Reduced transforming growth factor-beta1-producing T cells in the duodenal mucosa of children with food allergy

Abstract

Infant food allergies are increasing, and many breast-fed infants now sensitize to maternally-ingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-beta1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinico-pathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF-beta1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF-beta1(+) lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-beta1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.