The Immune Response to Intrinsic and Extrinsic Allergens: Determinants of Allergic Disease

A central role for Th2 effector cells in IgE-mediated allergic disease is well established. However, the question of why some individuals develop allergic disease and others do not remains largely unanswered. Until recently, the prevailing view was that the allergic response reflected a shift in the Th1/Th2 'balance' to favor production of Th2 cytokines and IgE antibody isotype switching. Evidence is now emerging to suggest that distinct allergic responses cannot be distinguished simply on the basis of type 1 and type 2 cytokine profiles. For example, delayed-type hypersensitivity responses to intrinsic allergens derived from the dermatophyte fungus Trichophyton are associated with a paradoxical increase in Th2 cytokines compared with immediate hypersensitivity responses. In contrast, analysis of 'tolerant' responses to extrinsic allergens which are induced by specific immunotherapy or high-dose natural exposure to inhaled allergen (the modified Th2 response) supports a role for both the Th1 cytokine IFN-gamma and the regulatory cytokine IL-10. However, IL-10 may also be a critical mediator in the allergic response. In this article, we examine how analysis of epitope-specific T cell responses may lead to an understanding of how T lymphocyte cytokines relate to distinct allergic phenotypes. The relevance of Th1/Th2 and regulatory cytokines to development of new allergen-specific therapies is also discussed.