Differential regulation of Th2 and Th1 lung inflammatory responses by protein kinase Cθ

In vitro and recent in vivo studies have identified protein kinase CO (PKCO) as an important intermediate in signaling pathways leading to T cell activation, proliferation, and cytokine production. However, the importance of PKCO to many T cell-driven inflammatory responses has not been demonstrated. In this study we show that although PKCO is required for the development of a robust lung inflammatory response controlled by Th2 cells, it plays a lesser role in the development of a similar lung inflammatory response -controlled by Th1 cells. PKCO-deficient mice were strongly compromised in generating Th2 cells and exhibited reduced airway eosinophilia and Th2 cytokine production in lungs. PKCO was required for the initial development of Th1 cells, with these cells exhibiting delayed kinetics of differentiation and accumulation. However, with recall Ag challenge via the airways, this defect was overcome, and lung infiltration and Th1 cytokine production were largely unimpaired in PKCOdeficient animals. These data suggest that PKCO can play roles in aspects of both Th2 and Th1 responses, but lung inflammation induced by Th2 cells is more dependent on this protein kinase than lung inflammation induced by Th1 cells.