T-cell subsets in the pathogenesis of human asthma.

Genetic predisposition and environmental instructions tune thresholds for activation of T cells, other inflammatory cells, and resident tissue cells in asthmatic inflammation. Selective migration of peripheral-blood T cells to the lungs, their survival and reactivation in the submucosa, and their effector functions represent sequential immunologic events. Activation-induced T-cell death and peripheral T-cell tolerance are critical events in disease pathogenesis. As a mechanism for peripheral Th2 response in atopic diseases, particularly, the high interferon (IFN)-gamma-producing Th1 compartment of activated effector T cells shows increased activation-induced cell death, skewing the immune response toward surviving Th2 cells in allergic asthma. After migration to asthmatic lung, these cells switch on effector cytokines and induce bronchial epithelial apoptosis with mainly IFN-gamma, tumor necrosis factor (TNF)-alpha, and Fas-ligand. In addition, skewing of allergen-specific effector T cells to T-regulatory cells appears to be an essential event in the control of harmful immune response induced by allergens as a possible means for remedy.