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Immunoendocrinology: Scientific and Clinical Aspects pp 199–213Cite as

Immunopathogenesis of the NOD Mouse

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Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The NOD mouse model of type 1A (immune-mediated) diabetes and genetic derivatives of this strain are probably the most extensively studied autoimmune animal models (1–4  ). NOD mice spontaneously develop insulitis. This is followed in the great majority of female mice by sufficient beta-cell destruction to result in overt diabetes and approximately 50% of male mice develop diabetes. Insulitis develops between 4 and 8 weeks and over a prolonged period of time increasing numbers of mice develop severe hyperglycemia. In addition, the mice develop sialitis and other autoimmune disorders, such as thyroiditis, retinitis, and autoimmune neuropathy, depending upon the genetic backgrounds (5–7  ). Multiple derivatives of the NOD model (congenic strains of mice with specific mutations and transgenes) are available from repositories at the Jackson Laboratories and Taconic and from individual investigators. There is no doubt that type 1A diabetes is the result of T cell-mediated destruction of beta cells with genetic mutations and therapies that eliminate (e.g., Rag and SCID mutations) T cells preventing disease and ability to transfer the disease with autoreactive T cells.

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References

  1. Yang Y, Santamaria P. Lessons on autoimmune diabetes from animal models. Clin Sci (Lond). 2006; 110:627–639.

    Article  CAS  Google Scholar 

  2. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol. 2005; 23:447–485.

    Article  PubMed  CAS  Google Scholar 

  3. Chatenoud L, Bach JF. Regulatory T cells in the control of autoimmune diabetes: the case of the NOD mouse. Int Rev Immunol. 2005; 24:247–267.

    Article  PubMed  CAS  Google Scholar 

  4. Shoda LK, Young DL, Ramanujan S, Whiting CC, Atkinson MA, Bluestone JA, Eisenbarth GS, Mathis D, Rossini AA, Campbell SE, Kahn R, Kreuwel HT. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity. 2005; 23:115–126.

    Article  PubMed  CAS  Google Scholar 

  5. Braley-Mullen H, Sharp GC, Medling B, Tang H. Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J Autoimmun. 1999; 12:157–165.

    Article  PubMed  CAS  Google Scholar 

  6. Bour-Jordan H, Thompson HL, Bluestone JA. Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice. J Immunol. 2005; 175:5649–5655.

    PubMed  CAS  Google Scholar 

  7. Salomon B, Rhee L, Bour-Jordan H, Hsin H, Montag A, Soliven B, Arcella J, Girvin AM, Miller SD, Bluestone JA. Development of spontaneous autoimmune peripheral polyneuropathy in b7-2-deficient nod mice. J Exp Med. 2001; 194:677–684.

    Article  PubMed  CAS  Google Scholar 

  8. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol. 2007; 7:622–632.

    Article  PubMed  CAS  Google Scholar 

  9. Roep BO. Are insights gained from NOD mice sufficient to guide clinical translation? Another inconvenient truth. Ann N Y Acad Sci. 2007; 1103:1–10.

    Article  PubMed  CAS  Google Scholar 

  10. Serreze DV, Gaskins HR, Leiter EH. Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. J Immunol. 1993; 150:2534–2543.

    PubMed  CAS  Google Scholar 

  11. Hattori M, Buse JB, Jackson RA, Glimcher L, Dorf ME, Minami M, Makino S, Moriwaki K, Korff M, Kuzuya H, Imura H, Seidman JG, Eisenbarth GS. The NOD mouse: recessive diabetogenic gene within the major histocompatibility complex. Science. 1986; 231:733–735.

    Article  PubMed  CAS  Google Scholar 

  12. Fujisawa T, Ikegami H, Noso S, Yamaji K, Nojima K, Babaya N, Itoi-Babaya M, Hiromine Y, Kobayashi M, Makino S, Ogihara T. MHC-linked susceptibility to type 1 diabetes in the NOD mouse: further localization of Idd16 by subcongenic analysis. Ann N Y Acad Sci. 2006; 1079:118–121.

    Article  PubMed  CAS  Google Scholar 

  13. Todd JA, Acha-Orbea H, Bell JI, Chao N, Fronek Z, Jacob CO, McDermott M, Sinha AA, Timmerman L, Steinman L, McDevitt HO. A molecular basis for MHC class II associated autoimmunity. Science. 1988; 240:1003–1009.

    Article  PubMed  CAS  Google Scholar 

  14. Todd JA, Bell JI, McDevitt HO. A molecular basis for genetic susceptibility to insulin dependent diabetes mellitus. Trends Genet. 1988; 4:129–134.

    Article  PubMed  CAS  Google Scholar 

  15. Corper AL, Stratmann T, Apostolopoulos V, Scott CA, Garcia KC, Kang AS, Wilson IA, Teyton L. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science. 2000; 288:505–511.

    Article  PubMed  CAS  Google Scholar 

  16. Kanagawa O, Shimizu J, Unanue ER. The role of I-Ag7 b chain in peptide binding and antigen recognition by T cells. Int Immunol. 1998; 9:1523–1526.

    Article  Google Scholar 

  17. Suri A, Unanue ER. The murine diabetogenic class II histocompatibility molecule I-A(g7): structural and functional properties and specificity of peptide selection. Adv Immunol. 2005; 88:235–265.

    Article  PubMed  CAS  Google Scholar 

  18. Levisetti MG, Lewis DM, Suri A, Unanue ER. Weak proinsulin peptide-major histocompatibility complexes are targeted in autoimmune diabetes in mice. Diabetes. 2008; 57:1852–1860.

    Article  PubMed  CAS  Google Scholar 

  19. Levisetti MG, Suri A, Petzold SJ, Unanue ER. The insulin-specific T cells of nonobese diabetic mice recognize a weak MHC-binding segment in more than one form. J Immunol. 2007; 178:6051–6057.

    PubMed  CAS  Google Scholar 

  20. Homann D, Eisenbarth GS. An immunologic homunculus for type 1 diabetes. J Clin Invest. 2006; 116:1212–1215.

    Article  PubMed  CAS  Google Scholar 

  21. Moriyama H, Abiru N, Paronen J, Sikora K, Liu E, Miao D, Devendra D, Beilke J, Gianani R, Gill RG, Eisenbarth GS. Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse. Proc Natl Acad Sci U S A. 2003; 100:10376–10381.

    Article  PubMed  CAS  Google Scholar 

  22. Boulard O, Damotte D, Deruytter N, Fluteau G, Carnaud C, Garchon HJ. An interval tightly linked to but distinct from the h2 complex controls both overt diabetes (idd16) and chronic experimental autoimmune thyroiditis (ceat1) in nonobese diabetic mice. Diabetes. 2002; 51:2141–2147.

    Article  PubMed  CAS  Google Scholar 

  23. Aoki CA, Borchers AT, Ridgway WM, Keen CL, Ansari AA, Gershwin ME. NOD mice and autoimmunity. Autoimmun Rev. 2005; 4:373–379.

    Article  PubMed  CAS  Google Scholar 

  24. Chen YG, Silveira PA, Osborne MA, Chapman HD, Serreze DV. Cellular expression requirements for inhibition of type 1 diabetes by a dominantly protective major histocompatibility complex haplotype. Diabetes. 2007; 56:424–430.

    Article  PubMed  CAS  Google Scholar 

  25. Reifsnyder PC, Li R, Silveira PA, Churchill G, Serreze DV, Leiter EH. Conditioning the genome identifies additional diabetes resistance loci in Type I diabetes resistant NOR/Lt mice. Genes Immun. 2005; 6:528–538.

    Article  PubMed  CAS  Google Scholar 

  26. Inoue K, Ikegami H, Fujisawa T, Noso S, Nojima K, Babaya N, Itoi-Babaya M, Makimo S, Ogihara T. Allelic variation in class I K gene as candidate for a second component of MHC-linked susceptibility to type 1 diabetes in non-obese diabetic mice. Diabetologia. 2004; 47:739–747.

    Article  PubMed  CAS  Google Scholar 

  27. Leiter EH. Nonobese diabetic mice and the genetics of diabetes susceptibility. Curr Diab Rep. 2005; 5:141–148.

    Article  PubMed  CAS  Google Scholar 

  28. Pomerleau DP, Bagley RJ, Serreze DV, Mathews CE, Leiter EH. Major histocompatibility complex-linked diabetes susceptibility in NOD/Lt mice: subcongenic analysis localizes a component of Idd16 at the H2-D end of the diabetogenic H2(g7) complex. Diabetes. 2005; 54:1603–1606.

    Article  PubMed  CAS  Google Scholar 

  29. Hamilton-Williams EE, Serreze DV, Charlton B, Johnson EA, Marron MP, Mullbacher A, Slattery RM. Transgenic rescue implicates beta2-microglobulin as a diabetes susceptibility gene in nonobese diabetic (NOD) mice. Proc Natl Acad Sci U S A. 2001; 98:11533–11538.

    Article  PubMed  CAS  Google Scholar 

  30. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, Gonzalez-Munoz A, Clark J, Veijola R, Cubbon R, Chen SL, Rosa R, Cumiskey AM, Serreze DV, Gregory S, Rogers J, Lyons PA, Healy B, Smink LJ, Todd JA, Peterson LB, Wicker LS, Santamaria P. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet. 2007; 39(3):329–337.

    Article  PubMed  CAS  Google Scholar 

  31. Bluestone JA. Is CTLA-4 a master switch for peripheral T cell tolerance? J Immunol. 1997; 158:1989–1993.

    PubMed  CAS  Google Scholar 

  32. Hunter K, Rainbow D, Plagnol V, Todd JA, Peterson LB, Wicker LS. Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes. J Immunol. 2007; 179:8341–8349.

    PubMed  CAS  Google Scholar 

  33. Lenschow DJ, Herold KC, Rhee L, Patel B, Koons A, Qin HY, Fuchs E, Singh B, Thompson CB, Bluestone JA. CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity. 1996; 5:285–293.

    Article  PubMed  CAS  Google Scholar 

  34. Bergman ML, Cilio CM, Penha-Goncalves C, Lamhamedi-Cherradi SE, Lofgren A, Colucci F, Lejon K, Garchon HJ, Holmberg D. CTLA-4−/− mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice. J Autoimmun. 2001; 16:105–113.

    Article  PubMed  CAS  Google Scholar 

  35. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse,CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskivina V, Nikolov I, O’donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop TD, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Matthew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop MG, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hilder SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdo’ttir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Brown MA, Compston A, Farrall M, Hall AS, Hattersley AT, Hill AV, Parkes M, Pembrey M, Stratton MR, Mitchell SL, Newby PR, Brand OJ, Carr-Smith J, Pearce SH, McGinnis R, Keniry A, Deloukas P, Reveille JD, Zhou X, Sims AM, Dowling A, Taylor J, Doan T, Davis JC, Savage L, Ward MM, Learch TL, Weisman MH, Brown M. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007; 39:1329–1337.

    Article  PubMed  CAS  Google Scholar 

  36. Barratt BJ, Payne F, Lowe CE, Hermann R, Healy BC, Harold D, Concannon P, Gharani N, McCarthy MI, Olavesen MG, McCormack R, Guja C, Ionescu-Tirgoviste C, Undlien DE, Ronningen KS, Gillespie KM, Tuomilehto-Wolf E, Tuomilehto J, Bennett ST, Clayton DG, Cordell HJ, Todd JA. Remapping the Insulin Gene/IDDM2 Locus in Type 1 Diabetes. Diabetes. 2004; 53:1884–1889.

    Article  PubMed  CAS  Google Scholar 

  37. Thebault-Baumont K, Dubois-LaForgue D, Krief P, Briand JP, Halbout P, Vallon-Geoffroy K, Morin J, Laloux V, Lehuen A, Carel JC, Jami J, Muller S, Boitard C. Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice. J Clin Invest. 2003; 111:851–857.

    PubMed  CAS  Google Scholar 

  38. Pugliese A, Zeller M, Fernandez A, Zalcberg LJ, Bartlett RJ, Ricordi C, Pietropaolo M, Eisenbarth GS, Bennett ST, Patel DD: The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type I diabetes. Nat Genet. 1997; 15:293–297.

    Article  PubMed  CAS  Google Scholar 

  39. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, McKenna S, Mobraaten L, Rajan TV, Greiner DL. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995; 154:180–191.

    PubMed  CAS  Google Scholar 

  40. Laloux V, Beaudoin L, Jeske D, Carnaud C, Lehuen A. NK T cell-induced protection against diabetes in V alpha 14-J alpha 281 transgenic nonobese diabetic mice is associated with a Th2 shift circumscribed regionally to the islets and functionally to islet autoantigen. J Immunol. 2001; 166:3749–3756.

    PubMed  CAS  Google Scholar 

  41. Peng RH, Paek E, Xia CQ, Tennyson N, Clare-Salzler MJ. Heightened interferon-alpha/beta response causes myeloid cell dysfunction and promotes T1D pathogenesis in NOD mice. Ann N Y Acad Sci. 2006; 1079:99–102.

    Article  PubMed  CAS  Google Scholar 

  42. Nikolic T, Bunk M, Drexhage HA, Leenen PJ. Bone marrow precursors of nonobese diabetic mice develop into defective macrophage-like dendritic cells in vitro. J Immunol. 2004; 173:4342–4351.

    PubMed  CAS  Google Scholar 

  43. Ogasawara K, Hamerman JA, Hsin H, Chikuma S, Bour-Jordan H, Chen T, Pertel T, Carnaud C, Bluestone JA, Lanier LL. Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity. 2003; 18:41–51.

    Article  PubMed  CAS  Google Scholar 

  44. 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. 2001; 166:2404–2411.

    PubMed  CAS  Google Scholar 

  45. Poulton LD, Smyth MJ, Hawke CG, Silveira P, Shepherd D, Naidenko OV, Godfrey DI, Baxter AG. Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice. Int Immunol. 2001; 13:887–896.

    Article  PubMed  CAS  Google Scholar 

  46. Poirot L, Benoist C, Mathis D. Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity. Proc Natl Acad Sci U S A. 2004; 101:8102–8107.

    Article  PubMed  CAS  Google Scholar 

  47. Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998; 161:3912–3918.

    PubMed  CAS  Google Scholar 

  48. Greeley SA, Katsumata M, Yu L, Eisenbarth GS, Moore DJ, Goodarzi H, Barker CF, Naji A, Noorchashm H. Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Med. 2002; 8:399–402.

    Article  PubMed  CAS  Google Scholar 

  49. Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, Shlomchik MJ, Wen L. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest. 2007; 117:3857–3867.

    Article  PubMed  CAS  Google Scholar 

  50. Kobayashi M, Jasinski J, Liu E, Li M, Miao D, Zhang L, Yu L, Nakayama M, Eisenbarth GS. Conserved T cell receptor alpha-chain induces insulin autoantibodies. Proc Natl Acad Sci U S A. 2008; 105:10090–10094.

    Article  PubMed  CAS  Google Scholar 

  51. Abiru N, Yu L, Miao D, Maniatis AK, Liu E, Moriyama H, Eisenbarth GS. Transient insulin autoantibody expression independent of development of diabetes: comparison of NOD and NOR strains. J Autoimmun. 2001; 17:1–6.

    Article  PubMed  CAS  Google Scholar 

  52. DiLorenzo TP, Serreze DV. The good turned ugly: immunopathogenic basis for diabetogenic CD8+ T cells in NOD mice. Immunol Rev. 2005; 204:250–263.

    Article  PubMed  CAS  Google Scholar 

  53. DiLorenzo TP, Lieberman SM, Takaki T, Honda S, Chapman HD, Santamaria P, Serreze DV, Nathenson SG. During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificities. Clin Immunol. 2002; 105:332–341.

    Article  PubMed  CAS  Google Scholar 

  54. Lieberman SM, Takaki T, Han B, Santamaria P, Serreze DV, DiLorenzo TP. Individual nonobese diabetic mice exhibit unique patterns of CD8+ T cell reactivity to three islet antigens, including the newly identified widely expressed dystrophia myotonica kinase. J Immunol. 2004; 173:6727–6734.

    PubMed  CAS  Google Scholar 

  55. Lieberman SM, DiLorenzo TP. A comprehensive guide to antibody and T-cell responses in type 1 diabetes. Tissue Antigens. 2003; 62:359–377.

    Article  PubMed  CAS  Google Scholar 

  56. Han B, Serra P, Yamanouchi J, Amrani A, Elliott JF, Dickie P, DiLorenzo TP, Santamaria P. Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes. J Clin Invest. 2005; 115:1879–1887.

    Article  PubMed  CAS  Google Scholar 

  57. Kim SK, Tarbell KV, Sanna M, Vadeboncoeur M, Warganich T, Lee M, Davis M, McDevitt HO. Prevention of type I diabetes transfer by glutamic acid decarboxylase 65 peptide 206-220-specific T cells. Proc Natl Acad Sci U S A. 2004; 101:14204–14209.

    Article  PubMed  CAS  Google Scholar 

  58. Gebe JA, Unrath KA, Yue BB, Miyake T, Falk BA, Nepom GT. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice. J Autoimmun. 2008; 30:197–206.

    Article  PubMed  CAS  Google Scholar 

  59. Krishnamurthy B, Dudek NL, McKenzie MD, Purcell AW, Brooks AG, Gellert S, Colman PG, Harrison LC, Lew AM, Thomas HE, Kay TW. Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest. 2006; 116:3258–3265.

    Article  PubMed  CAS  Google Scholar 

  60. West J, Logan RF, Card TR, Smith C, Hubbard R. Fracture risk in people with celiac disease: a population-based cohort study. Gastroenterology. 2003; 125:429–436.

    Article  PubMed  Google Scholar 

  61. Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005; 435:220–223.

    Article  PubMed  CAS  Google Scholar 

  62. Nakayama M, Beilke JN, Jasinski JM, Kobayashi M, Miao D, Li M, Coulombe MG, Liu E, Elliott JF, Gill RG, Eisenbarth GS. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest. 2007; 117:1835–1843.

    Article  PubMed  CAS  Google Scholar 

  63. Burton AR, Vincent E, Arnold PY, Lennon GP, Smeltzer M, Li CS, Haskins K, Hutton J, Tisch RM, Sercarz EE, Santamaria P, Workman CJ, Vignali DA. On the pathogenicity of autoantigen-specific T-cell receptors. Diabetes. 2008; 57:1321–1330.

    Article  PubMed  CAS  Google Scholar 

  64. Hansson T, Dahlbom I, Rogberg S, Nyberg BI, Dahlstrom J, Anneren G, Klareskog L, Dannaeus A. Antitissue transglutaminase and antithyroid autoantibodies in children with Down syndrome and celiac disease. J Pediatr Gastroenterol Nutr. 2005; 40:170–174.

    Article  PubMed  CAS  Google Scholar 

  65. Hoglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med. 1999; 189:331–339.

    Article  PubMed  CAS  Google Scholar 

  66. Tritt M, Sgouroudis E, d’Hennezel E, Albanese A, Piccirillo CA. Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune ­diabetes. 2008; Diabetes 57:113–123.

    Article  PubMed  CAS  Google Scholar 

  67. Hutchings PR, Cooke A. The transfer of autoimmune diabetes in NOD mice can be inhibited or accelerated by distinct cell populations present in normal splenocytes taken from young males. J Autoimmun. 1990; 3:175–185.

    Article  PubMed  CAS  Google Scholar 

  68. Lepault F, Gagnerault MC. Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic mice. J Immunol. 2000; 164:240–247.

    PubMed  CAS  Google Scholar 

  69. Fontenot JD, Rudensky AY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005; 6:331–337.

    Article  PubMed  CAS  Google Scholar 

  70. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4:330–336.

    Article  PubMed  CAS  Google Scholar 

  71. Chen Z, Herman AE, Matos M, Mathis D, Benoist C. Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J Exp Med. 2005; 202:1387–1397.

    Article  PubMed  CAS  Google Scholar 

  72. Masteller EL, Warner MR, Tang Q, Tarbell KV, McDevitt H, Bluestone JA. Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J Immunol. 2005; 175:3053–3059.

    PubMed  CAS  Google Scholar 

  73. Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J, Masteller EL, McDevitt H, Bonyhadi M, Bluestone JA. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 2004; 199:1455–1465.

    Article  PubMed  CAS  Google Scholar 

  74. Mukherjee R, Chaturvedi P, Qin HY, Singh B. CD4+CD25+ regulatory T cells generated in response to insulin B:9-23 peptide prevent adoptive transfer of diabetes by diabetogenic T cells. J Autoimmun. 2003; 21:221–237.

    Article  PubMed  CAS  Google Scholar 

  75. Billiard F, Litvinova E, Saadoun D, Djelti F, Klatzmann D, Cohen JL, Marodon G, Salomon BL. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J Immunol. 2006; 177:2167–2174.

    PubMed  CAS  Google Scholar 

  76. King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, Atkinson M, Wasserfall C, Herold K, Mordes JP, Rossini AA, Greiner DL. Development of new-generation HU-PBMC-NOD/SCID mice to study human islet alloreactivity. Ann N Y Acad Sci. 2007; 1103:90–93.

    Article  PubMed  CAS  Google Scholar 

  77. Pearson T, Greiner DL, Shultz LD. Creation of “humanized” mice to study human immunity. Curr Protoc Immunol 2008 Chapter 15:Unit 15.21.

    Google Scholar 

  78. Wegmann DR, Norbury-Glaser M, Daniel D. Insulin-specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD mice. Eur J Immunol. 1994; 24:1853–1857.

    Article  PubMed  CAS  Google Scholar 

  79. Simone E, Daniel D, Schloot N, Gottlieb P, Babu S, Kawasaki E, Wegmann D, Eisenbarth GS. T cell receptor restriction of diabetogenic autoimmune NOD T cells. Proc Natl Acad Sci USA. 1997; 94:2518–2521.

    Article  PubMed  CAS  Google Scholar 

  80. Ochs HD, Gambineri E, Torgerson TR. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol Res. 2007; 38:112–121.

    Article  PubMed  CAS  Google Scholar 

  81. Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson NO, Aman J, Ortqvist E, Zerhouni P, Casas R. GAD Treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med. 2008; 359(18):1909–1920.

    Article  PubMed  CAS  Google Scholar 

  82. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3{gamma}1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005; 54:1763–1769.

    Article  PubMed  CAS  Google Scholar 

  83. Bresson D, Togher L, Rodrigo E, Chen YL, Bluestone JA, Herold KC, von Herrath M. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. Journal of Clinical Investigation. 2006; 116:1371–1381.

    Article  PubMed  CAS  Google Scholar 

  84. Roep BO, Atkinson M, von Herrath M. Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes. Nat Rev Immunol. 2004; 4:989–997.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA

    Li Zhang

  2. Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Aurora, CO, USA

    George S. Eisenbarth

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  1. Li Zhang
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  2. George S. Eisenbarth
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  1. Health Sciences Center, Children's Hospital, University of Colorado, East 9th Avenue 4200, Denver, 80262, Colorado, USA

    George S. Eisenbarth

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Zhang, L., Eisenbarth, G.S. (2011). Immunopathogenesis of the NOD Mouse. In: Eisenbarth, G. (eds) Immunoendocrinology: Scientific and Clinical Aspects. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-478-4_12

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  • DOI: https://doi.org/10.1007/978-1-60327-478-4_12

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