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  • Jefferson Adams
    Jefferson Adams

    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.

    Photo: CC--J_Arrr!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.

    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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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

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    Celiac.com 05/31/2005 – Researchers in the United States have found that introducing gluten too early or too late in an infants diet may play a key role in whether or not they eventually develop celiac disease autoimmunity. From 1994 to 2004 the researchers followed 1,560 high-risk children (those with either HLA-DR3 or DR4 alleles, or with a first-degree relative with type 1 diabetes) who were periodically screened for celiac disease autoimmunity. Positive results were defined by two positive tissue transglutaminase (tTG) blood serum tests, or one positive tTG and a positive small bowel biopsy. The researchers conducted a prospective observational study in which the parents of the children in the study responded to a questionnaire regarding the timing of gluten introduction into their childrens diets. To avoid a bias on the answers the researchers purposely did not include children who already had celiac disease. During the mean duration period of the study (4.8 years), 51 children developed celiac disease autoimmunity. Their findings indicate that children who were first introduced to gluten when they were less than 3 months of age had a five-fold increased risk of developing celiac disease autoimmunity when compared to children who were first introduced to gluten at 4-6 months old. Additionally, those who were first introduced at 7 months or older had a marginally increased risk of getting celiac disease autoimmunity when compared with the same group.
    Based on these findings the researchers recommend that parents should introduce cereals into their childrens diets at 4-6 months of age—even though this conflicts with recent recommendations by the American Academy of Pediatrics, who recommend breast-feeding only until 6 months of age. The researchers stress that much larger international prospective studies need be done in this area to answer the many questions that this study raises.

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