1887

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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1998-07-01
2021-10-22
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