Tolerance to ingested deamidated gliadin in mice is maintained by splenic, type 1 regulatory T cells

Gastroenterology. 2011 Aug;141(2):610-20, 620.e1-2. doi: 10.1053/j.gastro.2011.04.048. Epub 2011 Apr 28.


Background & aims: Patients with celiac disease have permanent intolerance to gluten. Because of the high frequency of this disorder (approximately 1 in 100 individuals), we investigated whether oral tolerance to gluten differs from that to other food proteins.

Methods: Using transgenic mice that express human HLA-DQ2 and a gliadin-specific, humanized T-cell receptor, we compared gluten-specific T-cell responses with tolerogenic mucosal T-cell responses to the model food protein ovalbumin.

Results: Consistent with previous findings, the ovalbumin-specific response occurred in the mesenteric lymph nodes and induced Foxp3(+) regulatory T cells. In contrast, ingestion of deamidated gliadin induced T-cell proliferation predominantly in the spleen but little in mesenteric lymph nodes. The gliadin-reactive T cells had an effector-like phenotype and secreted large amounts of interferon gamma but also secreted interleukin-10. Despite their effector-like phenotype, gliadin-reactive T cells had regulatory functions, because transfer of the cells suppressed a gliadin-induced, delayed-type hypersensitivity response.

Conclusions: Ingestion of deamidated gliadin induces differentiation of tolerogenic, type 1 regulatory T cells in spleens of HLA-DQ2 transgenic mice. These data indicate that under homeostatic conditions, the T-cell response to deamidated gliadin is tolerance, which is not conditioned by the mucosal immune system but instead requires interleukin-10 induction by antigen presentation in the spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism
  • Forkhead Transcription Factors / immunology
  • Gliadin / immunology*
  • Gliadin / pharmacology
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • HLA-DQ Antigens / metabolism
  • Immune Tolerance / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-12 / metabolism
  • Lymph Nodes / immunology
  • Mesentery
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Spleen / drug effects
  • Spleen / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • HLA-DQ Antigens
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • Ovalbumin
  • Gliadin