Reduced transforming growth factor‐β1‐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 maternallyingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-g 1 (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 clinicopathological 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-g 1 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-g 1 + lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-g 1 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.

Cow's milk–specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

“…26 Recently, it has been described that the amount of TGF-b-producing T cells in the duodenal mucosa was decreased in children with food allergy. 27 Therefore one might speculate that the observed reduced production of TGF-b in food allergy might lead to insufficient induction of tolerance, resulting in reduced production of IL-10 in children with CMA, as shown in our study.…”

The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

“…Since the oral antigen is taken up through the intestine, the gut-associated lymphoid tissue (GALT) seems to be involved with the induction of oral tolerance. 29) It has been reported that TCRgd-T cells produce the regulatory cytokine transforming growth factor-b1 (TGF-b1) in vitro and induce oral tolerance in vivo, 30) suggesting that the TCRgd-T cells among the IELs produce the regulatory cytokines (TGF-b1 and/or IL-10) upon stimulation and function as regulatory T cells which inhibit antigen-specific T cells. 31) In conclusion, the decrease in the number of gd-IELs caused by anti-TCRgd antibody treatment increased oral sensitization of wild-type (ϩ/ϩ) mice.…”

Immune responses in dogs with cutaneous adverse food reactions

“…In cow's milk allergic humans with intestinal signs, the intestinal lymphocytes showed a Th2 cytokine profile (Beyer et al 2002). In addition, decreased TGF-1 expression was seen in duodenal epithelial and laminia propria lymphocytes in children with multiple food allergies (Pe´rez-Machado et al 2003), suggesting a switch from a Th1 to a Th2 environment and/or a failure in oral tolerance with allergy as the outcome. In contrast, no change in T-cell phenotypes or a distinct Th1, Th2, or Treg profile was detected in the duodenum of dogs with only cutaneous clinical signs of food hypersensitivity, suggesting that the intestinal mucosa is not the primary site of T-cell activation that eventually leads to cutaneous food hypersensitivity (Veenhof et al 2010).…”