Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-gamma

The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE antibody responses in a significant proportion of patients suffering f rom dust mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell surface molecule involved in the homeostatic control of huma n IgE synthesis, namely the IL-2 receptor (Ca25) on T cells. As a result, t hese T cells show markedly diminished proliferation and IFN-gamma secretion in response to stimulation by anti-CDS antibody. However, these observatio ns still leave open the important issue of whether CD25 cleavage, and the c onsequent suppression of IFN-gamma secretion, leads to enhanced IL-4 secret ion, and whether such cytokine changes would be exhibited by both CD4 and C D8 T cells. Here we demonstrate for the first time that the proteolytic act ivity of Der p 1 biases human CD4 and CD8 T cells towards a type 2 cytokine profile. Our data provide compelling evidence for the role of the proteoly tic activity of Der p 1 in creating a microenvironment conducive for IgE sy nthesis.