1887

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Volume 79, Issue 7

Abundant IFN-μ production by local T cells in respiratory syncytial virus-induced eosinophilic lung disease Free

Abstract

Respiratory syncytial virus (RSV) is a frequent cause of severe lung disease in young children. Primed T cells are required for virus clearance, but are causally implicated in the enhanced pathology seen following RSV infection of some infants and experimental animals vaccinated against the virus. In BALB/c mice, vaccination with recombinant vaccinia virus expressing the viral attachment protein (G) leads to pulmonary eosinophilia during subsequent infection, which indirect evidence suggests may be due to CD4 Th2 cells. The production of IFN-γ, IL- 2, −4, −5 and −10 cytokine mRNA by RT-PCR and intracellular cytokines by flow cytometry following RSV challenge of vaccinated mice were therefore compared. Lung eosinophilia was associated with enhanced local recruitment of CD4 cells in G sensitized mice, while CD8 cells dominated in mice vaccinated with the viral fusion protein (F) or second matrix protein (M2). Lung eosinophilia was also associated with a localized reduction in IFN-γ and increased IL-4 and IL-5 mRNA transcription as well as elevated RSV specific IgG1 antibody production. Th2 cytokine protein production by T cells showed no apparent change. Although IFN-γ production diminished in eosinophilic mice, it remained the major cytokine found in lungT cells. It was concluded that lung eosinophilia can develop despite abundant IFN-γ production by local T cells, but is associated with a shift in the balance between Th2 and Th1 cytokine production.

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© Society for General Microbiology 1998
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1998-07-01
2024-04-20
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References

  1. Alwan W. H., Openshaw P. J. M. 1993; Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. Vaccine 11:431–437
     [Google Scholar]
  2. Alwan W. H., Record F. M., Openshaw P. J. M. 1992; CD4 + T cells clear virus but augment disease in mice infected with respiratory syncytial virus: comparison with the effects of CD8+ cells. Clinical and Experimental Immunology 88:527–536
     [Google Scholar]
  3. Alwan W. H., Record F. M., Openshaw P. J. M. 1993; Phenotypic and functional characterisation of T cell lines specific to individual respiratory syncytial virus proteins. Journal of Immunology 150:5211–5218
     [Google Scholar]
  4. Alwan W. H., Kozlowska W. J., Openshaw P. J. 1994; Distinct types of lung disease caused by functional subsets of antiviral T cells. Journal of Experimental Medicine 179:81–89
     [Google Scholar]
  5. Cannon M. J., Openshaw P. J. M., Askonas B. A. 1988; Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. Journal of Experimental Medicine 168:1163–1168
     [Google Scholar]
  6. Chin J., Magoffin R. L., Shearer L. A., Schieble J. H., Lennette E. H. 1969; Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. American Journal of Epidemiology 89:449–463
     [Google Scholar]
  7. Cockfield S. M., Ramassar V., Noujaim J., Van der Meide P. H., Halloran P. F. 1993; Regulat ion of IFN-gamma expression in vivo: IFN-gamma up-regulates expression of its mRNA in normal and lipopolysaccharide-stimulated mice. Journal ofImmunology 150:717–725
     [Google Scholar]
  8. Connors M., Kulkarni A. B., Collins P. L., Firestone C. Y., Holmes K. L., Morse H. C., Murphy B. R. 1992; Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein (Vac-M2) is mediated by CD8+ T cells, while that induced by Vac-F or Vac-G recombinants is mediated by antibodies. Journal of Virology 66:1277–1281
     [Google Scholar]
  9. Connors M., Giese N. A., Kulkarni A. B., Firestone C.-Y., Morse H. C.III Murphy B. R. 1994; Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin- inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. Journal of Virology 68:5321–5325
     [Google Scholar]
  10. Doherty P. C. 1995; Anatomical environment as a determinant in viral immunity. Journal of Immunology 155:1023–1027
     [Google Scholar]
  11. Gordon J. R., Burd P. R., Galli S. J. 1990; Mast cells as a source of multifunctional cytokines. Immunology Today 11:458–464
     [Google Scholar]
  12. Graham B. S., Bunton L. A., Wright P. F., Karzon D. T. 1991; Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. Journal ofClinical Investigation 88:1026–1033
     [Google Scholar]
  13. Halloran P. F., Autenried P., Ramassar V., Urmson J., Cockfield S. 1992; Local T cell responses induce widespread MHC expression: evidence that IFN-gamma induces its own expression in remote sites. Journal of Immunology 148:3837–3846
     [Google Scholar]
  14. Heilman C. A. 1990; From the National Institute of Allergy and Infectious Diseases and the World Health Organization: respiratory syncytial and parainfluenza viruses. Journal of Infectious Diseases 161:402–406
     [Google Scholar]
  15. Hussell T., Spender L. C., Georgiou A., O’Garra A., Openshaw P. J. M. 1996; Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus. Journal of General Virology 77:2447–2455
     [Google Scholar]
  16. Hussell T., Khan U., Openshaw P. J. M. 1997; IL-12 treatment attenuates T helper cell type 2 and B cell responses but does not improve vaccine-enhanced lung illness. Journal of Immunology 159:328–334
     [Google Scholar]
  17. Jackson M., Scott R. 1996; Different patterns of cytokine induction in cultures of respiratory syncytial (RS) virus-specific human TH cell lines following stimulation with RS virus and RS virus proteins. Journal of Medical Virology 49:161–169
     [Google Scholar]
  18. Kapikian A. Z., Mitchell R. H., Chanock R. M., Shvedoff R. A., Stewart C. E. 1969; An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. American Journal of Epidemiology 89:405–421
     [Google Scholar]
  19. Kim H. W., Canchola J. G., Brandt C. D., Pyles G., Chanock R. M., Jensen K., Parrott R. H. 1969; Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. American Journal of Epidemiology 89:422–434
     [Google Scholar]
  20. Mosmann T. R., Coffman R. L. 1989; Heterogeneity of cytokine secretion patterns and functions of helper T cells. Advances in Immunology 46:111–148
     [Google Scholar]
  21. Openshaw P. J. M., Anderson K., Wertz G. W., Askonas B. A. 1990; The 22-kilodalton protein of respiratory syncytial virus is a major target for Kd-restricted cytotoxic T lymphocytes from mice primed by infection. Journal of Virology 64:1683–1689
     [Google Scholar]
  22. Openshaw P. J. M., Clarke S. L., Record F. M. 1992; Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. International Immunology 4:493–500
     [Google Scholar]
  23. Openshaw P., Murphy E. E., Hosken N. A., Maino V., Davis K., Murphy K., O’Garra A. 1995; Heterogeneity ofintracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations. Journal of Experimental Medicine 182:1357–1367
     [Google Scholar]
  24. Srikiatkhachorn A., Braciale T. J. 1997a; Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection. Journal of Virology 71:678–685
     [Google Scholar]
  25. Srikiatkhachorn A., Braciale T. J. 1997b; Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. Journal of Experimental Medicine 186:421–432
     [Google Scholar]
  26. Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. 1988; Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 334:255–258
     [Google Scholar]
  27. Stott E. J., Ball L. A., Young K. K., Furze J., Wertz G. W. 1986; Human respiratory syncytial virus glycoprotein G expressed from recombinant vaccinia virus vector protects mice against live virus challenge. Journal of Virology 60:607–613
     [Google Scholar]
  28. Stott E. J., Taylor G., Ball L. A., Anderson K., Young K. K., King A. M. Q., Wertz G. W. 1987; Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus. Journal of Virology 61:3855–3861
     [Google Scholar]
  29. Tang Y. W., Graham B. S. 1995; Interleukin-12 treatment during immunization elicits a T helper cell type 1-like immune response in mice challenged with respiratory syncytial virus and improves vaccine immunogenicity. Journal of Infectious Diseases 172:734–738
     [Google Scholar]
  30. Taylor G., Stott E. J., Hughes M., Collins A. P. 1984; Respiratory syncytial virus infection in mice. Infection and Immunity 43:649–655
     [Google Scholar]
  31. Waris M. E., Tsou C., Erdman D. D., Zaki S. R., Anderson L. J. 1996; Respiratory syncytial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern. Journal of Virology 70:2852–2860
     [Google Scholar]
  32. Wertz G. W., Stott E. J., Young K. K. J., Anderson K., Ball L. A. 1987; Expression of the fusion protein of human respiratory syncytial virus from recombinant vaccinia virus vectors and protection of vaccinated mice. Journal of Virology 61:293–301
     [Google Scholar]
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Abundant IFN-μ production by local T cells in respiratory syncytial virus-induced eosinophilic lung disease
J. Gen. Virol. 79, 1751 (1998); https://doi.org/10.1099/0022-1317-79-7-1751
/content/journal/jgv/10.1099/0022-1317-79-7-1751
/content/journal/jgv/10.1099/0022-1317-79-7-1751
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