Pneumologie 2014; 68 - A83
DOI: 10.1055/s-0034-1376852

A novel mouse model for the investigation of adaptive immune responses upon de novo antigen expression in lung epithelial cells

M Riehn 1, M Cebula 1, A Ochel 1, P Gaur 1, H Hauser 1, D Wirth 1
  • 1Helmholtz Centre for Infection Research, Braunschweig

Upon infection, viral antigen presentation is accompanied with activation of innate immunity which shapes the adaptive immune response and in particular the T cell response. We aimed at developing a mouse model to induce immune mediated lung damage to better understand the mechanisms involved in lung regeneration.

For this purpose, we mated SPCCre mice in which the CreERT2 recombinase is expressed in lung alveolar type II epithelial cells (Rock et al., 2011) to RosaOva transgenic mice (Sandhu et al., 2011). In the resulting double transgenic mice Tamoxifen induced Cre recombination results in de novo OVA expression in about 50% cells. We employed a reporter mouse model SPCCre x ROSALuc to monitor the time course of activation of the Cre recombinase specifically in vivo in lung. To evaluate the T cell response upon antigen expression, we generated SPCCre x ROSA Ova x OT-I mice. In this model, the intracellular neo-antigen Ova is induced in alveolar type II cells of the lung in presence of Ova antigen specific CD8 T cells (OT-I). Upon Tamoxifen mediated induction of antigen we observed massive infiltration of lymphocytes as documented by histological analysis. Interestingly, this T cell infiltration was transient, suggesting OT-I cell mediated destruction of alveolar type II cells followed by regeneration of lung tissue. These findings indicate the potential of the model to investigate T-cell response, antigen clearance and reconstitution of respiratory tissue independently of the innate immune induction in the full-fledged adaptive immune system.

References:

Rock, J. R. and B. L. Hogan (2011). "Epithelial progenitor cells in lung development, maintenance, repair, and disease." Annu Rev Cell Dev Biol 27: 493 – 512.

Sandhu, U., et al. (2011). "Strict control of transgene expression in a mouse model for sensitive biological applications based on RMCE compatible ES cells." Nucleic Acids Res 39(1): e1.