Immune dysregulation in allergic respiratory disease: the role of T regulatory cells

Although earlier research focused on the role of the polarity of T helper cell signalling as the defining factor in immune responses, it is now recognised that other cells with regulatory properties have a more key role. It has been recently proposed that allergic disease may result from an inappropriate balance between regulatory cells (including but not limited to CD4+ CD25+ T regulatory cells) and T helper type 2 (Th2) effector cells. In the airways, a number of other cells also have important regulatory effects on local immune responses, including epithelial cells and airway dendritic cells (DC). Allergic respiratory disease appears to be the culmination of both local epithelial dysfunction and generalised immune dysregulation resulting in Th2 propensity (atopic predisposition). Although these processes are related they also appear to occur independently. This review examines evolving models of allergy pathogenesis, including the newly recognised role of diverse groups of regulatory cells. Increasing rates of allergic disease (and other immune diseases) suggest that environmental changes may be having fundamental effects on common regulatory pathways. Understanding these influences and their mechanism of action could lead to strategies to prevent disease.