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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Man
Angela L
AL
Laboratory of Gut Immunology, Programme of Gastrointestinal Health and Function, Institute of Food Research, Colney, Norwich NR4 7UA, UK.
Bertelli
Eugenio
E
Regoli
Mari
M
Chambers
Stephen J
SJ
Nicoletti
Claudio
C
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002417:Cattle; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D019014:fas Receptor