23118 Effector T Cells' Resistance to Regulatory T Cells Offers Clue to Loss of Gluten Tolerance and Autoimmunity in Celiac Disease - Celiac.com
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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.

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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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George, i am sorry that you are not feeling well! ?? I am not a doctor, but just trying out drugs to stop your symptoms just seems like a band aid approach. It sounds like he suspects IBS which is really, in my opinion, "I be stumped". Has inflammatory bowel disorder (IBD) (more lovely autoimmune disorders) been ruled out? This includes both Crohn's and Colitis. My niece was diagnosed with Crohn's finally with a pill camera after all other tests were given. The damage was not within reach of any scope. I am just throwing out suggestions. Hopefully, you and your doctor will figure it out soon!

Celiac disease is an autoimmune disease that happens to have a known trigger -- gluten. Flare-ups develop (antibodies) causing damage. Not just in the small intestine, but systemically. One gluten exposure can cause antibodies to increase for days or months! Antibodies are being measured during the celiac blood tests. If there is no gluten exposure, there will be no antibodies. These antibodies can come down in some people in as little as two weeks. Recommendations require gluten 2 to 4 weeks daily for the biopsies taken via endoscopy in order to be sure to catch damage, but 8 to 12 weeks for the blood tests. The endoscopy is considered the "gold standard" in helping to diagnose celiac disease, but there are other things that can damage the small intestine. So, the blood test helps solidify the diagnosis. So, if you want a good result on your endoscopy, you need to be eating gluten daily for two week prior at a minimum. I know it is tough and you are feeling sick. Wish there was a better way to catch active celiac disease.

Hi everyone, Just an update to my situation. I had thought that I might be getting better since I started adding gluten-free grain back into my diet but I was wrong. It seems that the Methscopalamine Bromide just delayed the effects, didn't stop them. I had to stop taking it because one of the side effects is to stop sweating, which I did. There were times when I felt hot and almost couldn't catch my breath. Anyway, my doc put me on Viberzi instead. I took 3 doses, 1 Tuesday evening and then 1 Wednesday morning and then again Wednesday evening. Each time I took 1, it seemed that about half an hour later I would develop severe abdominal cramping, pain in my neck, shoulders and upper back and a feeling like my insides were on fire. My face felt like it was hot and tingling. It wasn't warm to the touch but felt like it to me. Worse of all is it didn't work anyway, I still had diarrhea. I stopped taking Viberzi after reading the precautions pamphlet which said, "stop taking Viberzi and tell your doctor if you have abdominal cramping, pain which radiates to your shoulders or upper back." Go figure. Anyway, today is 3 weeks straight of diarrhea and still no diagnosis and not sure what he's going to want to do next. George

I'm still really new to all this but is it common to have trouble with sleep? I swear since my symptoms got really bad a few months ago I can't get 1 good nights sleep, like a 5 hour stretch is doing real good. Wake up at 3am wide awake almost every night. Told my doctor and they've recommended melatonin, that doesn't work. Tried chamomile and lavender tea, no help. Tried zzquil, that will knock me out but maybe for like an extra hour then I'm really drowsy the next morning from it. I don't know what to do.

I have 2 copies of DQ9. One from each parent.