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 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 Th2-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.
Hussell
T
T
Department of Respiratory Medicine, Imperial College School of Medicine, St. Mary's Hospital, Paddington, London, United Kingdom.
Khan
U
U
Openshaw
P
P
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D018664:Interleukin-12 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D018664:Interleukin-12