Antigen-specific T cell-mediated apoptosis of dendritic cells is impaired in a mouse model of food allergy.

Abstract

Dendritic cells (DCs) play a pivotal role in antigen presentation and regulation of immune responses, and strong evidence suggests their involvement in the pathogenesis of allergy. However, hitherto, DC-T-cell cross-talk in relation to IgE-mediated allergic reactions to food has not been investigated. Our aim was to investigate T cell-mediated apoptosis of myeloid DCs from spleen and Peyer's patches of mice with cow's milk (CM) allergy after cognate interaction with antigen (CM)-specific T cells. Freshly isolated myeloid CD11c(+/hi)/B220(-) DCs from spleen and Peyer's patches of mice with CM allergy and control mice were cultured with CM-specific T cells in the presence or absence of CM or unrelated antigen as a control. Levels of apoptosis in DCs were evaluated by assessing propidium iodide uptake and annexin V expression by means of flow cytometry. We observed that both systemic and gastrointestinal-derived DCs showed an increased resistance to T cell-mediated cell death compared with DCs from control but not allergic donors. Further experiments demonstrated that in both allergic and control mice, T cell-mediated DC apoptosis takes place exclusively in the presence of the specific antigen, is MHC II dependent, and is only partially CD95-CD95 ligand dependent. Here we demonstrate, for the first time, that the reciprocal, finely balanced regulation between these 2 cell types, which plays a central role in controlling immune responses, is altered in allergy. We hypothesize that these events are likely to have a profound influence on the genesis and maintenance of adverse reaction to food.