The kinetics of change in cytokine production by CD4 + T cells during conventional allergen immunotherapy

Abstract

Background: The effect of conventional allergen immunotherapy on allergen-specific T lymphocyte cytokine production is incompletely understood, particularly during the initial phase of treatment. Objective: The purpose of this study was to prospectively follow the kinetics of change in CD4 + T cell cytokine secretion during the course of conventional immunotherapy. Methods: Six allergic individuals were treated with extracts of Dermatophagoides farinae/Dermatophagoides pteronyssinus or with rye grass pollen (Lolium perenne) allergen, but not both, by using an internally controlled conventional immunotherapy protocol. CD4 + T cells from peripheral blood were examined in vitro at varying intervals after the initiation of immunotherapy by stimulation with D farinae or L perenne group I antigen. The quantity of IL-4 and IFN-γ produced and its relationship to clinical improvement was determined. Results: The ratio of allergen-specific IL-4/IFN-γ production by CD4 + T cells from 4 of 6 individuals receiving immunotherapy greatly increased during the period when the dose of allergen was increasing. However, after high-dose maintenance therapy was achieved, this ratio decreased in subjects responding clinically to, but not in those failing, immunotherapy. In addition, late-phase skin reactions and allergen-specific IgE levels in responding, but not in nonresponding, subjects diminished over the course of immunotherapy. Conclusion: Conventional immunotherapy may initially exacerbate allergic disease by increasing allergen-specific IL-4 and allergen-specific IgE production. Later clinical improvement is associated with a reduction in allergen-specific IL-4 production and in allergen-specific serum IgE. (J Allergy Clin Immunol 1999;103:468-75.)