Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus

  • Cannon M
  • Openshaw P
  • Askonas B
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Abstract

Respiratory syncytial virus (RSV) is an ubiquitous paramyxovirus belonging to the genus Pneumovirus (1). Natural human RSV infections occur in winter outbreaks, usually resulting in common cold syndrome. Infants are especially prone to lower respiratory tract infection, which is the most common single cause of hospitalization ofthis age group in industrial countries. Vaccination with formaldehyde-inactivated RSV induces neutralizing serum antibodies, but fails to protect against natural in- fection; moreover, infected vaccinees suffer exacerbated lung disease. Similarly vac- cinated cotton rats show enhanced pathological changes in the lungs (2), as do mice primed with recombinant vaccinia viruses expressing single RSV proteins (3). These methods of priming induce both humoral and cellular immune responses to RSV (2-5). Passive transfer of mAbs has not been shown to enhance pathology in RSV infected mice, and some antibodies protect against pulmonary disease (6, 7) . Cell- mediated immunity may therefore play a role in the pathogenesis of RSV-induced disease. Although polyclonal memory Tcells can clear persistent RSV infection in immunodeficient mice (8), the role of T cell subpopulations in immunopathology merits examination. In this study, we use bronchoalveolar lavage (BAL)to monitor pulmonary disease in RSV-infected mice, and show enhanced pathology associated with accelerated clear- ance of lung virus after intravenous transfer of a cytotoxic RSV-specific T cell line and a CTL clone.

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Authors

  • MJ Cannon

  • PJM Openshaw

  • BA Askonas

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