Immune cell crosstalk in type 1 diabetes

Nature Reviews Immunology

Volumn 10, Issue 7, 2010, Pages 501-513

  Lehuen, Agnès ^a   Diana, Julien ^a   Zaccone, Paola ^b   Cooke, Anne ^b  

^a HÔPITAL SAINT VINCENT DE PAUL   (France)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; AUTOIMMUNITY; CROSS LINKING; DENDRITIC CELL; DIABETOGENESIS; HUMAN; IMMUNOCOMPETENT CELL; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; MACROPHAGE; MOLECULAR MIMICRY; NATURAL KILLER CELL; NONHUMAN; PANCREAS ISLET BETA CELL; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; VIRUS INFECTION;

ANIMALS; AUTOIMMUNITY; DENDRITIC CELLS; DIABETES MELLITUS, TYPE 1; HUMANS; IMMUNITY, INNATE; INFECTION; INSULIN-SECRETING CELLS; KILLER CELLS, NATURAL; LYMPHOCYTE ACTIVATION; LYMPHOCYTES; MICE; MODELS, IMMUNOLOGICAL; NATURAL KILLER T-CELLS; RATS;

EID: 77954128990     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri2787     Document Type: Review

References (144)

1. Banting, F. G. & Best, C. H. The internal secretion of the pancreas. J. Lab. Clin. Med. 7, 465-480 (1922).
2. Redondo, M. J., Fain, P. R. & Eisenbarth, G. S. Genetics of type 1A diabetes. Recent Prog. Horm. Res. 56, 69-89 (2001).
3. Kyvik, K. O., Green, A. & Beck-Nielsen, H. Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ 3 11, 913-917 (1995).
4. Redondo, M. J., Jeffrey, J., Fain, P. R., Eisenbarth, G. S. & Orban, T. Concordance for islet autoimmunity among monozygotic twins. N. Engl. J. Med. 359, 2849-2850 (2008).
5. Dunne, D. W. & Cooke, A. A worm's eye view of the immune system: consequences for evolution of human autoimmune disease. Nature Rev. Immunol. 5, 420-426 (2005).
6. Turley, S., Poirot, L., Hattori, M., Benoist, C. & Mathis, D. Physiological β cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J. Exp. Med. 198, 1527-1537 (2003)
7. Barrett, J. C. et al. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genet. 41, 703-707 (2009).
8. Reimann, M. et al. An update on preventive and regenerative therapies in diabetes mellitus. Pharmacol. Ther. 121, 317-331 (2009).
9. Hyoty, H. et al. Decline of mumps antibodies in type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of type 1 diabetes after introduction of the mumps-measles-rubella vaccine in Finland. Childhood Diabetes in Finland Study Group. Diabetologia 36, 1303-1308 (1993).
10. von Herrath, M. G., Fujinami, R. S. & Whitton, J. L. Microorganisms and autoimmunity: making the barren field fertile? Nature Rev. Microbiol. 1,151-157 (2003).
11. Sibley, R. K., Sutherland, D. E., Goetz, F. & Michael, A. F. Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab. Invest. 53, 132-144 (1985).
12. + T cells and can be reversed by non-depleting antibodies targeting both T cell populations. Rev. Diabet. Stud. 6, 97-103 (2009).
13. Chatenoud, L., Thervet, E., Primo, J. & Bach, J. F. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc. Natl Acad. Sci. USA 91, 123-127 (1994).
14. Chatenoud, L. Immune therapy for type 1 diabetes mellitus\what is unique about anti-CD3 antibodies? Nature Rev. Endocrinol. 6, 149-157 (2010).
15. Eizirik, D. L., Colli, M. L. & Ortis, F. The role of inflammation in insulitis and β cell loss in type 1 diabetes. Nature Rev. Endocrinol. 5, 219-226 (2009).
16. Wildin, R. S. & Freitas, A. IPEX and FOXP3: clinical and research perspectives. J. Autoimmun. 25, S56-S62 (2005).
17. + immunoregulatory T cells that control autoimmune diabetes. Immunity 12, 431-440 (2000).
18. + regulatory T cell: a jack of all trades, master of regulation. Nature Immunol. 9, 239-244 (2008).
19. Hu, C. Y. et al. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J. Clin. Invest. 11 7, 3857-3867 (2007).
20. null mice. J. Exp. Med. 184, 2049-2053 (1996).
21. Pescovitz, M. D. et al. Rituximab, B-lymphocyte depletion, and preservation of β-cell function. N. Engl. J. Med. 361, 2143-2152 (2009).
22. Martin, S. et al. Development of type 1 diabetes despite severe hereditary B-lymphocyte deficiency. N. Engl. J. Med. 345, 1036-1040 (2001).
23. Xiu, Y. et al. B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in FcyR effector functions. J. Immunol. 180, 2863-2875 (2008).
24. Hutchings, P. et al. Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Nature 348, 639-642 (1990).
25. Jun, H. S., Yoon, C. S., Zbytnuik, L, van Rooijen, N. & Yoon, J. W. The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. J. Exp. Med. 189, 347-358 (1999).
26. Alleva, D. G., Pavlovich, R. P., Grant, C, Kaser, S. B. & Beller, D. I. Aberrant macrophage cytokine production is a conserved feature among autoimmune-prone mouse strains: elevated interleukin (IL)-12 and an imbalance in tumor necrosis factor-a and IL-10 define a unique cytokine profile in macrophages from young nonobese diabetic mice. Diabetes 49, 1106-1115 (2000).
27. Martin, A. P. et al. Increased expression of CCL2 in insulin-producing cells of transgenic mice promotes mobilization of myeloid cells from the bone marrow, marked insulitis, and diabetes. Diabetes 57, 3025-3033 (2008).
28. Yang, L. J. Big mac attack: does it play a direct role for monocytes/macrophages in type 1 diabetes? Diabetes 57, 2922-2923 (2008).
29. Arnush, M., Scarim, A. L, Heitmeier, M. R., Kelly, C. B. & Corbett, J. A. Potential role of resident islet macrophage activation in the initiation of autoimmune diabetes. J. Immunol. 160, 2684-2691 (1998).
30. Dahlen, E., Dawe, K., Ohlsson, L. & Hedlund, G. Dendritic cells and macrophages are the first and major producers of TNF-a in pancreatic islets in the nonobese diabetic mouse. J. Immunol. 160, 3585-3593 (1998).
31. Cantor, J. & Haskins, K. Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: evidence for involvement of CCR8 and CCL1. J. Immunol. 179, 5760-5767 (2007).
32. Uno, S. et al. Macrophages and dendritic cells infiltrating islets with or without (3 cells produce tumour necrosis factor-a in patients with recent-onset type 1 diabetes. Diabetologia 50, 596-601 (2007).
33. Dotta, F. et al. Coxsackie B4 virus infection of (3 cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc. Natl Acad. Sci. USA 104, 5115-5120 (2007).
34. Flodstrom, M. et al. Target cell defense prevents the development of diabetes after viral infection. Nature Immunol. 3, 373-382 (2002).
35. Poirot, L, Benoist, C. & Mathis, D. Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity. Proc. Natl Acad. Sci. USA 101, 8102-8107 (2004).
36. Alba, A. et al. Natural killer cells are required for accelerated type 1 diabetes driven by interferon-(3. Clin. Exp. Immunol. 151, 467-475 (2008).
37. Brauner, H. et al. Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice. J. Immunol. 184, 2272-2280 (2010).
38. Feuerer, M., Shen, Y., Littman, D. R., Benoist, C. & Mathis, D. How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity 31, 654-664 (2009).
39. Gur, C. et al. The activating receptor NKp46 is essential for the development of type 1 diabetes. Nature Immunol. 11, 121-128 (2010).
40. Ogasawara, K. et al. NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity 20, 757-767 (2004).
41. Lacy, P. E., Davie, J. M. & Finke, E. H. Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS. Science 204, 312-313 (1979).
42. Faustman, D. L. et al. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc. Natl Acad. Sci. USA 81, 3864-3868 (1984).
43. Ludewig, B., Odermatt, B., Landmann, S., Hengartner, H. & Zinkernagel, R. M. Dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissue. J. Exp. Med. 188, 1493-1501 (1998).
44. Marleau, A. M., Summers, K. L. & Singh, B. Differential contributions of APC subsets to T cell activation in nonobese diabetic mice. J. Immunol. 180, 5235-5249 (2008).
45. Kim, H. S. et al. Toll-like receptor 2 senses (3-cell death and contributes to the initiation of autoimmune diabetes. Immunity 27, 321-333 (2007).
46. Wen, L. et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 1109-1113 (2008).
47. Poligone, B., Weaver, D. J. Jr, Sen, P., Baldwin, A. S. Jr & Tisch, R. Elevated NF-KB activation in nonobese diabetic mouse dendritic cells results in enhanced APC function. J. Immunol. 168, 188-196 (2002).
48. Steptoe, R. J., Ritchie, J. M. & Harrison, L. C. Increased generation of dendritic cells from myeloid progenitors in autoimmune-prone nonobese diabetic mice. J. Immunol. 168, 5032-5041 (2002).
49. Lande, R. & Gilliet, M. Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann. NY Acad. Sci. 1183, 89-103 (2010).
50. Stewart, T. A. et al. Induction of type I diabetes by interferon-a in transgenic mice. Science 260, 1942-1946 (1993).
51. Huang, Y., Blatt, L. M. & Taylor, M. W Type 1 interferon as an antiinflammatory agent: inhibition of lipopolysaccharide-induced interleukin-1 (3 and induction of interleukin-1 receptor antagonist. J. Interferon Cytokine Res. 15, 317-321 (1995).
52. Li, Q. et al. Interferon-a initiates type 1 diabetes in nonobese diabetic mice. Proc. Natl Acad. Sci. USA 105, 12439-12444 (2008).
53. Van Belle, T L, Juntti, T., Liao, J. & von Herrath, M. G. Pre-existing autoimmunity determines type 1 diabetes outcome after Flt3-ligand treatment. J. Autoimmun. 34, 445-452 (2009).
54. Vuckovic, S. et al. Decreased blood dendritic cell counts in type 1 diabetic children. Clin. Immunol. 123, 281-288 (2007).
55. Chen, X. et al. Type 1 diabetes patients have significantly lower frequency of plasmacytoid dendritic cells in the peripheral blood. Clin. Immunol. 129, 413-418 (2008).
56. Allen, J. S. et al. Plasmacytoid dendritic cells are proportionally expanded at diagnosis of type 1 diabetes and enhance islet autoantigen presentation to T-cells through immune complex capture. Diabetes 58, 138-145 (2009).
57. Ohnmacht, C. et al. Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J. Exp. Med. 206, 549-559 (2009).
58. Ueno, H. et al. Dendritic cell subsets in health and disease. Immunol. Rev. 219, 118-142 (2007).
59. + regulatory T-cells. Diabetes 54, 78-84 (2005).
60. Chilton, P. M. et al. Flt3-ligand treatment prevents diabetes in NOD mice. Diabetes 53, 1995-2002 (2004).
61. O'Keeffe, M. et al. Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development. Int. Immunol. 17, 307-314 (2005).
62. Darrasse-Jeze, G. et al. Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J. Exp. Med. 206, 1853-1862 (2009).
63. Saxena, V., Ondr, J. K., Magnusen, A. F., Munn, D. H. & Katz, J. D. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse. J. Immunol. 179, 5041-5053 (2007).
64. Grohmann, U. et al. A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice. J. Exp. Med. 198, 153-160 (2003).
65. Alexander, A. M. et al. Indoleamine 2, 3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes 51, 356-365 (2002).
66. Diana, J. et al. NKT Cell-plasmacytoid dendritic cell cooperation via OX40 controls viral infection in a tissue-specific manner. Immunity 30, 289-299 (2009).
67. Carnaud, C., Gombert, J., Donnars, O., Garchon, H. & Herbelin, A. Protection against diabetes and improved NK/NKT cell performance in NOD.NK1.1 mice congenic at the NK complex. J. Immunol. 166, 2404-2411 (2001).
68. Ogasawara, K. et al. Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity 18, 41-51 (2003).
69. Rodacki, M. et al. Altered natural killer cells in type 1 diabetic patients. Diabetes 56, 177-185 (2007).
70. Lee, I. F., Qin, H., Trudeau, J., Dutz, J. & Tan, R. Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells. J. Immunol. 172, 937-942 (2004).
71. Beilke, J. N., Kuhl, N. R., Van Kaer, L. & Gill, R. G. NK cells promote islet allograft tolerance via a perforin-dependent mechanism. Nature Med. 11, 1059-1065 (2005).
72. Novak, J., Griseri, T., Beaudoin, L. & Lehuen, A. Regulation of type 1 diabetes by NKT cells. Int. Rev. Immunol. 26, 49-72 (2007).
73. - (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. J. Exp. Med. 187, 1047-1056 (1998).
74. Lehuen, A. et al. Overexpression of natural killer T cells protects Vα14-Jα281 transgenic nonobese diabetic mice against diabetes. J. Exp. Med. 188, 1831-1839 (1998).
75. Sharif, S. et al. Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune type 1 diabetes. Nature Med. 7, 1057-1062 (2001).
76. Hong, S. et al. The natural killer T-cell ligand α- galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nature Med. 7, 1052-1056 (2001).
77. Mizuno, M. et al. Synthetic glycolipid OCH prevents insulitis and diabetes in NOD mice. J. Autoimmun 23, 293-300 (2004).
78. Forestier, C. et al. Improved outcomes in NOD mice treated with a novel Th2 cytokine-biasing NKT cell activator. J. Immunol. 178, 1415-1425 (2007).
79. Laloux, V., Beaudoin, L., Jeske, D., Carnaud, C. & Lehuen, A. NK T cell-induced protection against diabetes in Vα14-Jα281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen. J. Immunol. 166, 3749-3756 (2001).
80. Beaudoin, L., Laloux, V., Novak, J., Lucas, B. & Lehuen, A. NKT cells inhibit the onset of diabetes by impairing the development of pathogenic T cells specific for pancreatic β cells. Immunity 17, 725-736 (2002).
81. Chen, Y. G. et al. Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J. Immunol. 174, 1196-1204 (2005).
82. Duarte, N. et al. Prevention of diabetes in nonobese diabetic mice mediated by CD1d-restricted nonclassical NKT cells. J. Immunol. 173, 3112-3118 (2004).
83. Jordan, M. A., Fletcher, J. M., Pellicci, D. & Baxter, A. G. Slamf1, the NKT cell control gene Nkt1. J. Immunol. 178, 1618-1627 (2007).
84. + T-cells observed in type 1 diabetes. Diabetes Care 25, 1818-1823 (2002).
85. Kukreja, A. et al. Multiple immuno-regulatory defects in type-1 diabetes. J. Clin. Invest. 109, 131-140 (2002).
86. Kato, H. et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101-105 (2006).
87. Nejentsev, S., Walker, N., Riches, D., Egholm, M. & Todd, J. A. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324, 387-389 (2009).
88. Yoon, J. W., McClintock, P. R., Onodera, T. & Notkins, A. L. Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus. J. Exp. Med. 152, 878-892 (1980).
89. Baek, H. S. & Yoon, J. W. Direct involvement of macrophages in destruction of (3-cells leading to development of diabetes in virus-infected mice. Diabetes 40, 1586-1597 (1991).
90. Lee, Y. S., Li, N., Shin, S. & Jun, H. S. Role of nitric oxide in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. J. Virol. 83, 8004-8011 (2009).
91. Shibasaki, S. et al. Expression of Toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes. Endocr. J. 23, 211-219 (2009).
92. Atkinson, M. A. et al. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J. Clin. Invest. 94, 2125-2129 (1994).
93. Honeyman, M. C, Stone, N. L., Falk, B. A., Nepom, G. & Harrison, L. C. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J. Immunol. 184, 2204-22 10 (2010).
94. Ou, D., Mitchell, L. A., Metzger, D. L, Gillam, S. & Tingle, A. J. Cross-re active rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus. Diabetologia 43, 750-762 (2000).
95. Pak, C. Y, Cha, C. Y., Rajotte, R. V, McArthur, R. G. & Yoon, J. W. Human pancreatic islet cell specific 38 kilodalton autoantigen identified by cytomegalovirus-induced monoclonal islet cell autoantibody. Diabetologia 33, 569-572 (1990).
96. Oldstone, M. B., Nerenberg, M., Southern, P., Price, J. & Lewicki, H. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65, 319-331 (1991).
97. Ohashi, P. S. et al. Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65, 305-317 (1991).
98. Seewaldt, S. et al. Virus-induced autoimmune diabetes: most (3-cells die through inflammatory cytokines and not perforin from autoreactive (antiviral) cytotoxic T-lymphocytes. Diabetes 49, 1801-1809 (2000).
99. Christen, U. et al. A dual role for TNF-a in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. J. Immunol. 166, 7023-7032 (2001).
100. Christen, U., McGavern, D. B., Luster, A. D., von Herrath, M. G. & Oldstone, M. B. Among CXCR3 chemokines, IFN-y-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-y (CXCL9) imprints a pattern for the subsequent development of autoimmune disease. J. Immunol. 171, 6838-6845 (2003).
101. Horwitz, M. S. et al. Diabetes induced by coxsackie virus: initiation by bystander damage and not molecular mimicry. Nature Med. 4, 781-785 (1998).
102. Katz, J. D., Wang, B., Haskins, K., Benoist, C. & Mathis, D. Following a diabetogenic T cell from genesis through pathogenesis. Cell 74, 1089-1100 (1993).
103. Stadinski, B. D. et al. Chromogranin A is an autoantigen in type 1 diabetes. Nature Immunol. 11, 225-231 (2010).
104. Serreze, D. V, Ottendorfer, E. W, Ellis, T. M., Gauntt, C. J. & Atkinson, M. A. Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets. Diabetes 49, 708-711 (2000).
105. Drescher, K. M., Kono, K., Bopegamage, S., Carson, S. D. & Tracy, S. Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: insulitis determines susceptibility of pancreatic islets to virus infection. Virology 329, 381-394 (2004).
106. Horwitz, M. S., Ilic, A., Fine, C., Rodriguez, E. & Sarvetnick, N. Presented antigen from damaged pancreatic β cells activates autoreactive T cells in virus-mediated autoimmune diabetes. J. Clin. Invest. 109, 79-87 (2002).
107. Horwitz, M. S., Ilic, A., Fine, C., Balasa, B. & Sarvetnick, N. Coxsackieviral-mediated diabetes: induction requires antigen-presenting cells and is accompanied by phagocytosis of β cells. Clin. Immunol. 110, 134-144 (2004).
108. Graham, K. L. et al. Rotavirus infection of infant and young adult nonobese diabetic mice involves extraintestinal spread and delays diabetes onset. J. Virol. 81, 6446-6458 (2007).
109. Graham, K. L. et al. Rotavirus infection accelerates type 1 diabetes in mice with established insulitis. J. Virol. 82, 6139-6149 (2008).
110. Serreze, D. V. et al. Diabetes acceleration or prevention by a coxsackievirus B4 infection: critical requirements for both interleukin-4 and γ interferon. J. Virol. 79, 1045-1052 (2005).
111. Filippi, C. M., Estes, E. A., Oldham, J. E. & von Herrath, M. G. Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice. J. Clin. Invest. 11 9, 1515-1523 (2009).
112. Ansari, M. J. et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J. Exp. Med. 198, 63-69 (2003).
113. Diana, J. & Lehuen, A. NKT cells: Friend or foe during viral infections? Eur. J. Immunol. 39, 3283-3291 (2009).
114. Serreze, D. V., Hamaguchi, K. & Leiter, E. H. Immunostimulation circumvents diabetes in NOD/Lt mice. J. Autoimmun. 2, 759-776 (1989).
115. Lee, B. J. et al. Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice. Yonsei Med. J. 46, 341-346 (2005).
116. Quintana, F. J., Rotem, A., Carmi, P. & Cohen, I. R. Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity. J. Immunol. 165, 6148-6155 (2000).
117. Fallarino, F. et al. IDO mediates TLR9-driven protection from experimental autoimmune diabetes. J. Immunol. 183, 6303-6312 (2009).
118. Wen, L., Peng, J., Li, Z. & Wong, F. S. The effect of innate immunity on autoimmune diabetes and the expression of Toll-like receptors on pancreatic islets. J. Immunol. 172, 3173-3180 (2004).
119. Bras, A. & Aguas, A. P. Diabetes-prone NOD mice are resistant to Mycobacterium avium and the infection prevents autoimmune disease. Immunology 89, 20-25 (1996).
120. Baxter, A. G., Healey, D. & Cooke, A. Mycobacteria precipitate autoimmune rheumatic disease in NOD mice via an adjuvant-like activity. Scand. J. Immunol. 39, 602-606 (1994).
121. Harada, M., Kishimoto, Y. & Makino, S. Prevention of overt diabetes and insulitis in NOD mice by a single BCG vaccination. Diabetes Res. Clin. Pract. 8, 85-89 (1990).
122. Sadelain, M. W., Qin, H. Y., Lauzon, J. & Singh, B. Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. Diabetes 39, 583-589 (1990).
123. Zaccone, P. et al. Salmonella typhimurium infection halts development of type 1 diabetes in NOD mice. Eur. J. Immunol. 34, 3246-3256 (2004).
124. Raine, T., Zaccone, P., Mastroeni, P. & Cooke, A. Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes. J. Immunol. 177, 2224-2233 (2006).
125. Sarkar, S. A. et al. Induction of indoleamine 2, 3-dioxygenase by interferon-γ in human islets. Diabetes 56, 72-79 (2007).
126. Sai, P. & Rivereau, A. S. Prevention of diabetes in the nonobese diabetic mouse by oral immunological treatments. Comparative efficiency of human insulin and two bacterial antigens, lipopolysacharide from Escherichia coli and glycoprotein extract from Klebsiella pneumoniae. Diabetes Metab. 22, 341-348 (1996).
127. Karumuthil-Melethil, S., Perez, N., Li, R. & Vasu, C. Induction of innate immune response through TLR2 and dectin 1 prevents type 1 diabetes. J. Immunol. 181, 8323-8334 (2008).
128. Zaccone, P. et al. Immune modulation by Schistosoma mansoni antigens in NOD mice: effects on both innate and adaptive immune systems. J. Biomed. Biotechnol. 2010, 795210 (2010).
129. Zaccone, P. et al. Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur. J. Immunol. 39, 1098-1107 (2009)
130. Cooke, A. et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 21, 169-176 (1999).
131. Zaccone, P. et al. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur. J. Immunol. 33, 1439-1449 (2003).
132. Yoon, J. W., Austin, M., Onodera, T. & Notkins, A. L. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N. Engl. J. Med. 300, 1173-1179 (1979).
133. Tirabassi, R. S. et al. Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization. Diabetes 59, 110-118 (2010).
134. + T cell populations. J. Immunol. 170, 3592-3602 (2003).
135. Oldstone, M. B. Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence. J. Exp. Med. 171, 2077-2089 (1990).
136. Takei, I. et al. Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection. J. Autoimmun. 5, 665-673 (1992).
137. Wilberz, S., Partke, H. J., Dagnaes-Hansen, F. & Herberg, L. Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice. Diabetologia 34, 2-5 (1991).
138. Smith, K. A., Efstathiou, S. & Cooke, A. Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice. J. Immunol. 179, 7325-7333 (2007).
139. + T cells and costimulatory pathways of T-cell activation in protection of non-obese diabetic (NOD) mice from diabetes. Immunology 96, 600-605 (1999).
140. Toyota, T., Satoh, J., Oya, K., Shintani, S. & Okano, T. Streptococcal preparation (OK-432) inhibits development of type I diabetes in NOD mice. Diabetes 35, 496-499 (1986).
141. Alyanakian, M. A. et al. Transforming growth factor-beta and natural killer T-cells are involved in the protective effect of a bacterial extract on type 1 diabetes. Diabetes 55, 179-185 (2006).
142. Saunders, K. A., Raine, T., Cooke, A. & Lawrence, C. E. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect. Immun. 75, 397-407 (2007).
143. + regulatory T cells. Immunology 127, 512-522 (2009).
144. Imai, S., Tezuka, H. & Fujita, K. A factor of inducing IgE from a filarial parasite prevents insulin-dependent diabetes mellitus in nonobese diabetic mice. Biochem. Biophys. Res. Commun. 286, 1051-1058 (2001).