T Cell Responses to Food Protein in Acute Food Protein-Induced Enterocolitis (FPIES)


      FPIES is a non-IgE-mediated gastrointestinal food allergy with poorly characterized pathophysiology. We sought to characterize T cell responses in acute FPIES.


      Whole blood samples were collected from 8 children with FPIES to milk, confirmed by a standardized oral food challenge; 18 children with IgE-mediated milk allergy and 7 milk-tolerant children were included as controls. Peripheral blood mononuclear cells (PBMCs) were stained with CFSE and stimulated with endotoxin-free caseins, anti-CD3/CD28 beads (positive control) and medium (negative control) for 7 days in the presence of IL-2, followed by staining with fluorescent markers and flow-cytometric analysis. Following 48 hour-incubation, supernatants were collected and cytokines were quantified by a multiplex immunoassay (FlowCytomix Multiplex kit, eBioscience).


      Median age of milk-FPIES subjects was 8.4 years (2.2 to 18.8), IgE-mediated milk-allergic subjects was 7.6 years (4.6 to 10.7), and milk-tolerant subjects was 5.9 years (4.6 to 10.9); P = 0.55. Proliferating casein-specific T effector cells frequency (CFSElowCD3+CD4+) was similar in all groups, i.e. 29.9% (23.1 to 44.4) in milk-FPIES, 21.5% (4.5 to 50.9) in IgE-mediated milk allergy and 29.7% (18.9 to 58.8) in milk-tolerant controls. After antigen-specific stimulation, there were no differences among the groups in secretion of TH2 cytokines (IL-5, IL-6 and IL-13) as well as IFN-γ and TNF-α However, we observed a significantly lower secretion of IL-10 in FPIES patients, compared to patients with IgE-mediated allergy and outgrown patients.


      A TH2 activation may contribute to the pathophysiology of FPIES and T cell-derived IL-10 may play a role in the acquisition of immunotolerance.