The central rôle of T-cells in allergic sensitization and IgE regulation

The atopic phenotype develops on the basis of a genetic predisposition. Several candidate genes and chromosomal regions have been recently identified that may play a rôle in the development of allergic sensitization and total IgE production, including genes encoding MHC and T-cell receptor (TCR) molecules, cytokines and others. Genetic predisposition triggers and immunological dysregulation which is controlled by CD4+ T-cells. (Specialized) antigen presenting cells process and present allergenic peptides (T-cell epitopes) on MHC class II molecules to T-cells that recognize MHC plus peptide using the TCR. Cognate and non-cognate interaction results in T-cell activation. Selective stimulation of the allergen specific T-cells is the result of allergen-specific sensitization. These T-cells are characterized by (simultaneous) production of IL-3, IL-4, IL-5 (and may be IL-13). These cytokines control the production of IgE by B cells and play a critical rôle in the activation and differentiation of effector cells of the allergic response (such as eosinophils and mast cells). In addition to MHC-TCR interaction and cytokine production, ligation of CD40 and CD40L represents an additional requirement for the production of functional IgE molecules. Immediate hypersensitivity responses are characterized by an early phase response (triggered by many mediators released from effector cells following allergen exposure, IgE cross-linking and activation of signal transduction pathways) and a late phase response that is mediated to a large extend by the influx of T-cells and effector cells into the site of allergic inflammation. Deliniation of the immunological mechanisms that result in allergic sensitization will contribute to the development of specific immunomodulatory strategies aimed to prevent the development of allergies.