T cell receptor-V beta repertoire in allergen-specific sensitization and increased airway responsiveness

Abstract

An animal model system was developed to study the mechanisms resulting in allergic sensitization. Local allergen exposure via the airways and the lung stimulated an allergen-specific immunoglobulin E (IgE) response that was paralleled by the development of increased airway responsiveness (AR). It was found that CD4+ T cells of local draining lymph nodes played an important role in the regulation of these events. Stimulation of allergen-specific T cells requires interaction between major histocompatibility complex (MHC) class II molecules (expressed on antigen-presenting cells), peptide (presented on MHC) and the T cell receptor. Allergen sensitization stimulated T cells that expressed a restricted T cell receptor V beta (TCR-V beta) elements. Each allergen stimulated different V beta elements, and sensitization to the same allergen resulted in a different pattern of TCR-V beta stimulation in different lymphoid tissues. Some of these T cells had pro-allergenic effects, whereas others were able to inhibit the development of the allergic response, including the development of increased AR. These data indicate that the local T cell response regulates the type of immune response that evolves following local allergen sensitization.