Genetic predisposition and environmental instructions tune thresholds for the activation, effector functions and lifespan of T cells, other inflammatory cells and resident tissue cells. Defects in apoptosis and peripheral tolerance in T cells define different allergic phenotypes. In individuals with atopic allergic disease, activated allergen-specific T cells expressing high levels of IFN-gamma predominantly undergo apoptosis in the circulation, skewing the immune response to surviving T helper type 2 (Th2) cells. In affected tissues, these cells switch on effector cytokines and induce the activation and apoptosis of epithelial cells. In individuals with non-atopic monoallergic disease, by contrast, a disturbed balance towards allergen-specific Th2 cells instead of T regulatory type 1 (Tr1) cells characterizes the T cell response.