
    [Google Scholar]
  11. Havell E. A. 1987; Production of tumor necrosis factor during murine listeriosis. Journal of Immunology 139:4225–4231
    [Google Scholar]
  12. Johnson L. L. 1992; A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection. Infection and Immunity 60:1979–1983
    [Google Scholar]
  13. Jonjić S., Del Val M., Keil G. M., Reddehase M. J., Koszinowski U. H. 1988; A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection. Journal of Virology 62:1653–1658
    [Google Scholar]
  14. Jonjić S., Mutter W., Weiland F., Reddehase M. J., Koszinowski U. H. 1989; Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. Journal of Experimental Medicine 169:1199–1212
    [Google Scholar]
  15. Jonjić S., Pavic I., Lucin P., Rukavina D., Koszinowski U. H. 1989; Efficacious control of cytomegalovirus infection after longterm depletion of CD8+ T lymphocytes. Journal of Virology 64:5457–5464
    [Google Scholar]
  16. Karupiah G., Blanden R. V., Ramshaw I. A. 1990; Interferon-γ is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection. Journal of Experimental Medicine 172:1495–1503
    [Google Scholar]
  17. Kirkpatrick C. H., Davis K. C., Horsburg C. R. Jr, Cohn D. L., Penley K., Judson F. N. 1985; Interleukin-2 production by persons with the generalized lymphadenopathy syndrome or the acquired immune deficiency syndrome. Journal of Clinical Immunology 5:31–37
    [Google Scholar]
  18. Klavinskis L. S., Geckeler R., Oldstone M. B. A. 1989; Cytotoxic T lymphocyte control of acute lymphocytic choriomeningitis virus infection: interferon y, but not tumour necrosis factor a, displays antiviral activity in vivo. Journal of General Virology 70:3317–3325
    [Google Scholar]
  19. Kohonen-Corish M. R. J., King N. J. C., Woodhams C. E., Ramshaw I. A. 1990; Immunodeficient mice recover from infection with vaccinia virus expressing interferon y. European Journal of Immunology 20:157–161
    [Google Scholar]
  20. Koszinowski U. H., Del Val M., Reddehase M. J. 1990; Cellular and molecular basis of the protective immune response tocytomegalovirus infection. Current Topics in Microbiology and Immunology 154:189–220
    [Google Scholar]
  21. Koszinowski U. H., Reddehase M. J., Del Val M. 1992; Principles of cytomegalovirus antigen presentation in vitro and in vivo. Seminars in Immunology 4:71–79
    [Google Scholar]
  22. Larrick J. W., Wright S. C. 1990; Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB Journal 4:3215–3223
    [Google Scholar]
  23. Leist T. P., Eppler M., Zinkernagel R. M. 1989; Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-gamma interferon-treated mice. Journal of Virology 63:2813–2819
    [Google Scholar]
  24. Lucin P., Pavic I., Polic B., Jonjic S., Koszinowski U. H. 1992; Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands. Journal of Virology 66:1977–1984
    [Google Scholar]
  25. Meyers J. D. 1984; Cytomegalovirus infection following marrow transplantation: risk, treatment, prevention. Birth Defects Original Articles Series 20:101–104
    [Google Scholar]
  26. Mosmann T. R., Moore K. W. 1991; The role of IL-10 in crossregulation of Thl and Th2 responses. Immunology Today 12:A49–A53
    [Google Scholar]
  27. Murray H. W., Rubin B. Y., Masur H., Roberts R. B. 1984; Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. New England Journal of Medicine 310:883–889
    [Google Scholar]
  28. Nauciel C., Espinasse-Maes F. 1992; Role of gamma interferon and tumor necrosis factor alpha in resistance to Salmonella typhimurium infection. Infection and Immunity 60:450–454
    [Google Scholar]
  29. Ohara J., Paul W. E. 1985; Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature, London 315:333–336
    [Google Scholar]
  30. Quinnan G. V., Manischewitz J. F. 1987; Genetically determined resistance to lethal murine cytomegalovirus infection is mediated by interferon-dependent and -independent restriction of virus replication. Journal of Virology 61:1875–1881
    [Google Scholar]
  31. Ramshaw I., Ruby J., Ramsay A., Ada G., Karupiah G. 1992; Expression of cytokines by recombinant vaccinia viruses: a model for studying cytokines in virus infections in vivo. Immunological Reviews 127:157–183
    [Google Scholar]
  32. Reddehase M. J., Koszinowski U. H. 1984; Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection. Nature, London 312:369–371
    [Google Scholar]
  33. Reddehase M. J., Weiland F., Munch K., Jonjic S., Luske A., Koszinowski U. H. 1985; Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. Journal of Virology 55:264–273
    [Google Scholar]
  34. Reddehase M. J., Mutter W., Munch K., Buhring H.-J., Koszinowski U. H. 1987; CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. Journal of Virology 61:3102–3108
    [Google Scholar]
  35. Reddehase M. J., Jonjic S., Weiland F., Mutter W., Koszinowski U. H. 1988; Adoptive immunotherapy of murine cytomegalovirus adrenalitis in the immunocompromised host: CD4-helper-independent antiviral function of CD8-positive memory T lymphocytes derived from latently infected donors. Journal of Virology 62:1061–1065
    [Google Scholar]
  36. Reddehase M. J., Rothbard J. B., Koszinowski U. H. 1989; A pentapeptide as a minimal antigenic determinant for MHC-class I-restricted T lymphocytes. Nature, London 337:651–653
    [Google Scholar]
  37. Rossol-Voth R., Rossol S., Schutt K. H., Corridori S., de Cian W., Falke D. 1991; In vivo protective effect of tumour necrosis factor a against experimental infection with herpes simplex virus type 1. Journal of General Virology 72:143–147
    [Google Scholar]
  38. Sambhi S. K., Kohonen-Corish M. R. J., Ramshaw I. A. 1991; Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo. Proceedings of the National Academy of Sciences, U,. S,. A 88:4025–1029
    [Google Scholar]
  39. Silva C. L., Faccioli L. H. 1992; Tumor necrosis factor and macrophage activation are important in clearance of Nocardia brasiliensis from the livers and spleens of mice. Infection and Immunity 60:3566–3570
    [Google Scholar]
  40. Soike K. F., CzARNrecKi C. W., Baskin G., Blanchard J., Liggitt D. 1989; Enhancement of simian varicella virus infection in African green monkeys by recombinant human tumor necrosis factor alpha. Journal of Infectious Diseases 159:331–335
    [Google Scholar]
  41. Spitalny G. L., Havell E. A. 1984; Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. Journal of Experimental Medicine 159:1560–1565
    [Google Scholar]
  42. Stagno S., Pass R. F., Cloud G., Britt W. J., Henderson R. E., Walton P. D., Veren D. A., Page F., Alford C. A. 1986; Primary cytomegalovirus infection in pregnancy: incidence, transmission to fetus and clinical outcome. Journal of the American Medical Association 256:1904–1908
    [Google Scholar]
  43. Sypek J. P., Wyler D. J. 1991; Antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on CD4+ T lymphocyte plasma membrane. Journal of Experimental Medicine 174:755–759
    [Google Scholar]
  44. Titus R. G., Sherry B., Cerami A. 1989; Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. Journal of Experimental Medicine 170:2097–2104
    [Google Scholar]
  45. Titus R. G., Sherry B., Cerami A. 1991; The involvement of TNF, IL-1 and IL-6 in the immune response to protozoan parasites. In Immunoparasitology Today pp 13–16 Edited by Ash C., Gallagher R. B. Cambridge: Elsevier;
    [Google Scholar]
  46. Volkmer H., Bertholet C., Jonjic S., Witter S. R., Koszinowski U. H. 1987; Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus. Journal of Experimental Medicine 166:668–677
    [Google Scholar]
  47. Walker B. D., Chakrabarti S., Moss B., Paradis T. J., Flynn T., Durno A. G., Blumberg R. S., Kaplan J. C., Hirsch M. S., Schooley R. T. 1987; HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature, London 328:345–348
    [Google Scholar]
  48. Wang A. M., Creasey A. A., Ladner M. B., Lin L. S., Strickler J., Vanarsdell J. N., Yamamoto R., Mark D. F. 1985; Molecular cloning of the complementary DNA for human tumor necrosis factor. Science 228149–154
    [Google Scholar]
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