The role of islet antigen presenting cells and the presentation of insulin in the initiation of autoimmune diabetes in the NOD mouse

Immunological Reviews

Volumn 272, Issue 1, 2016, Pages 183-201

  Unanue, Emil R ^a   Ferris, Stephen T ^a   Carrero, Javier A ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

autoimmune diabetes; CD103+ dendritic cells; insulin autoreactivity; islets of Langerhans; macrophages

Indexed keywords

ANTIGEN; C PEPTIDE; CD103 ANTIGEN; CD11B ANTIGEN; CD206 ANTIGEN; CD301 ANTIGEN; CD64 ANTIGEN; CD68 ANTIGEN; CD8ALPHA ANTIGEN; CHEMOKINE RECEPTOR CX3CR1; GLUTAMATE DECARBOXYLASE; GLYCOPROTEIN P 15095; HLA DQ2 ANTIGEN; HLA DQ8 ANTIGEN; INSULIN; INTERFERON; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PROINSULIN; UNCLASSIFIED DRUG;

ANTIGEN PRESENTING CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DENDRITIC CELL; GENE EXPRESSION; HUMAN; IMMUNOREACTIVITY; MACROPHAGE; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REVIEW; VARIABLE NUMBER OF TANDEM REPEAT; VASCULAR ENDOTHELIUM;

EID: 84975518469     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12430     Document Type: Review

References (95)

1. Mohan JF, Levisetti MG, Calderon B, Herzog JW, Petzold SJ, Unanue ER. Unique autoreactive T cells recognize insulin peptides generated within the islets of Langerhans in autoimmune diabetes. Nat Immunol 2010;11:350–354.
2. Mohan JF, Petzold SJ, Unanue ER. Register shifting of an autoimmune insulin peptide-MHC II complex allows for the escape of diabetogenic T cells from negative selection. J Exp Med 2011;208:2375–2383.
3. Ferris ST, Carrero JA, Mohan JF, Calderon B, Murphy KM, Unanue ER. A minor subset of Batf3-dependent antigen presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes. Immunity 2014;41:657–669.
4. Carrero JA, Calderon B, Towfic F, Artyomov MN, Unanue ER. Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD mouse. PLoS ONE 2013;8:e59701.
5. Calderon B, Carrero JA, Miller MJ, Unanue ER. Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans. Proc Natl Acad Sci USA 2011;108:1561–1566.
6. Vomund AN, et al. Beta cell transfer vesicles containing insulin to phagocytes for presentation to T cells. Proc Natl Acad Sci USA 2015;112:5496–5502.
7. Kikutani H, Makino S. The murine autoimmune diabetes model: NOD and related strains. Adv Immunol 1992;51:285–322.
8. Wen L, et al. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 2008;455:1109–1113.
9. Hattori M, et al. The NOD mouse: recessive diabetogenic gene in the major histocompatibility complex. Science 1986;231:733–735.
10. Acha-Orbea H, McDevitt HO. The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. Proc Natl Acad Sci USA 1987;84:2435–2439.
11. Lund T, et al. Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-A beta-chain or normal I-E alpha-chain. Nature 1990;345:727–729.
12. Todd JA, Bell JI, McDevitt HO. HLA-DQ β gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 1987;329:599–604.
13. Corper AL, et al. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science 2000;288:505–511.
14. Latek RR, et al. Structural basis of peptide binding and presentation by the type 1 diabetes-associated MHC class II molecule of NOD mice. Immunity 2000;12:699–710.
15. Lee KH, Wucherpfenning KW, Wiley DC. Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. Nat Immunol 2001;2:501–507.
16. g7 molecules show common sequence specificity. J Clin Invest 2005;115:2268–2276.
17. Chang KY, Unanue ER. Prediction of HLA-DQ8β cell peptidome using a computational program and its relationship to autoreactive T cells. Int Immunol 2009;21:705–713.
18. Godkin A, et al. Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2). Int Immunol 1997;9:905–911.
19. g7 molecule are unique and determined by the amino acid changes in the P9 pocket. J Immunol 2002;168:1235–1243.
20. Unanue ER. Antigen presentation in the autoimmune diabetes of the NOD mouse. Annu Rev Immunol 2014;32:579–608.
21. Wegmann DR, Eisenbarth GS. It's insulin. J Autoimmun 2000;15:286–291.
22. Zhang L, Nakayama M, Eisenbarth GS. Insulin as an autoantigen in NOD/human diabetes. Curr Opin Immunol 2008;20:111–118.
23. Brezar V, Carel JC, Boitard C, Mallone R. Beyond the hormone: insulin as an autoimmune target in type 1 diabetes. Endocr Rev 2011;32:623–669.
24. Verge CF, et al. Prediction of type I diabetes mellitus in first degree relatives using a combination of insulin, glutamic acid decarboxylase and ICA512bdc/IA-2 autoantibodies. Diabetes 1996;45:926–933.
25. Pietropaolo M, Towns R, Eisenbarth GS. Humoral autoimmunity in type 1 diabetes: prediction, significance, and detection of distinct disease subtypes. Cold Spring Harb Perspect Med 2012;2:1–18.
26. Ziegler AG, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309:2473–2479.
27. French MB, et al. Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice. Diabetes 1997;46:34–39.
28. Jaeckel E, Lipes MA, von Boehmer H. Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes. Nat Immunol 2004;5:1028–1035.
29. Klein L, Hinterberger M, Wirnsberger G, Kyewski B. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol 2009;9:833–844.
30. Thebault-Baumont K, et al. Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice. J Clin Invest 2003;111:851–857.
31. Moriyama H, et al. Evidence for a primary islet autoantigen (preproinsulin1) for insulitis and diabetes in the nonobese diabetic mouse. Proc Natl Acad Sci USA 2003;100:10376–10381.
32. Bell GI, Horita S, Karam JH. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 1984;33:176–183.
33. Lucassen AM, et al. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet 1993;4:305–310.
34. Pugliese A, et al. 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 1 diabetes. Nat Genet 1997;15:293–297.
35. Husebye ES, Anderson MS. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis. Immunity 2010;32:479–487.
36. 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.
37. Wegmann DR, Gill RG, Norbury-Glaser M, Schloot N, Daniel D. Analysis of the spontaneous T cell response to insulin in NOD mice. J Autoimmun 1994;7:833–843.
38. Daniel D, Gill RG, Schloot N, Wegmann D. Epitope specificity, cytokine production profile and diabetogenic activity of insulin-specific T cell clones isolated from NOD mice. Eur J Immunol 1995;25:1056–1062.
39. Heath VL, Hutchings P, Fowell DJ, Cooke A, Mason DW. Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducting epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes. Diabetes 1999;48:2157–2165.
40. Halbout P, Briand J-P, Becourt C, Muller S, Boitard C. T cell response to preproinsulin I and II in the nonobese diabetic mouse. J Immunol 2002;169:2436–2443.
41. Stadinski BD, Zhang L, Crawford F, Marrack P, Eisenbarth GS, Kappler JW. Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. Proc Natl Acad Sci USA 2010;107:10978–10983.
42. Haskins K, Portas M, Bradley B, Wegmann D, Lafferty K. T-lymphocyte clone specific for pancreatic islet antigen. Diabetes 1988;37:1444–1448.
43. Haskins K, Portas M, Bergman B, Lafferty K, Bradley B. Pancreatic islet-specific T-cell clones from nonobese diabetic mice. Proc Natl Acad Sci USA 1989;86:8000–8004.
44. Mohan JF, Unanue ER. Unconventional recognition of peptides by T cells and the implications for autoimmunity. Nat Rev Immunol 2012;12:721–728.
45. Levisetti MG, Suri A, Petzold SJ, Unanue ER. The insulin-specific T cells of NOD mice recognize a weak MHC-binding segment in more than one register. J Immunol 2007;178:6051–6057.
46. + T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes. J Exp Med 2013;210:2403–2414.
47. Yoshida K, Corper AL, Herro R, Jabri B, Wilson IA, Teyton L. The diabetogenic mouse MHC class II moleculeI-Ag7 is endowed with a switch that modulates TCR affinity. J Clin Invest 2010;120:1578–1590.
48. Unanue ER, Turk V, Neefjes J. Variations in MHC class II antigen processing and presentation in health and disease. Ann Rev Immunol 2016, (in press).
49. Pu Z, Carrero JA, Unanue ER. Distinct recognition by two subsets of T cells of an MHC class II–peptide complex. PNAS 2002;99:8844–8849.
50. Pu Z, Lovitch SB, Bikoff EK, Unanue ER. T cells distinguish MHC-peptide complexes formed in separate vesicles and edited by H2-DM. Immunity 2004;20:467–476.
51. Viner NJ, Nelson CA, Deck B, Unanue ER. Complexes generated by the binding of free peptides to class II MHC molecules are antigenically diverse compared with those generated by intracellular processing. J. Immunol 1996;156:2365–2368.
52. Peterson DA, DiPaolo RJ, Kanagawa O, Unanue ER. Quantitative analysis of the T cell repertoire that escapes negative selection. Immunity 1999;11:453–462.
53. Landsteiner K. The specificity of serological reactions. New York: Dover Publications, 1962.
54. Weigle WO. The induction of autoimmunity in rabbits following injection of heterologous or altered homologous thyroglobulin. J Exp Med 1965;121:289–308.
55. McCluskey RT, Miller F, Benacerraf B. Sensitization to denatured autologous globulin. J Exp Med 1962;115:253–273.
56. Rosenthal AS, Barcinski MA, Blake JT. Determinant selection is a macrophage dependent immune response gene function. Nature 1977;267:156–158.
57. Thomas JW, George-Gattner H, Danho W. T cells recognize both conformational and cryptic determinants on the insulin molecule. Eur J Immunol 1989;19:557–558.
58. Nakayama M, et al. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 2005;435:220–223.
59. Nakayama M, Babaya N, Miao D, Sikora K, Elliott JF, Eisenbarth GS. Thymic expression of mutated B16: a preproinsulin messenger RNA does not reverse acceleration of NOD diabetes associated with insulin 2 (thymic expression insulin) knockout. J Autoimmun 2005;25:193–198.
60. Nakayama M, et al. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest 2007;117:1835–1843.
61. Gagnerault MC, Luan JJ, Lotton C, Lepault F. Pancreatic lymph nodes are required for priming of β cell reactive T cells in NOD mice. J Exp Med 2001;196:369–377.
62. Levisetti MG, Suri A, Frederick K, Unanue ER. Absence of lymph nodes in NOD mice treated with lymphotoxin-β receptor immunoglobulin protects from diabetes. Diabetes 2004;53:3115–3119.
63. Halban PA, Wollheim CB. Intracellular degradation of insulin stores by rat pancreatic islets in vitro. An alternative pathway for homeostasis of pancreatic insulin content. J Biol Chem 1980;255:6003–6006.
64. Orci L, et al. Insulin, not C-peptide (proinsulin), is present in crinophagic bodies of the pancreatic B-cell. J Cell Biol 1984;98:222–228.
65. Arvan P, Halban PA. Sorting ourselves out: seeking consensus on trafficking in the beta-cell. Traffic 2004;5:53–61.
66. Unanue ER, Askonas BA. Persistence of immunogenicity of antigen after uptake by macrophages. J Exp Med 1968;127:915–926.
67. Unanue ER, Askonas BA. The immune response of mice to antigen in macrophages. Immunol 1968;15:287–296.
68. Unanue ER, Cerottini J-C, Bedford M. Persistence of antigen on the surface of macrophages. Nature 1969;222:1193–1195.
69. Ziegler K, Unanue ER. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to lymphocytes. J Immunol 1981;127:1869–1875.
70. Ziegler K, Unanue ER. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci USA 1982;78:175–178.
71. Rosenthal AS, Shevach EM. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med 1973;138:1194–1212.
72. Shevach EM, Rosenthal AS. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med 1973;138:1213–1229.
73. Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol 2008;181:5829–5835.
74. Calderon B, et al. The pancreas anatomy conditions the origin and properties of resident macrophages. J Exp Med 2015;212:1497–1512.
75. Asano K, et al. D169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 2011;34:85–95.
76. + dendritic cells in the generation of cytotoxic T cells. Proc Natl Acad Sci USA 2010;107:216–221.
77. Nikbakht N, Shen S, Manser T. Macrophages are required for localization of antigen-activated B cells to the follicular perimeter and the subsequent germinal center response. J Immunol 2013;190:4923–4927.
78. Calderon B, Suri A, Miller M, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci USA 2008;105:6121–6126.
79. Calderon B, Unanue ER. Antigen presentation events in autoimmune diabetes. Curr Opin Immunol 2012;24:119–128.
80. Calderon B, Carrero JA, Unanue ER. The central role of antigen presentation in islets of Langerhans in autoimmune diabetes. Curr Opin Immunol 2014;26C:32–40.
81. Melli K, et al. Amplification of autoimmune response through induction of dendritic cell maturation in inflamed tissues. J Immunol 2009;182:2590–2600.
82. Tang Q, et al. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 2006;7:83–92.
83. Murray PJ, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41:14–20.
84. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013;496:445–455.
85. op macrophage-deficient mice. J Leukoc Biol 2004;76:359–367.
86. Li Q, Xu B, Michie SA, Rubins KH, Schreiber RD, McDevitt HO. Interfon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci USA 2008;105:12439–12444.
87. Quah HS, et al. Deficiency in type I interferon signaling prevents the early interferon-induced gene signature in pancreatic islets but not type 1 diabetes in NOD mice. Diabetes 2014;63:1032–1040.
88. Serreze DV, Post CM, Chapman HD, Johnson EA, Lu B, Rothman PB. Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes 2000;49:2007–2011.
89. Kanagawa O, Xu G, Tevaarwerk A, Vaupel BA. Protection of nonobese diabetic mice from diabetes by gene(s) closely linked to IFN-gamma receptor loci. J Immunol 2000;164:a3919–a3923.
90. + dendritic cells in cytotoxic T cell immunity. Science 2008;322:1097–1100.
91. + conventional dendritic cells. J Exp Med 2010;207:823–836.
92. Grajales-Reyes GE, et al. Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor. Nat Immunol 2015;16:708–717.
93. Calderon B, Carrero JA, Miller MJ, Unanue ER. Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response. Proc Natl Acad Sci USA 2011;108:567–572.
94. Hasegawa Y, et al. Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb. Int Immunol 1994;6:831–838.
95. Tsukamoto K, et al. Administration of monoclonal antibodies against vascular cell adhesion molecule-1/very late antigen-4 abrogates predisposing autoimmune diabetes in NOD mice. Cell Immunol 1995;165:193–201.