Reduced transforming growth factor-β1-producing T cells in the duodenal mucosa of children with food allergy

Miguel A. Pérez-Machado, Paul Ashwood, Michael A. Thomson, Frances Latcham, Rosalind Sim, John A. Walker-Smith, Simon H. Murch

Research output: Contribution to journalArticle

116 Citations (Scopus)

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-β1 (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-β1 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-β1+ lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-β1 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.

Original languageEnglish (US)
Pages (from-to)2307-2315
Number of pages9
JournalEuropean Journal of Immunology
Volume33
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Food Hypersensitivity
Transforming Growth Factors
Mucous Membrane
T-Lymphocytes
Lymphocytes
Regulatory T-Lymphocytes
In Situ Hybridization
Immunohistochemistry
Infant Food
Biopsy
Celiac Disease
Enterobacteriaceae
Innate Immunity
Abdomen
Endoscopy
Flow Cytometry
Breast
Epithelium
Cytokines
Antigens

Keywords

  • Celiac disease
  • Food allergy
  • Lymphocytes
  • TGF-β

ASJC Scopus subject areas

  • Immunology

Cite this

Pérez-Machado, M. A., Ashwood, P., Thomson, M. A., Latcham, F., Sim, R., Walker-Smith, J. A., & Murch, S. H. (2003). Reduced transforming growth factor-β1-producing T cells in the duodenal mucosa of children with food allergy. European Journal of Immunology, 33(8), 2307-2315. https://doi.org/10.1002/eji.200323308

Reduced transforming growth factor-β1-producing T cells in the duodenal mucosa of children with food allergy. / Pérez-Machado, Miguel A.; Ashwood, Paul; Thomson, Michael A.; Latcham, Frances; Sim, Rosalind; Walker-Smith, John A.; Murch, Simon H.

In: European Journal of Immunology, Vol. 33, No. 8, 01.08.2003, p. 2307-2315.

Research output: Contribution to journalArticle

Pérez-Machado, Miguel A. ; Ashwood, Paul ; Thomson, Michael A. ; Latcham, Frances ; Sim, Rosalind ; Walker-Smith, John A. ; Murch, Simon H. / Reduced transforming growth factor-β1-producing T cells in the duodenal mucosa of children with food allergy. In: European Journal of Immunology. 2003 ; Vol. 33, No. 8. pp. 2307-2315.
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