ABUNDANT IFN-GAMMA PRODUCTION BY LOCAL T-CELLS IN RESPIRATORY SYNCYTIAL VIRUS-INDUCED EOSINOPHILIC LUNG-DISEASE

Respiratory syncytial virus (RSV) is a frequent cause of severe lung d isease in young children, Primed T cells are required for virus cleara nce, but are causally implicated in the enhanced pathology seen follow ing RSV infection of some infants and experimental animals vaccinated against the virus. In BALB/c mice, vaccination with recombinant vaccin ia virus expressing the viral attachment protein (G) leads to pulmonar y eosinophilia during subsequent infection, which indirect evidence su ggests may be due to CD4(+) Th2 cells. The production of IFN-gamma, IL -2, -4, -5 and -10 cytokine mRNA by RT-PCR and intracellular cytokines by Row cytometry following RSV challenge of vaccinated mice were ther efore compared. Lung eosinophilia was associated with enhanced local r ecruitment of CD4(+) cells in G sensitized mice, while CD8(+) cells do minated in mice vaccinated with the viral fusion protein (F) or second matrix protein (M2). Lung eosinophilia was also associated with a loc alized reduction in IFN-gamma and increased IL-4 and IL-5 mRNA transcr iption as well as elevated RSV specific IgG1 antibody production. Th2 cytokine protein production by T cells showed no apparent change. Alth ough IFN-gamma production diminished in eosinophilic mice, it remained the major cytokine found in lung T cells. It was concluded that lung eosinophilia can develop despite abundant IFN-gamma production by loca l T cells, but is associated with a shift in the balance between Th2 a nd Th1 cytokine production.