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

Du Pré, M; Kozijn, A; van Berkel, L; ter Borg, M; Lindenbergh-Kortleve, D; Jensen, LT; Kooy-Winkelaar, Y; Koning, F; Boon, L; Nieuwenhuis, E; Sollid, L; Fugger, L; Samsom, J

Journal article

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

Abstract:: BACKGROUND and 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 status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Du Pré, M., Kozijn, A., van Berkel, L., ter Borg, M., Lindenbergh-Kortleve, D., Jensen, L. T., Kooy-Winkelaar, Y., Koning, F., Boon, L., Nieuwenhuis, E., Sollid, L., Fugger, L., & Samsom, J. (2011). Tolerance to ingested deamidated gliadin in mice is maintained by splenic, type 1 regulatory T cells. Gastroenterology, 141(2), 610–620.e2.

MLA Style

Du Pré, M, et al. “Tolerance to Ingested Deamidated Gliadin in Mice Is Maintained by Splenic, Type 1 Regulatory T Cells.” Gastroenterology, vol. 141, no. 2, 2011, pp. 610–20.e2.

Chicago Style

Du Pré, M, A Kozijn, L van Berkel, et al. 2011. “Tolerance to Ingested Deamidated Gliadin in Mice Is Maintained by Splenic, Type 1 Regulatory T Cells.” Gastroenterology 141 (2): 610–20.e2.
Print