The role of lymphocytes in allergic disease.

In the last few years strong evidence has accumulated to suggest that allergen-reactive type-2 T helper (T(H)2) cells play an important role in the induction and maintenance of the allergic inflammatory cascade. First, cytokines and chemokines produced by T(H)2 cells (GM-CSF, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, macrophage-derived chemokine) and those produced by other cell types in response to T(H)2 cytokines or as a reaction to T(H)2-related tissue damage (eotaxin, transforming growth factor-beta, IL-11) account for most pathophysiologic aspects of allergic disorders (production of IgE antibodies; recruitment or activation of mast cells, basophils, and eosinophils; mucus hypersecretion; subepithelial fibrosis; and tissue remodeling). The T(H)2 hypothesis may also explain the complex genetic background responsible for allergic disorders. Several genes are involved in the development and regulation of T(H)2 cells and may provide the reason why the prevalence of atopic allergy is increasing in Western countries. Indeed, a dramatic change has occurred in the last several decades in the "microbial" environment of children, thus probably altering the balance between T(H)1 and T(H)2 responses to "innocuous" antigens (allergens) in favor of T(H)2 responses. Finally, the T(H)2 hypothesis offers exciting opportunities for the development of novel immunotherapeutic strategies targeted to address allergen-specific T(H)2 cells or T(H)2-derived effector molecules in atopic individuals.