IL-12 treatment attenuates T helper cell type 2 and B cell responses but does not improve vaccine-enhanced lung illness

T Hussell, U Khan, P Openshaw
1997 Journal of Immunology  
In humans and mice, sensitization to 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, the precise roles of different functional subsets are unknown, and no protective nonpathogenic subset has been defined. BALB/c mice sensitized to the major surface glycoprotein of RSV (G) expressed by recombinant vaccinia virus develop
more » ... driven lung eosinophilia after intranasal challenge with RSV. In an attempt to manipulate the outcome of vaccination, we treated 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 the total lymphoid cell infiltration into the alveolar space. Analysis of intracellular cytokines by flow cytometry 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. Treatment with IL-12 reduced this figure to approximately 1.5%. Although IL-12 treatment reduced lung eosinophilia, illness (as assessed by weight loss) was not eliminated and, in some experiments, was increased. The present study shows that reversing Th2-associated pathology with IL-12 does not necessarily benefit the host.
doi:10.4049/jimmunol.159.1.328 fatcat:v47kxzndqzdonmarx6rkurimoy