IgE-associated enhancement of allergen presentation and T cell activation in atopic dermatitis

Previous research has suggested that IgE-facilitated allergen presentation may play a key role in the pathogenesis of atopic dermatitis. This is the process by which allergen-specific IgE bound to Fcepsilon receptors on antigen presenting cells is able to enhance the uptake and presentation of allergen and thus the activation of allergen-specific T cells. However, until now IgE-facilitated allergen presentation has only been demonstrated in systems biased to maximise this process. This present work sought to determine whether IgE-mediated enhancement of allergen presentation could be demonstrated in vitro using human peripheral blood mononuclear cells from atopic dermatitis donors cultured in the presence of 10% autologous serum containing allergen-specific IgE. PBMC from 11/20 atopic dermatitis patients responded in a dose-dependent manner to Der p with maximal stimulation index (mSI) values of 3.7-70.7, whereas normal donors did not respond (mSI < 2.7, n=8). Heating of autologous serum at 56°C for 60 minutes, conditions which irreversibly denature IgE, caused major reductions in peripheral blood mononuclear cell responses to Der p (p=0.002, paired t test, n=9). Incubation of peripheral blood mononuclear cells with blocking monoclonal antibodies against the high (FcepsilonRI) and low (CD23) affinity IgE receptors produced inconsistent inhibition of responses to in vitro (n=6). Flow cytometric measurements on peripheral blood leucocytes from AD patients further indicated that IgE-receptor blocking antibodies were unable to displace monocyte surface bound IgE, even after 24 hours in culture. However, peripheral blood mononuclear cell responses to Der p were significantly reduced in cultures containing 5% IgE depleted serum compared to unmodified serum (mean mSI 8.8 and 20.6 respectively, p