IL-12 TREATMENT ATTENUATES T-HELPER-CELL-TYPE-2 AND B-CELL RESPONSES BUT DOES NOT IMPROVE VACCINE-ENHANCED LUNG ILLNESS

In humans and mice, sensitization ia respiratory syncytial virus (RSV) Ags can result in severe inflammatory lung disease during subsequent infection with RSV. Although specific antiviral T cells are thought to be responsible for this augmentation of disease, tile precise roles o f different: functional subsets are unknown, and no protective nonpath ogenic subset has been defined, BALB/c mice sensitized to fl-re major surface glycoprotein of RSV (G) expressed by recombinant vaccinia viru s develop Th2-driven lung eosinophilia after intranasal challenge wilt ? RSV. In an attempt to manipulate the outcome of vaccination, we trea ted mice with IL-12 at various times during vaccination and challenge. IL-12 treatment reduced the vaccine-induced lung eosinophilia during RSV challenge, but increased tile total lymphoid cell infiltration int o the alveolar space, Analysis of intracellular cytokines by flow cyto metry showed that IFN-gamma production during challenge was increased, and IL-4 and IL-5 levels were reduced by IL-12 treatment, in control treated mice, 40 to 50% of the lung lymphoid cells were B cells, Treat ment with IL-12 reduced this figure to approximately 1.5%. Although IL -12 treatment reduced lung eosinophilia, illness (as assessed by weigh t toss) was not eliminated and, in some experiments, was increased, Th e present study shows that reversing Th2-associated pathology with IL- 12 does not necessarily benefit the host.