Effector T Cells' Resistance to Regulatory T Cells Offers Clue to Loss of Gluten Tolerance and Autoimmunity in Celiac Disease

Celiac.com 12/05/2012 - Regulatory T cells (Tregs) are play a pivotal role in helping our bodies tolerate self-antigens and dietary proteins. Interleukin (IL)-15 is a cytokine that is overly present in the intestines of patients with celiac disease.

Studies have shown that Interleukin (IL)-15 does not interfere with the generation of functional Tregs, but causes human T cells to resist Treg suppression.

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To better understand how control of effector T cells by regulatory T cells is inhibited, a team of researchers compared Treg numbers and responses of intestinal and peripheral T lymphocytes to suppression by Tregs in celiac disease patients and in a control group.

The research team included N.B. Hmida, M. Ben Ahmed, A. Moussa, M.B. Rejeb, Y. Said, N. Kourda, B. Meresse, M. Abdeladhim, H. Louzir, and N. Cerf-Bensussan. They are affiliated with the Department of Clinical Immunology and the Institut Pasteur de Tunis in Tunis, Tunisia.

For their study, the team isolated intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) from duodenal biopsy specimens of patients with celiac disease and in a control group.

The team then purified CD4+CD25+ T lymphocytes (Tregs) from blood. By analyzing anti-CD3-induced proliferation and interferon (IFN)-γ production in the presence or absence of peripheral Tregs, they were able to test responses of IELs, of LPLs, and peripheral lymphocytes (PBLs) to suppression by Tregs. The team used flow cytometry to measure lamina propria and peripheral CD4+CD25+FOXP3+ T cells.

They found that, although patients with active celiac disease showed significantly increased percentages of CD4+CD25+FOXP3+ LPLs, they also showed less inhibited proliferation and IFN-γ production of intestinal T lymphocytes by autologous or heterologous Tregs (P < 0.01). IEL for subjects with celiac disease showed no response to Tregs.

Also, the team noted resistance of LPLs and PBLs to Treg suppression in patients with villous atrophy who had substantially higher blood levels of IL-15 compared with patients without villous atrophy and controls.

From their results, the research team concludes that effector T lymphocytes in people with active celiac disease become resistant to suppression by Tregs.

This resistance may result in loss of tolerance to gluten, and to self-antigens.

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