IgE-Dependent Activation of T cells by Allergen in Atopic Dermatitis: Pathophysiologic Relevance

Abstract

The importance of interactions between allergen and IgE in allergen-mediated activation of T lymphocytes from patients with atopic dermatitis (AD) is unclear. A role for this interaction is implied by past evidence for IgE-facilitated presentation of allergen to T cells, but this phenomenon has only been demonstrated in specific in vitro systems biased to maximize the effect. It is therefore not known whether the process is relevant in patients. We now show that the responses to allergen of unmodified peripheral blood mononuclear cells (PBMC) from individual AD patients are significantly greater in the presence of fresh, unheated, IgE-containing autologous serum than the same serum heated under IgE-denaturing conditions or specifically depleted of IgE by immunoprecipitation. In six independent experiments, 59%-67% of the maximal in vitro PBMC response to allergen was found to be dependent upon the presence of IgE in autologous serum used at 5% final concentration. These data provide the first evidence that sufficient amounts of allergen-specific IgE and allergen-reactive T cells occur concomitantly in the blood of individual AD patients to allow IgE-enhanced T cell responses to allergen. We conclude that IgE-enhanced T cell responses are pathophysiologically relevant and a therapeutic target in AD.