Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice

Journal of Immunology

Volumn 187, Issue 8, 2011, Pages 4338-4346

  Galipeau, Heather J ^a   Rulli, Nestor E ^b   Jury, Jennifer ^a   Huang, Xianxi ^a   Araya, Romina ^b   Murray, Joseph A ^c,d   David, Chella S ^d   Chirdo, Fernando G ^b   McCoy, Kathy D ^a,e   Verdu, Elena F ^a  

^a MCMASTER UNIVERSITY MEDICAL CENTRE   (Canada)

^b UNIVERSIDAD NACIONAL DE LA PLATA   (Argentina)

^c Mayo Clinic College of Medicine   (United States)

^d MAYO GRADUATE SCHOOL   (United States)

^e UNIVERSITY OF BERN   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BASILIXIMAB; CYTOKINE; GLIADIN; TRANSCRIPTION FACTOR FOXP3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL ISOLATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE COURSE; DISEASE SEVERITY; DQ8 GENE; ENTEROPATHY; GENE; INSULITIS; LYMPH NODE; LYMPHOCYTOSIS; MALE; MOUSE; MUCOSAL DISEASE; NONHUMAN; NONOBESE DIABETIC MOUSE; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN INTAKE; PROTEIN INTOLERANCE; SENSITIZATION; T LYMPHOCYTE;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELL SEPARATION; DIABETES MELLITUS, EXPERIMENTAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GLIADIN; HLA-DQ ANTIGENS; HUMANS; IMMUNOHISTOCHEMISTRY; INTESTINAL DISEASES; MALE; MICE; MICE, INBRED NOD; MICE, TRANSGENIC; PANCREATITIS;

EID: 80054738919     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1100854     Document Type: Article

References (88)

1. Green, P. H. R., and B. Jabri. 2003. Coeliac disease. Lancet 362: 383-391. (Pubitemid 36945070)
2. Fasano, A., I. Berti, T. Gerarduzzi, T. Not, R. B. Colletti, S. Drago, Y. Elitsur, P. H. Green, S. Guandalini, I. D. Hill, et al. 2003. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch. Intern. Med. 163: 286-292. (Pubitemid 36183856)
3. Not, T., K. Horvath, I. D. Hill, J. Partanen, A. Hammed, G. Magazzu, and A. Fasano. 1998. Celiac disease risk in the USA: high prevalence of anti-endomysium antibodies in healthy blood donors. Scand. J. Gastroenterol. 33: 494-498. (Pubitemid 28277248)
4. Schuppan, D., Y. Junker, and D. Barisani. 2009. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 137: 1912-1933.
5. Kagnoff, M. F. 2007. Celiac disease: pathogenesis of a model immunogenetic disease. J. Clin. Invest. 117: 41-49. (Pubitemid 46048448)
6. Rubio-Tapia, A., R. A. Kyle, E. L. Kaplan, D. R. Johnson, W. Page, F. Erdtmann, T. L. Brantner, W. R. Kim, T. K. Phelps, B. D. Lahr, et al. 2009. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology 137: 88-93.
7. Lambert, A. P., K. M. Gillespie, G. Thomson, H. J. Cordell, J. A. Todd, E. A. M. Gale, and P. J. Bingley. 2004. Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: a population-based study in the United Kingdom. J. Clin. Endocrinol. Metab. 89: 4037-4043. (Pubitemid 39089121)
8. Daneman, D. 2006. Type 1 diabetes. Lancet 367: 847-858. (Pubitemid 43363372)
9. Borchers, A. T., R. Uibo, and M. E. Gershwin. 2010. The geoepidemiology of type 1 diabetes. Autoimmun. Rev. 9: A355-A365.
10. Larsson, K., A. Carlsson, E. Cederwall, B. Jönsson, J. Neiderud, B. Jonsson, Å. Lernmark, and S. A. Ivarsson; Skåne Study Group. 2008. Annual screening detects celiac disease in children with type 1 diabetes. Pediatr. Diabetes 9: 354-359.
11. Güvenç, S., S. Kaymakoǧlu, N. Gürel, K. Karşidaǧ, K. Demir, D. Dinçer, C. Kekik, S. Salman, T. Yilmaz, F. Beşişik, and Y. Cakaloǧlu. 2002. The prevalence of manifest and latent celiac disease in type 1 diabetes mellitus. Turk. J. Gastroenterol. 13: 103-107. (Pubitemid 34764758)
12. Spiekerkoetter, U., J. Seissler, and U. Wendel. 2002. General screening for celiac disease is advisable in children with type 1 diabetes. Horm. Metab. Res. 34: 192-195. (Pubitemid 34553532)
13. Collin, P., J. Salmi, O. Hällström, H. Oksa, H. Oksala, M. Mäki, and T. Reunala. 1989. High frequency of coeliac disease in adult patients with type-I diabetes. Scand. J. Gastroenterol. 24: 81-84. (Pubitemid 19071843)
14. Mahmud, F. H., J. A. Murray, Y. C. Kudva, A. R. Zinsmeister, R. A. Dierkhising, B. D. Lahr, P. J. Dyck, R. A. Kyle, M. El-Youssef, and L. J. Burgart. 2005. Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features. Mayo Clin. Proc. 80: 1429-1434. (Pubitemid 41567220)
15. Dieterich, W., T. Ehnis, M. Bauer, P. Donner, U. Volta, E. O. Riecken, and D. Schuppan. 1997. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat. Med. 3: 797-801. (Pubitemid 27298728)
16. Doolan, A., K. Donaghue, J. Fairchild, M. Wong, and A. J. Williams. 2005. Use of HLA typing in diagnosing celiac disease in patients with type 1 diabetes. Diabetes Care 28: 806-809. (Pubitemid 40434477)
17. Saukkonen, T., J. Ilonen, H. K. Åkerblom, and E. Savilahti. 2001. Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1*02 allele. Diabetologia 44: 1051-1053. (Pubitemid 32778139)
18. Shanahan, F., R. McKenna, C. F. McCarthy, and M. I. Drury. 1982. Coeliac disease and diabetes mellitus: a study of 24 patients with HLA typing. Q. J. Med. 51: 329-335. (Pubitemid 13111031)
19. Harrison, L. C., and M. C. Honeyman. 1999. Cow's milk and type 1 diabetes: the real debate is about mucosal immune function. Diabetes 48: 1501-1507. (Pubitemid 29356855)
20. Mojibian, M., H. Chakir, D. E. Lefebvre, J. A. Crookshank, B. Sonier, E. Keely, and F. W. Scott. 2009. Diabetes-specific HLA-DR-restricted proinflammatory T-cell response to wheat polypeptides in tissue transglutaminase antibody-negative patients with type 1 diabetes. Diabetes 58: 1789-1796.
21. Norris, J. M., K. Barriga, E. J. Hoffenberg, I. Taki, D. Miao, J. E. Haas, L. M. Emery, R. J. Sokol, H. A. Erlich, G. S. Eisenbarth, and M. Rewers. 2005. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA 293: 2343-2351. (Pubitemid 40676756)
22. Norris, J. M., K. Barriga, G. Klingensmith, M. Hoffman, G. S. Eisenbarth, H. A. Erlich, and M. Rewers. 2003. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290: 1713-1720. (Pubitemid 37430621)
23. Smyth, D. J., V. Plagnol, N. M. Walker, J. D. Cooper, K. Downes, J. H. Yang, J. M. Howson, H. Stevens, R. McManus, C. Wijmenga, et al. 2008. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N. Engl. J. Med. 359: 2767-2777.
24. Plenge, R. M. 2008. Shared genetic risk factors for type 1 diabetes and celiac disease. N. Engl. J. Med. 359: 2837-2838.
25. Mackay, I. R. 2009. Clustering and commonalities among autoimmune diseases. J. Autoimmun. 33: 170-177.
26. Ventura, A., E. Neri, C. Ughi, A. Leopaldi, A. Città, and T. Not. 2000. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J. Pediatr. 137: 263-265. (Pubitemid 30659239)
27. Füchtenbusch, M., A. G. Ziegler, and M. Hummel. 2004. Elimination of dietary gluten and development of type 1 diabetes in high risk subjects. Rev. Diabet. Stud. 1: 39-41.
28. Bosi, E., M. R. Pastore, L. Molteni, E. Bazzigaluppi, E. Bonifacio, and L. Piemonti. 2005. Gluten-free diet in subjects at risk for type 1 diabetes: a tool for delaying progression to clinical disease? Adv. Exp. Med. Biol. 569: 157-158. (Pubitemid 43779620)
29. Funda, D. P., A. Kaas, T. Bock, H. Tlaskalová-Hogenová, and K. Buschard. 1999. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab. Res. Rev. 15: 323-327. (Pubitemid 29535091)
30. Kudva, Y. C., G. Rajagopalan, R. Raju, R. S. Abraham, M. Smart, J. Hanson, and C. S. David. 2002. Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II. Hum. Immunol. 63: 987-999. (Pubitemid 35231682)
31. Giarratana, N., G. Penna, and L. Adorini. 2007. Animal models of spontaneous autoimmune disease: type 1 diabetes in the nonobese diabetic mouse. Methods Mol. Biol. 380: 285-311. (Pubitemid 350183335)
32. Cheţa, D. 1998. Animal models of type I (insulin-dependent) diabetes mellitus. J. Pediatr. Endocrinol. Metab. 11: 11-19. (Pubitemid 28110748)
33. Marietta, E., K. Black, M. Camilleri, P. Krause, R. S. Rogers, III, C. David, M. R. Pittelkow, and J. A. Murray. 2004. A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice. J. Clin. Invest. 114: 1090-1097. (Pubitemid 39578698)
34. Rajagopalan, G., Y. C. Kudva, R. A. Flavell, and C. S. David. 2003. Accelerated diabetes in rat insulin promoter-tumor necrosis factor-alpha transgenic nonobese diabetic mice lacking major histocompatibility class II molecules. Diabetes 52: 342-347. (Pubitemid 36173188)
35. Thomas, K. E., A. Sapone, A. Fasano, and S. N. Vogel. 2006. Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J. Immunol. 176: 2512-2521. (Pubitemid 43201702)
36. Bollyky, P. L., J. B. Bice, I. R. Sweet, B. A. Falk, J. A. Gebe, A. E. Clark, V. H. Gersuk, A. Aderem, T. R. Hawn, and G. T. Nepom. 2009. The toll-like receptor signaling molecule Myd88 contributes to pancreatic beta-cell homeostasis in response to injury. PLoS ONE 4: e5063.
37. Biagi, F., O. Luinetti, J. Campanella, C. Klersy, C. Zambelli, V. Villanacci, A. Lanzini, and G. R. Corazza. 2004. Intraepithelial lymphocytes in the villous tip: do they indicate potential coeliac disease? J. Clin. Pathol. 57: 835-839. (Pubitemid 39061432)
38. Goudy, K. S., B. R. Burkhardt, C. Wasserfall, S. Song, M. L. Campbell-Thompson, T. Brusko, M. A. Powers, M. J. Clare-Salzler, E. S. Sobel, T. M. Ellis, et al. 2003. Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion. J. Immunol. 171: 2270-2278. (Pubitemid 37025531)
39. Leiter, E. H. 2001. The NOD mouse: a model for insulin-dependent diabetes mellitus. Curr. Protoc. Immunol. Chapter 15: Unit 15.9.
40. Esensten, J. H., M. R. Lee, L. H. Glimcher, and J. A. Bluestone. 2009. T-bet-deficient NOD mice are protected from diabetes due to defects in both T cell and innate immune system function. J. Immunol. 183: 75-82.
41. Verdu, E. F., X. Huang, J. Natividad, J. Lu, P. A. Blennerhassett, C. S. David, D. M. McKay, and J. A. Murray. 2008. Gliadin-dependent neuromuscular and epithelial secretory responses in gluten-sensitive HLA-DQ8 transgenic mice. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G217-G225.
42. de Kauwe, A. L., Z. Chen, R. P. Anderson, C. L. Keech, J. D. Price, O. Wijburg, D. C. Jackson, J. Ladhams, J. Allison, and J. McCluskey. 2009. Resistance to celiac disease in humanized HLA-DR3-DQ2-transgenic mice expressing specific anti-gliadin CD4+ T cells. J. Immunol. 182: 7440-7450.
43. Natividad, J. M., X. Huang, E. Slack, J. Jury, Y. Sanz, C. David, E. Denou, P. Yang, J. Murray, K. D. McCoy, and E. F. Verdú. 2009. Host responses to intestinal microbial antigens in gluten-sensitive mice. PLoS ONE 4: e6472.
44. Parish, C. R., M. H. Glidden, B. J. Quah, and H. S. Warren. 2001. Use of the intracellular fluorescent dye CFSE to monitor lymphocyte migration and proliferation. Curr. Protoc. Immunol. 4: 4.9.
45. Black, K. E., J. A. Murray, and C. S. David. 2002. HLA-DQ determines the response to exogenous wheat proteins: a model of gluten sensitivity in transgenic knockout mice. J. Immunol. 169: 5595-5600. (Pubitemid 35291659)
46. Green, P. H. R., K. Rostami, and M. N. Marsh. 2005. Diagnosis of coeliac disease. Best Pract. Res. Clin. Gastroenterol. 19: 389-400. (Pubitemid 40753760)
47. McNeill, A., E. Spittle, and B. T. Bäckström. 2007. Partial depletion of CD69low-expressing natural regulatory T cells with the anti-CD25 monoclonal antibody PC61. Scand. J. Immunol. 65: 63-69. (Pubitemid 44968073)
48. Morris, G. P., N. K. Brown, and Y. C. Kong. 2009. Naturally-existing CD4(+) CD25(+)Foxp3(+) regulatory T cells are required for tolerance to experimental autoimmune thyroiditis induced by either exogenous or endogenous autoantigen. J. Autoimmun. 33: 68-76.
49. Setiady, Y. Y., J. A. Coccia, and P. U. Park. 2009. In vivo depletion of CD4+ FOXP3+ Treg cells by the PC61 anti-CD25 monoclonal antibody is mediated by FcγRIII+ phagocytes. Eur. J. Immunol. 40: 780-786.
50. Sakaguchi, S., M. Ono, R. Setoguchi, H. Yagi, S. Hori, Z. Fehervari, J. Shimizu, T. Takahashi, and T. Nomura. 2006. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol. Rev. 212: 8-27. (Pubitemid 44116697)
51. Piccirillo, C. A., and A. M. Thornton. 2004. Cornerstone of peripheral tolerance: naturally occurring CD4+CD25+ regulatory T cells. Trends Immunol. 25: 374-380. (Pubitemid 38780954)
52. Horwitz, D. A., S. G. Zheng, and J. D. Gray. 2008. Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol. 29: 429-435.
53. McHugh, R. S., and E. M. Shevach. 2002. Cutting edge: depletion of CD4+ CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. J. Immunol. 168: 5979-5983. (Pubitemid 34620008)
54. Hadjivassiliou, M., D. S. Sanders, R. A. Grünewald, N. Woodroofe, S. Boscolo, and D. Aeschlimann. 2010. Gluten sensitivity: from gut to brain. Lancet Neurol. 9: 318-330.
55. Fox, C. J., and J. S. Danska. 1998. Independent genetic regulation of T-cell and antigen-presenting cell participation in autoimmune islet inflammation. Diabetes 47: 331-338. (Pubitemid 28104192)
56. Montero, E., G. Nussbaum, J. F. Kaye, R. Perez, A. Lage, A. Ben-Nun, and I. R. Cohen. 2004. Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies. J. Autoimmun. 23: 1-7. (Pubitemid 38953787)
57. Senger, S., F. Maurano, M. F. Mazzeo, M. Gaita, O. Fierro, C. S. David, R. Troncone, S. Auricchio, R. A. Siciliano, and M. Rossi. 2005. Identification of immunodominant epitopes of alpha-gliadin in HLA-DQ8 transgenic mice following oral immunization. J. Immunol. 175: 8087-8095. (Pubitemid 41798371)
58. Hänninen, A., M. Salmi, O. Simell, and S. Jalkanen. 1996. Mucosa-associated (beta 7-integrinhigh) lymphocytes accumulate early in the pancreas of NOD mice and show aberrant recirculation behavior. Diabetes 45: 1173-1180. (Pubitemid 26296315)
59. Hänninen, A., I. Jaakkola, and S. Jalkanen. 1998. Mucosal addressin is required for the development of diabetes in nonobese diabetic mice. J. Immunol. 160: 6018-6025. (Pubitemid 28298064)
60. Taneja, V., M. Behrens, L. T. Cooper, S. Yamada, H. Kita, M. M. Redfield, A. Terzic, and C. David. 2007. Spontaneous myocarditis mimicking human disease occurs in the presence of an appropriate MHC and non-MHC background in transgenic mice. J. Mol. Cell. Cardiol. 42: 1054-1064. (Pubitemid 46829194)
61. Vaarala, O. 2008. Leaking gut in type 1 diabetes. Curr. Opin. Gastroenterol. 24: 701-706.
62. Visser, J., J. Rozing, A. Sapone, K. Lammers, and A. Fasano. 2009. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann. N. Y. Acad. Sci. 1165: 195-205.
63. Neu, J., C. M. Reverte, A. D. Mackey, K. Liboni, L. M. Tuhacek-Tenace, M. Hatch, N. Li, R. A. Caicedo, D. A. Schatz, and M. Atkinson. 2005. Changes in intestinal morphology and permeability in the biobreeding rat before the onset of type 1 diabetes. J. Pediatr. Gastroenterol. Nutr. 40: 589-595. (Pubitemid 40617187)
64. Graham, S., P. Courtois, W. J. Malaisse, J. Rozing, F. W. Scott, and A. M. Mowat. 2004. Enteropathy precedes type 1 diabetes in the BB rat. Gut 53: 1437-1444. (Pubitemid 39265262)
65. Watts, T., I. Berti, A. Sapone, T. Gerarduzzi, T. Not, R. Zielke, and A. Fasano. 2005. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc. Natl. Acad. Sci. USA 102: 2916-2921. (Pubitemid 40299891)
66. Sapone, A., L. de Magistris, M. Pietzak, M. G. Clemente, A. Tripathi, F. Cucca, R. Lampis, D. Kryszak, M. Cartenì, M. Generoso, et al. 2006. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55: 1443-1449. (Pubitemid 44195385)
67. Bosi, E., L. Molteni, M. G. Radaelli, L. Folini, I. Fermo, E. Bazzigaluppi, L. Piemonti, M. R. Pastore, and R. Paroni. 2006. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 49: 2824-2827. (Pubitemid 44730283)
68. Lee, A. S., D. L. Gibson, Y. Zhang, H. P. Sham, B. A. Vallance, and J. P. Dutz. 2010. Gut barrier disruption by an enteric bacterial pathogen accelerates insulitis in NOD mice. Diabetologia 53: 741-748.
69. Vogelsang, H., M. Schwarzenhofer, and G. Oberhuber. 1998. Changes in gastrointestinal permeability in celiac disease. Dig. Dis. 16: 333-336. (Pubitemid 128525938)
70. Drago, S., R. El Asmar, M. Di Pierro, M. Grazia Clemente, A. Tripathi, A. Sapone, M. Thakar, G. Iacono, A. Carroccio, C. D'Agate, et al. 2006. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand. J. Gastroenterol. 41: 408-419. (Pubitemid 43675406)
71. Clemente, M. G., S. De Virgiliis, J. S. Kang, R. Macatagney, M. P. Musu, M. R. Di Pierro, S. Drago, M. Congia, and A. Fasano. 2003. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 52: 218-223. (Pubitemid 36115062)
72. Ventura, A., G. Magazzù, L. Greco; SIGEP Study Group for Autoimmune Disorders in Celiac Disease. 1999. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology 117: 297-303. (Pubitemid 29352936)
73. Pastore, M. R., E. Bazzigaluppi, C. Belloni, C. Arcovio, E. Bonifacio, and E. Bosi. 2003. Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J. Clin. Endocrinol. Metab. 88: 162-165. (Pubitemid 36115159)
74. Toscano, V., F. G. Conti, E. Anastasi, P. Mariani, C. Tiberti, M. Poggi, M. Montuori, S. Monti, S. Laureti, E. Cipolletta, et al. 2000. Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients. Am. J. Gastroenterol. 95: 1742-1748. (Pubitemid 30485012)
75. Marsh, M. N. 1992. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology 102: 330-354.
76. DePaolo, R. W., V. Abadie, F. Tang, H. Fehlner-Peach, J. A. Hall, W. Wang, E. V. Marietta, D. D. Kasarda, T. A. Waldmann, J. A. Murray, et al. 2011. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471: 220-224.
77. Hadis, U., B. Wahl, O. Schulz, M. Hardtke-Wolenski, A. Schippers, N. Wagner, W. Müller, T. Sparwasser, R. Fö rster, and O. Pabst. 2011. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 34: 237-246.
78. Zheng, S. G., J. Wang, P. Wang, J. D. Gray, and D. A. Horwitz. 2007. IL-2 is essential for TGF-beta to convert naive CD4+CD25- cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells. J. Immunol. 178: 2018-2027. (Pubitemid 46233398)
79. Planas, R., A. Alba, J. Carrillo, M. C. Puertas, R. Ampudia, X. Pastor, H. Okamoto, S. Takasawa, W. Gurr, R. Pujol-Borrell, et al. 2006. Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta. Diabetologia 49: 2379-2387. (Pubitemid 44359099)
80. Wen, L., F. S. Wong, J. Tang, N. Y. Chen, M. Altieri, C. David, R. Flavell, and R. Sherwin. 2000. In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes. J. Exp. Med. 191: 97-104. (Pubitemid 30043651)
81. Stewart, T. A., B. Hultgren, X. Huang, S. Pitts-Meek, J. Hully, and N. J. MacLachlan. 1993. Induction of type I diabetes by interferon-alpha in transgenic mice. Science 260: 1942-1946. (Pubitemid 23258275)
82. Hänninen, A., M. Salmi, O. Simell, D. Andrew, and S. Jalkanen. 1996. Recirculation and homing of lymphocyte subsets: dual homing specificity of beta 7-integrin(high)-lymphocytes in nonobese diabetic mice. Blood 88: 934-944. (Pubitemid 26333317)
83. Hänninen, A., R. Nurmela, M. Maksimow, J. Heino, S. Jalkanen, and C. Kurts. 2007. Islet beta-cell-specific T cells can use different homing mechanisms to infiltrate and destroy pancreatic islets. Am. J. Pathol. 170: 240-250. (Pubitemid 47339203)
84. Jaakkola, I., S. Jalkanen, and A. Hänninen. 2003. Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD mice. Eur. J. Immunol. 33: 3255-3264. (Pubitemid 37541101)
85. Patterson, C. C., G. G. Dahlquist, E. Gyürüs, A. Green, and G. Soltész; EURODIAB Study Group. 2009. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet 373: 2027-2033.
86. Green, P. H. 2007. Where are all those patients with Celiac disease? Am. J. Gastroenterol. 102: 1461-1463. (Pubitemid 46976275)
87. Johnson, J. A., S. L. Pohar, and S. R. Majumdar. 2006. Health care use and costs in the decade after identification of type 1 and type 2 diabetes: a population-based study. Diabetes Care 29: 2403-2408. (Pubitemid 44912243)
88. Pinier, M., E. F. Verdu, M. Nasser-Eddine, C. S. David, A. Vézina, N. Rivard, and J. C. Leroux. 2009. Polymeric binders suppress gliadin-induced toxicity in the intestinal epithelium. Gastroenterology 136: 288-298.