Transgenic expression of survivin compensates for OX40‐deficiency in driving Th2 development and allergic inflammation

Survivin, an inhibitor of apoptosis family molecule, has been proposed as a crucial intermediate in the signaling pathways leading to T‐cell development, proliferation, and expansion. However, the importance of survivin to T‐cell‐driven inflammatory responses has not been demonstrated. Here, we show that survivin transgenic mice exhibit an increased antigen‐driven Th2 lung inflammation and that constitutive expression of survivin reversed the defective lung inflammation even in the absence of OX40 costimulation. We found that OX40‐deficient mice were compromised in generating Th2 cells, airway eosinophilia, and IgE responses. In contrast, OX40‐deficient/survivin transgenic mice generated normal Th2 responses and exhibited strong lung inflammation. These results suggest that OX40 costimulation crucially engages survivin during antigen‐mediated Th2 responses. These findings also promote the notion that OX40 costimulation regulates allergic responses or lung inflammation by targeting survivin thereby enhancing T‐cell proliferation and resulting in more differentiated Th2 cells in the allergic inflammatory response.