Characterization of Th2 Induced Bronchial Associated Lymphoid Tissue (BALT) in a Mouse Model of Asthma

Rationale: Lymphoid tissues in the lung are poorly appreciated compared with their counterparts in other tissues such as gut and skin. Inducible Bronchial associated lymphoid tissue (iBALT) has been demonstrated in response to influenza infection and neonatal exposure to bacterial products. By transfer of Th2 polarized transgenic CD4 T cells we have produced a localized lung inflammatory response that is characterized by hyper-eosinophilia, smooth muscle and goblet cell hyperplasia and the formation of iBALT. In this study we sought to characterize Th2 cell associated iBALT.

Methods: Mice were transferred with Th2 polarized transgenic CD4 T cells and challenged intranasally with recombinant allergen three times weekly for 3 weeks. Lungs were removed and paraffin embedded sections cut and stained with Hematoxylin and Eosin, Periodic Acid Schiff’’s or Masson’s Trichrome. Frozen lung sections were stained with florescence tagged anti-CD3, anti B220 and anti-CD11c monoclonal antibodies. Mice were treated with anti-IL-4/IL-13 monoclonal antibodies weekly.

Results: Within 15 minutes of the fourth challenge mice exhibited breathing difficulties accompanied by a sharp fall in temperature (from 37C to 30C). iBALT was detected in all challenged mice and found to contain B cells, T cells and dendritic cells. Neutralizing anti-IL-4/IL-13 inhibited inflammation by over 80% and reduced the number and size of iBALT by over 50%

Conclusions: Th2 cytokine dependent iBALT is present in the lungs of severely allergic mice that are similar to those described following influenza infection. Prevention of Th2 iBALT formation represents a promising new target for asthma therapy.