Impaired control of effector T cells by regulatory T cells: A clue to loss of oral tolerance and autoimmunity in celiac disease?

American Journal of Gastroenterology

Volumn 107, Issue 4, 2012, Pages 604-611

  Hmida, Nadia Belhadj ^a,b   Ahmed, Mélika Ben ^a,b   Moussa, Amel ^b,c   Rejeb, Majd Ben ^c   Said, Yosra ^b,c   Kourda, Nadia ^b,c   Meresse, Bertrand ^d,e   Abdeladhim, Maha ^a,b   Louzir, Hechmi ^a,b   Cerf Bensussan, Nadine ^d,e  

^a PASTEUR INSTITUTE OF TUNIS   (Tunisia)

^b UNIVERSITY OF TUNIS EL MANAR   (Tunisia)

^c CHARLES NICOLLE HOSPITAL   (Tunisia)

^d INSERM   (France)

^e UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; GLUTEN; INTERLEUKIN 15; MESSENGER RNA; TRANSCRIPTION FACTOR FOXP3;

ADULT; ARTICLE; AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CELIAC DISEASE; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE ACTIVITY; DISEASE DURATION; DOWN REGULATION; EFFECTOR CELL; HUMAN; HUMAN TISSUE; IN VITRO STUDY; INTERFERON PRODUCTION; LAMINA PROPRIA; LYMPHOCYTE PROLIFERATION; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION;

ADULT; AUTOIMMUNITY; BIOPSY; CASE-CONTROL STUDIES; CD4-POSITIVE T-LYMPHOCYTES; CELIAC DISEASE; DUODENUM; FEMALE; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNE TOLERANCE; INTERFERON-GAMMA; INTERLEUKIN-15; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTESTINAL MUCOSA; MALE; MIDDLE AGED; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; STATISTICS, NONPARAMETRIC; T-LYMPHOCYTES, REGULATORY;

EID: 84859571744     PISSN: 00029270     EISSN: 15720241     Source Type: Journal    
DOI: 10.1038/ajg.2011.397     Document Type: Article

References (35)

1. Qiao SW, Sollid LM, Blumberg RS. Antigen presentation in celiac disease. Curr Opin Immunol 2009;21:111-7.
2. Black KE, Murray JA, David CS. HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. J Immunol 2002;169:5595-600. (Pubitemid 35291659)
3. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005;6:345-52. (Pubitemid 41716771)
4. Bennett CL, Christie J, Ramsdell F et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27:20-1. (Pubitemid 32044513)
5. Gambineri E, Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003;15:430-5. (Pubitemid 36774255)
6. Torgerson TR, Linane A, Moes N et al. Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology 2007;132:1705-17. (Pubitemid 46695720)
7. Tsuji NM, Kosaka A. Oral tolerance: intestinal homeostasis and antigen-specific regulatory T cells. Trends Immunol 2008;29:532-40.
8. Hadis U, Wahl B, Schulz O et al. Intestinal tolerance requires gut homing and expansion of FoxP3(+) regulatory T cells in the lamina propria. Immunity 2011;34:237-46.
9. Bjornvold M, Amundsen SS, Stene LC et al. FOXP3 polymorphisms in type 1 diabetes and coeliac disease. J Autoimmun 2006;27:140-4. (Pubitemid 44529716)
10. Frisullo G, Nociti V, Iorio R et al. Increased CD4+CD25+Foxp3+ T cells in peripheral blood of celiac disease patients: correlation with dietary treatment. Hum Immunol 2009;70:430-5.
11. Granzotto M, dal Bo S, Quaglia S et al. Regulatory T-cell function is impaired in celiac disease. Dig Dis Sci 2009;54:1513-9.
12. Tiittanen M, Westerholm-Ormio M, Verkasalo M et al. Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. Clin Exp Immunol 2008;152:498-507. (Pubitemid 351661513)
13. Vorobjova T, Uibo O, Heilman K et al. Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease and type I diabetes mellitus. Scand J Gastroenterol 2009;44:422-30.
14. Brazowski E, Cohen S, Yaron A et al. FOXP3 expression in duodenal mucosa in pediatric patients with celiac disease. Pathobiology 2010;77:328-34.
15. Westerholm-Ormio M, Vaarala O, Tiittanen M et al. Infiltration of Foxp3- and Toll-like receptor-4-positive cells in the intestines of children with food allergy. J Pediatr Gastroenterol Nutr 2010;50:367-76.
16. Mention JJ, Ben Ahmed M, Begue B et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 2003;125:730-45. (Pubitemid 37070691)
17. Di Sabatino A, Ciccocioppo R, Cupelli F et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 2006;55:469-77.
18. Ben Ahmed M, Sellami H, Belhadj Hmida N et al. Increased serum level of IL-15 in celiac disease: a role in the loss of peripheral immune homeostasis? Gastroenterology 2009;136 (Suppl 1):A-428.
19. DePaolo RW, Abadie V, Tang F et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 2011;471:220-4.
20. Ben Ahmed M, Belhadj Hmida N, Moes N et al. IL-15 renders conventional lymphocytes resistant to suppressive functions of regulatory T cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol 2009;182:6763-70.
21. Cerf-Bensussan N, Guy-Grand D, Griscelli C. Intraepithelial lymphocytes of human gut: isolation, characterisation and study of natural killer activity. Gut 1985;26:81-8. (Pubitemid 15109207)
22. Cellier C, Delabesse E, Helmer C et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet 2000;356:203-8. (Pubitemid 30446975)
23. Zanzi D, Stefanile R, Santagata S et al. IL-15 interferes with suppressive activity of intestinal regulatory T cells expanded in celiac disease. Am J Gastroenterol 2011;106:1308-17.
24. Sarnacki S, Begue B, Buc H et al. Enhancement of CD3-induced activation of human intestinal intraepithelial lymphocytes by stimulation of the beta 7-containing integrin defined by HML-1 monoclonal antibody. Eur J Immunol 1992;22:2887-92.
25. Ebert EC. Inhibitory effects of transforming growth factor-beta (TGF-beta) on certain functions of intraepithelial lymphocytes. Clin Exp Immunol 1999;115:415-20. (Pubitemid 29130354)
26. Peluso I, Fantini MC, Fina D et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J Immunol 2007;178:732-9. (Pubitemid 46095145)
27. Karakhanova S, Munder M, Schneider M e t al. Highly efficient expansion of human CD4+CD25+ regulatory T cells for cellular immunotherapy in patients with graft-versus-host disease. J Immunother 2006;29:336-49. (Pubitemid 44297302)
28. McClymont SA, Putnam AL, Lee MR et al. Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J Immunol 2011;186:3918-26.
29. Benahmed M, Meresse B, Arnulf B et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 2007;132:994-1008. (Pubitemid 46440858)
30. Meresse B, Ripoche J, Heyman M et al. Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol 2009;2:8-23.
31. Viljamaa M, Kaukinen K, Huhtala H et al. Coeliac disease, autoimmune diseases and gluten exposure. Scand J Gastroenterol 2005;40:437-43. (Pubitemid 40546911)
32. Cosnes J, Cellier C, Viola S et al. Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet. Clin Gastroenterol Hepatol 2008;6:753-8.
33. Olaussen RW, Karlsson MR, Lundin KE et al. Reduced chemokine receptor 9 on intraepithelial lymphocytes in celiac disease suggests persistent epithelial activation. Gastroenterology 2007;132:2371-82. (Pubitemid 46890871)
34. Malamut G, El Machhour R, Montcuquet N et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. J Clin Invest 2010;120:2131-43.
35. Fehniger TA, Suzuki K, Ponnappan A et al. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J Exp Med 2001;193:219-31. (Pubitemid 32524453)