Abstract
The first line of treatment developed for T1D was insulin. Over the last century, several new approaches to treat T1D have been adopted (Fig. 4.1), but insulin delivery still remains the main stream of treatment. The new strategies to treat T1D include replacement of β-cell via transplantation or regeneration, but are still in their infancy. Another vibrant approach in T1D immunotherapy involves compensating for the lost pancreatic β-cells and restoration of immunological tolerance by islet like cells derived from stem cells. The major benefit associated with these intervention strategies is the ease of patient identification and efficacy evaluation within a much shorter duration. Earlier reports on NOD mice had provided the basis for antigenic and non-antigenic preventive strategies to treat T1D, but a number of clinical trials have been completed with limited success so far. An ideal intervention for T1D would require an entity to halt autoimmune response along with an additional element to enhance β-cell function or expedite its regeneration. As such, combination therapy is believed to lead the treatment of T1D in the time to come.
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References
Ablamunits V, Henegariu O et al (2012) Synergistic reversal of type 1 diabetes in NOD mice with anti-CD2 and interleukin-1 blockade: evidence of improved immune regulation. Diabetes 61(1):145–154
Abramowicz D, Schandene L et al (1989) Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 47(4):606–608
Abulafia-Lapid R, Elias D et al (1999) T cell proliferative responses of type 1 diabetes patients and healthy individuals to human hsp60 and its peptides. J Autoimmun 12(2):121–129
Agardh CD, Lynch K et al (2009) GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes. Diabetologia 52(7):1363–1368
Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822
Alexander AM, Crawford M et al (2002) Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. Diabetes 51(2):356–365
Alleva DG, Maki RA et al (2006) Immunomodulation in type 1 diabetes by NBI-6024, an altered peptide ligand of the insulin B epitope. Scand J Immunol 63(1):59–69
Anderton S, Burkhart C et al (1999) Mechanisms of central and peripehral T-cell tolerance: lessons from experimental models of multiple sclerosis. Immunolo Rev 169(1):123–137
Anderton SM, van der Zee R et al (1993) Inflammation activates self hsp60-specific T cells. Eur J Immunol 23(1):33–38
Arima T, Rehman A et al (1996) Inhibition by CTLA4Ig of experimental allergic encephalomyelitis. J Immunol 156(12):4916–4924
Augello A, Tasso R et al (2005) Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 35(5):1482–1490
Baekkeskov S, Aanstoot HJ et al (1990) Identification of the 64 K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347(6289):151–156
Baekkeskov S, Nielsen JH et al (1982) Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 298(5870):167–169
Banting FG, Best CH (1922) The internal secretion of the pancreas. J Lab Clin Med 7:251–266
Barker J, McFann K et al (2007) Effect of oral insulin on insulin autoantibody levels in the diabetes prevention trial type 1 oral insulin study. Diabetologia 50(8):1603–1606
Baumann B, Salem HH et al (2012) Anti-inflammatory therapy in type 1 diabetes. Curr Diab Rep 12(5):499–509
Beattie GM, Otonkoski T et al (1997) Functional beta-cell mass after transplantation of human fetal pancreatic cells: diiferentiation or proliferation? Diabetes 46(2):244–248
Belghith M, Bluestone JA et al (2003) TGF-beta dependent mechansims mediate restoration of self-tolerance induced by antibodies CD3 in over autoimmune diabetes. Nat Med 9(9):1202–1208
Ben-Ami E, Berrih-Aknin S et al (2011) Mesenchymal stem cells as an immunomodulatory therapeutic strategy for Autoimmune Diseases. Autoimmun Rev 10(7):410–415
Bielekova B, Howard T et al (2009) Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 66(4):483–489
Bluestone JA, Tang Q (2004) Therapeutic vaccination using CD4 + CD25 + antigen-specific regulatory T cells. Proc Natl Acad Sci USA 101(Suppl 2):14622–14626
Boettler T, von Herrath M (2010) Immunotherapy of type 1 diabetes - How to rationally prioritize combination therapies in T1D. Int Immunopharmacol 10:1491–1495
Bonifaz LC, Bonnyay DP et al (2004) In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 199(6):815–824
Brand SJ, Tagerud S et al (2002) Pharmacological treatment of chronic diabetes by stimulating pancreatic beta-cell regeneration with systemic co-administration of EGF and gastrin. Pharmacol Toxicol 91(6):414–420
Brusko TM (2009) Mesenchymal stem cells: a potential border patrol for transplanted islets? Diabetes 58(8):1728–1729
Bresson D, Togher L et al (2006) Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest 116(5):1371–1381
Bresson D, von Herrath M (2007) Moving towards efficient therapies in type 1 diabetes: to combine or not to combine? Autoimmun Rev 6(5):315–322
Bresson D, von Herrath M (2009) Immunotherapy for the prevention and treatment of type 1 diabetes. Diabetes Care 32(10):1753–1768
Bresson D, von Herrath M (2011) Anti-thymoglobulin (ATG) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model. Clin Exp Immunol 163(3):375–380
Breton M, Farret A et al (2012) Fully integrated artificial pancreas in type 1 diabetes: modular closed-loop glucose control maintains near normoglycemia. Diabetes 61:2230–2237
Brett P, Massimo T et al (2011) Current state of type 1 diabetes immunotherapy: incremental advances, huge leaps, or more of the same? Clin Dev Immunol 2011:432016
Buckingham B, Chase HP et al (2010) Prevention of nocturnal hypoglycemia using predictive alarm algorithm and insulin pump suspension. Diab Care 33:1013–1017
Cao T, Soto A et al (2009) Ex vivo expanded human CD4 + CD25 + Foxp3 + regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD). Cell Immunol 258(1):65–71
Casas R, Hedman M et al (2007) Diabetes 67th annual scientific sessions. 1242
Cash KJ, Clark HA (2010) Nanosensors and nanomaterials for monitoring glucose in diabetes. Trends Mol Med 16(12):584–593
Cernea S, Kidron M et al (2005) Dose-response relationship of an oral insulin spray in six patients with type 1 diabetes: a single-center, randomized, single-blind, 5-way crossover study. Clin Ther 27(10):1562–1570
Chaillous L, Lefčvre H et al (2000) Oral insulin administration and residual ([beta]-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial. Lancet 356(9229):545–549
Chatenoud L (2011) Diabetes: type 1 diabetes mellitus–a door opening to a real therapy? Nat Rev Endocrinol 7(10):564–566
Chatenoud L, Bluestone JA (2007) CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7(8):622–632
Chatenoud L, Ferran C et al (1989) Systemic reaction to the anti–t-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-α. N Eng J Med 320(21):1420–1421
Chatenoud L, Thervet E et al (1994) Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 91(1):123–127
Christen U, Herrath MG (2002) Apoptosis of autoreactive CD8 lymphocytes as a potential mechanism for the abrogation of type 1 diabetes by islet-specific TNF-α expression at a time when the autoimmune process is already ongoing. Ann NY Acad Sci 958(1):166–169
Clark GO, Yochem RL et al (2007) Glucose responsive insulin production from human embryonic germ (EG) cell derivatives. Biochem Biophys Res Commun 356(3):587–593
Damgé C, Reis CP et al (2008) Nanoparticle strategies for the oral delivery of insulin. Expert Opin Drug Deliv 5:45–68
D’Amour KA, Bang AG et al (2006) Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24(11):1392–1401
Dekker CL, Gordon L et al (2008) Dose optimization strategies for vaccines: the role of adjuvants and new technologies, NVAC subcommittee on vaccine development and supply, Washington, DC, HHS: 1–21
Devaskar SU, Giddings SJ et al (1994) Insulin gene expression and insulin synthesis in mammalian neuronal cells. J Biol Chem 269(11):8445–8454
Dor Y, Brown J et al (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429(6987):41-46
d’Hennezel E, Kornete M et al (2010) IL-2 as a therapeutic target for the restoration of Foxp3 + regulatory T cell function in organ-specific autoimmunity: implications in pathophysiology and translation to human disease. J Trans Med 8(1):113
Elias D, Markovits D et al (1990) Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein. Proc Natl Acad Sci USA 87(4):1576–1580
Elias D, Cohen IR (1995) Treatment of autoimmune diabetes and insulitis in NOD mice with heat shock protein 60 peptide p277. Diabetes 44(9):1132–1138
Elleri D, Dunger D et al (2011) Closed-loop insulin delivery for treatment of type 1 diabetes. BMC Med 9:120
Ellis S, Naik RG et al (2008) Use of continuous glucose monitoring in patients with type 1 diabetes. Curr Diab Rev 4:207–217
Engström HA, Johansson R et al (2008) Evaluation of a glucose sensing antibody using weak affinity chrmoatography. Biomed Chromatogr 22:272–277
Ferran C, Dy M et al (1991) Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release. Clin Exp Immunol 86(3):537–543
Feutren G, Papoz L et al (1986) Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet 2(8499):119–124
Fontenot JD, Rasmussen JP et al (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329–341
Fornari TA, Donate PB et al (2011) Development of type 1 diabetes mellitus in nonobese diabetic mice follows changes in thymocyte and peripheral t lymphocyte transcriptional activity. Clin Dev Immunol 2011:158735
Fujinami RS, von Herrath MG et al (2006) Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 19(1):80–94
Gale EA, Bingley PJ et al (2004) European nicotinamide diabetes intervention trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363(9413):925–931
Gambineri E, Torgerson TR et al (2003) 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 15(4):430–435
Giannoukakis N, Phillips B et al (2011) Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diab Care 34(9):2026–2032
Gondek DC, Lu LF et al (2005) Cutting edge: contact-mediated suppression by CD4 + CD25 + regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol 174(4):1783–1786
Gong Z, Pan L et al (2010) Glutamic acid decarboxylase epitope protects against autoimmune diabetes through activation of Th2 immune response and induction of possible regulatory mechanism. Vaccine 28(24):4052–4058
Gordon N, Sagman U et al (2003) Nanomedicine taxonomy. CIHR IRSC:1–32
Gottlieb PA, Quinlan S et al (2010) Failure to preserve β-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new-onset type 1 diabetes. Diab Care 33(4):826–832
Grazia Roncarolo M, Gregori S et al (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev 212(1):28–50
Grinberg-Bleyer Y, Baeyens A et al (2010) IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med 207(9):1871–1878
Grossman WJ, Verbsky JW et al (2004a) Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21(4):589–601
Grossman WJ, Verbsky JW et al (2004b) Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood 104(9):2840–2848
Haller MJ, Atkinson MA, Schatz D (2005) Type 1 diabetes mellitus: etiology, presentation, and management. Pediatr Clin North Am 52:1553–1578
Han S, Donelan W et al (2011) Autoantigen-specific immunotherapy. In: Wagner D (ed) Type 1 diabetes—pathogenesis, genetics and immunotherapy. ISBN: 978-953-307-362-0. doi:10.5772/24479. http://www.intechopen.com/books/type-1-diabetes-pathogenesis-genetics-and-immunotherapy/autoantigen-specific-immunotherapy (InTech)
Hao W, Davis C et al (1999) Plasmapheresis and immunosuppression in stiff-man syndrome with type 1 diabetes: a 2-year study. J Neurol 246(8):731–735
Harrison LC (2012) Insulin-specific vaccination for type 1 diabetes: a step closer? Hum Vaccin Immunother 8(6):834–837
Herold KC, Gitelman S et al (2009) Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol 132:166–173
Herold KC, Bluestone JA et al (1992) Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes 41(3):385–391
Hovorka R (2008) The future of continuous glucose monitoring: closed loop. Curr Diab Rev 4:269–279
Hovorka R (2005) Continuous glucose monitoring and closed-loop systems. Diabet Med 23(1):1–12
Hilsted J, Madsbad S et al (1995) Intranasal insulin therapy: the clinical realities. Diabetologia 38(6):680–684
Harrison LC, Honeyman MC et al (2004) Pancreatic beta-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes. Diab Care 27(10):2348–2355
Harrison LC (2008) Vaccination against self to prevent autoimmune disease: the type 1 diabetes model. Immunol Cell Biol 86(2):139–145
Humar A, Kandaswamy R et al (2000) Decreased surgical risks of pancreas transplantation in the modern era. Ann Surg 231(2):269–275
Huurman VA, van der Meide PE et al (2008) Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes. Clin Exp Immunol 152(3):488–497
Hinke SA (2011) Inverse vaccination with islet autoantigens to halt progression of autoimmune diabetes. Drug Dev Res 72(8):788–804
Jacob CO, Aiso S et al (1990) Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1. Proc Natl Acad Sci USA 87(3):968–972
Jamal A, Lipsett M et al (2005) Morphogenetic plasticity of adult human pancreatic islets of Langerhans. Cell Death Differ 12(7):702–712
Jenner M, Bradish G et al (1992) Cyclosporin A treatment of young children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35(9):884–888
Kaizer EC, Glaser CL et al (2007) Gene expression in peripheral blood mononuclear cells from children with diabetes. J Clin Endocrinol Metab 92(9):3705–3711
Karlsen AE, Hagopian WA et al (1991) Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc Natl Acad Sci USA 88(19):8337–8341
Kaufman D, Erlander M et al (1992) Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 89(1):283–292
Kaufman DL, Clare-Salzler M et al (1993) Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 366:69–72
Kelly WD, Lillehei RC et al (1968) Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Transplantation 6(1):827–837
Kent SC, Chen Y et al (2005) Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature 435(7039):224–228
Keymeulen B, Vandemeulebroucke E et al (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352(25):2598–2608
Keymeulen B, Candon S et al (2010a) Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients. Blood 115(6):1145–1155
Keymeulen B, Walter M et al (2010b) Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia 53(4):614–623
Kroon E, Martinson LA et al (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26(4):443–452
Klinke DJ (2008) Extent of beta cell destruction is important but insufficient to predict the onset of type 1 diabetes mellitus. PLoS ONE 3(1):e1374
Kodama S, Davis M et al (2005) The therapeutic potential of tumor necrosis factor for autoimmune disease: a mechanistically based hypothesis. Cell Mol Life Sci 62(16):1850–1862
Koulmanda M, Bhasin M et al (2012) The Role of TNF-α in Mice with Type 1-and 2-Diabetes. PLoS ONE 7(5):e33254
Krishna M, Huissoon A (2011) Clinical immunology review series: an approach to desensitization. Clin Exp Immunol 163(2):131–146
Kabelitz D, Geissler EK et al (2008) Toward cell-based therapy of type I diabetes. Trends Immunol 29(2):68–74
Keselowsky BG, Xia CQ et al (2011) Multifunctional dendritic cell-targeting polymeric microparticles- Engineering new vaccines for type 1 diabetes. Hum Vaccines 7(1):37–44
Kim SJ, Nian C et al (2009) Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes 58(3):641–651
Kamal M, Al Abbasy AJ et al (2006) Effect of nicotinamide on newly diagnosed type 1 diabetic children. Acta Pharmacol Sin 27(6):724–727
Lahl K, Loddenkemper C et al (2007) Selective depletion of Foxp3 + regulatory T cells induces a scurfy-like disease. J Exp Med 204(1):57–63
Larsen CM, Faulenbach M et al (2007) Interleukin-1–receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356(15):1517–1526
Lazar L, Ofan R et al (2007) Heat-shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double-blind phase II study. Diab Metab Res Rev 23(4):286–291
Lenschow DJ, Zeng Y et al (1992) Long-term survival of xenogenic pancreatic islet grafts induced by CTLA4Ig. Science 257:789–792
Lenschow DJ, Herold KC et al (1996) CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes. Immunity 5(3):285–293
Levy LM, Dalakas MC et al (1999) The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of γ-aminobutyric acid. Ann Intern Med 131(7):522–530
Li A, Escher A (2011) Immunotherapy for type 1 diabetes-preclinical and clinical trials. In: Wagner D (ed) Type 1 diabetes—pathogenesis, genetics and immunotherapy. ISBN: 978-953-307-362-0. doi:10.5772/22049. http://www.intechopen.com/books/type-1-diabetes-pathogenesis-genetics-and-immunotherapy/immunotherapy-for-type-1-diabetes-preclinical-and-clinical-trials( InTech)
Limbert C, Päth G et al (2008) Beta-cell replacement and regeneration: strategies of cell-based therapy for type 1 diabetes mellitus. Diab Res Clin Pract 79(3):389–399
Lipsett M, Aikin R et al (2006) Islet neogenesis: a potential therapeutic tool in type 1 diabetes. Int J Biochem Cell Biol 38(5–6):715–720
Liu W, Putnam AL et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4 + T reg cells. J Exp Med 203(7):1701–1711
Lohmann T, Hawa M et al (2000) Immune reactivity to glutamic acid decarboxylase 65 in stiff-man syndrome and type 1 diabetes mellitus. Lancet 356(9223):31–35
Long SA, Rieck M et al (2012) Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments tregs yet transiently impairs β-cell function. Diabetes 61(9):2340–2348
Looney R (2005) B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. Rheumatology (Oxford) 44(Suppl 2):ii(13)–(17)
Ludvigsson J, Heding L et al (1983) Plasmapheresis in the initial treatment of insulin-dependent diabetes mellitus in children. Br Med J (Clin Res Ed) 286(6360):176–178
Ludvigsson J, Faresjö M et al (2008) GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359(18):1909–1920
Ludvigsson J (2009) The role of immunomodulation therapy in autoimmune diabetes. J Diab Sci Technol 3(2):320–330
Ludvigsson J, Hjorth M et al (2011) Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. Diabetologia 54(3):634–640
Ludvigsson J, Krisky D et al (2012) GAD65 Antigen therapy in recently diagnosed type 1 diabetes mellitus. N Engl J Med 366(5):433–442
Machen J, Harnaha J et al (2004) Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol 173(7):4331–4341
Marek-Trzonkowska N, Mysliwiec M et al (2012) Administration of CD4 + CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diab Care 35(9):1817–1820
Martin F, Chan AC (2006) B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 24:467–496
Masteller EL, Warner MR et al (2005) Expansion of functional endogenous antigen-specific CD4 + CD25 + regulatory T cells from nonobese diabetic mice. J Immunol 175(5):3053–3059
Mastrandrea L, Yu J et al (2009) Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study. Diab Care 32(7):1244–1249
Matthews J, Staeva T et al (2010) Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN–JDRF type 1 diabetes combination therapy assessment group. Clin Exp Immunol 160(2):176–184
Mercer F, Unutmaz D (2009) The biology of FoxP3: a key player in immune suppression during infections, autoimmune diseases and cancer. Adv Exp Med Biol 665:47–59
Millington OR, Mowat AMI et al (2004) Induction of bystander suppression by feeding antigen occurs despite normal clonal expansion of the bystander T cell population. J Immunol 173(10):6059–6064
Miyara M, Sakaguchi S (2007) Natural regulatory T cells: mechanisms of suppression. Trends Mol Med 13(3):108–116
Morelli AE, Thomson AW (2007) Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 7(8):610–621
Mukherjee R, Chaturvedi P et al (2003) 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 21(3):221–237
Nakayama M, Abiru N et al (2005) Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 435(7039):220–223
Nanji SA, Shapiro A (2006) Advances in pancreatic islet transplantation in humans. Diab Obes Metab 8(1):15–25
Näntö-Salonen K, Kupila A et al (2008) Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double -blind, randomised controlled trial. Lancet 372(9651):1746–1755
Narayan VKM, Zhang P et al (2006) Diabetes: the pandemic and potential solutions. In: Jamson DT, Breman JG et al (eds) Disease control priorities in development countries. Oxford University Press, World Bank, Washington, pp 591–603
Orban T, Farkas K et al (2010) Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy. J Autoimm 34(4):408–415
Orban T, Bundy B et al (2011) Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet 378(9789):412–419
Parker MJ, Xue S et al (2009) Immune depletion with cellular mobilization imparts immunoregulation and reverses autoimmune diabetes in nonobese diabetic mice. Diabetes 58(10):2277–2284
Peakman M, Von Herrath M (2010) Antigen-specific immunotherapy for type 1 diabetes: maximizing the potential. Diabetes 59(9):2087–2093
Perrin PJ, Scott D et al (1995) Role of B7: CD28/CTLA-4 in the induction of chronic relapsing experimental allergic encephalomyelitis. J Immunol 154(3):1481–1490
Pescovitz MD, Greenbaum CJ et al (2009) Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med 361(22):2143–2152
Pescovitz MD, Torgerson TR et al (2011) Effect of rituximab on human in vivo antibody immune responses. J Allergy Clin Immunol 128(6):1295–1302(e1295)
Pickup JC, Zhi ZL et al (2008) Nanomedicine and its potential in diabetes research and practice. Diab Metab Res Rev 24(8):604–610
Powers AC (2008) Insulin therapy versus cell-based therapy for type 1 diabetes mellitus: what lies ahead? Nat Clin Pract Endocrinol Metab 4(12):664–665
Pozzilli P, Pitocco D et al (2000) No effect of oral insulin on residual beta-cell function in recent-onset type I diabetes (the IMDIAB VII). IMDIAB Group. Diabetologia 43(8):1000–1004
Qin S, Cobbold SP et al (1993) “Infectious” transplantation tolerance. Science 259(5097):974–977
Quintana FJ, Carmi P et al (2003) DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. J Immunol 171(7):3533–3541
Rabinovitch A, Suarez-Pinzon WL (2007) Roles of cytokines in the pathogenesis and therapy of type 1 diabetes. Cell Biochem Biophys 48(2–3):159–163
Rabinovitch A, Suarez-Pinzon WL et al (2002) Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice. Diabetes 51(3):638–645
Ragno S, Colston MJ et al (1997) Protection of rats from adjuvant arthritis by immunization with naked DNA encoding for mycobacterial heat shock protein 65. Arthritis Rheum 40(2):277–283
Raz I, Ziegler AG et al (2014) Treatment of recent-onset type 1 diabetic patients with DiaPep277: results of a double-blind, placebo-controlled, randomized phase 3 trial. Diab Care 37(5):1392–1400
Raz I, Avron A et al (2007) Treatment of new-onset type 1 diabetes with peptide DiaPep277 is safe and associated with preserved beta-cell function: extension of a randomized, double-blind, phase II trial. Diab Metab Res Rev 23(4):292–298
Raz I, Elias D et al (2001) [beta]-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet 358(9295):1749–1753
Renard E (2002) Implantable closed-loop glucose-sensing and insulin delivery: the future for insulin-pump therapy. Curr Opin Pharmacol 2:708–716
Renard E, Schaepelynck BP (2007) Impalntable insulin pumps. A position statement about their clincal use. Diab Metab 33(2):158–166
Renard E (2015) Continous intraperitoneal insulin infusion from implantable pumps. In: Bruttomesso D, Grassi G (eds) Technological advances in the treatment of type 1 diabetes, vol 24., Front DiabetesBasel, Karger, pp 190–209
Rewers M, Gottlieb P (2009) Immunotherapy for the prevention and treatment of type 1 diabetes. Diab Care 32(10):1769–1782
Rigby MR, Trexler AM et al (2008) CD28/CD154 blockade prevents autoimmune diabetes by inducing nondeletional tolerance after effector t-cell inhibition and regulatory T-cell expansion. Diabetes 57(10):2672–2683
Roep B, Atkinson M (2004) Animal models have little to teach us about type 1 diabetes: 1. In support of this proposal. Diabetologia 47(10):1650–1656
Rosenberg L, Lipsett M et al (2004) A pentadecapeptide fragment of islet neogenesis-associated protein increases beta-cell mass and reverses diabetes in C57BL/6 J mice. Ann Surg 240(5):875–884
Rother KI, Spain LM et al (2009) Effects of exenatide alone and in combination with daclizumab on β-cell function in long-standing type 1 diabetes. Diab Care 32(12):2251–2257
Ryan EA, Lakey JRT et al (2001) Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50(4):710–719
Ryan EA, Paty BW et al (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54(7):2060–2069
Sai P, Damgé C et al (1996) Prophylactic oral administration of metabolically active insulin entrapped in isobutylcyanocrylate nanocapsules reduces the incidence of diabetes in nonobese diabetic mice. J Autoimmun 9(6):713–722
Salomon B, Lenschow DJ et al (2000) B7/CD28 costimulation is essential for the homeostasis of the CD4 + CD25 + immunoregulatory T cells that control autoimmune diabetes. Immunity 12(4):431–440
Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19(1):225–252
Sakaguchi S (2004) Naturally arising CD4 + regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562
Saudek F, Havrdova T et al (2004) Polyclonal anti-T-cell therapy for type 1 diabetes mellitus of recent onset. Rev Diab Stud 1(2):80–88
Schloot NC, Meierhoff G et al (2007) Effect of heat shock protein peptide DiaPep277 on beta-cell function in paediatric and adult patients with recent-onset diabetes mellitus type 1: two prospective, randomized, double-blind phase II trials. Diab Metab Res Rev 23(4):276–285
Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13(4):136–14
Schneider DA, Sarikonda G et al (2012) Combination therapy with InsB9-23 peptide immunization and CTLA4-IgG does not reverse diabetes in NOD mice. Clin Immunol 142(3):402–403
Selmani Z, Naji A et al (2008) Human leukocyte antigen G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4 + CD25highFOXP3 + regulatory T cells. Stem Cells 26(1):212–222
Serreze DV, Silveira PA (2003) The role of B lymphocytes as key antigen-presenting cells in the development of T cell-mediated autoimmune type 1 diabetes. Curr Dir Autoimmun 6:212–227
Sesardic D, Rijpkema S et al (2007) New adjuvants: EU regulatory developments. Expert Rev Vaccines 6(5):849–861
Sherry N, Hagopian W et al (2011) Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet 378(9790):487–497
Simon G, Parker M et al (2008) Murine antithymocyte globulin therapy alters disease progression in NOD mice by a time-dependent induction of immunoregulation. Diabetes 57(2):405–414
Shapiro AM, Ricordi C et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355(13):1318–1330
Sherry NA, Chen W et al (2007) Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells. Endocrinol 148(11): 5136–5144
Skyler J, Krischer J et al (2005) Effects of oral insulin in relatives of patients with type 1 diabetes: the diabetes prevention trial-type 1. Diab Care 28(5):1068–1076
Skyler JS (2008) Update on worldwide efforts to prevent type 1 diabetes. Ann NY Acad Sci 1150(1):190–196
Slobodan C, Christian B et al (2011) Antigen-based immune therapeutics for type 1 diabetes: magic bullets or ordinary blanks? Clin Dev Immunol 2011:286248
SoRelle JA, Naziruddin B (2011) Beta cell replacement therapy. In: Wagner D (ed) Type 1 diabetes—pathogenesis, genetics and immunotherapy. ISBN: 978-953-307-362-0. doi:10.5772/22283. http://www.intechopen.com/books/type-1-diabetes-pathogenesis-genetics-and-immunotherapy/beta-cell-replacement-therapy (InTech)
Soria B, Roche E et al (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49(2):157–162
Spoerl S, Li XC (2011) Regulatory T cells and the quest for transplant tolerance. Discov Med 11(56):25–34
Sreenan S, Pick AJ et al (1999) Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48(5):989–996
Steinman RM, Hawiger D et al (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21(1):685–711
Steinman RM (2008) Dendritic cells in vivo: a key target for a new vaccine science. Immunity 29:319–324
Stiller C, Dupre J et al (1984) Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science 223(4643):1362–1367
Suarez-Pinzon WL, Lakey JRT et al (2008) Combination therapy with glucagon-like peptide-1 and gastrin induces-cell neogenesis from pancreatic duct cells in human islets transplanted in immunodeficient diabetic mice. Cell Transplant 17(6):631–640
Sumpter KM, Adhikari S et al (2011) Preliminary studies related to anti-interleukin-1beta therapy in children with newly diagnosed type 1 diabetes. Pediatr Diab 12(7):656–667
Sun Y, Chen L et al (2007) Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J 120(9):771–776
Suntharalingam G, Perry MR et al (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 355(10):1018–1028
Sutherland DER, Gruessner A et al (2004) Beta-cell replacement therapy (pancreas and islet transplantation) for treatment of diabetes mellitus: an integrated approach. Tranplant Proc 36(6):1697–1699
Tang Q, Henriksen KJ et al (2003) Cutting edge: CD28 controls peripheral homeostasis of CD4 + CD25 + regulatory T cells. J Immunol 171(7):3348–3352
Tang Q, Henriksen KJ et al (2004) In vitro–expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199(11):1455–1465
Tarbell KV, Petit L et al (2007) Dendritic cell–expanded, islet-specific CD4 + CD25 + CD62L + regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med 204(1):191–201
Thomas D, Zaccone P et al (2005) The role of regulatory T cell defects in type 1 diabetes and the potential of these cells for therapy. Rev Diab Stud 2(1):9–18
Thomas HE, Irawaty W et al (2004) IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes 53:113–121
Thomson JA, Itskovitz-Eldor J et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147
Thornton AM, Piccirillo CA et al (2004) Activation requirements for the induction of CD4 + CD25 + T cell suppressor function. Eur J Immunol 34(2):366–376
Thrower S, James L et al (2009) Proinsulin peptide immunotherapy in type 1 diabetes: report of a first-in-man Phase I safety study. Clin Exp Immunol 155(2):156–165
Tian J, Atkinson MA et al (1996) Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J Exp Med 183(4):1561–1567
Tisch R, Wang B et al (1999) Induction of glutamic acid decarboxylase 65-specific Th2 cells and suppression of autoimmune diabetes at late stages of disease is epitope dependent. J Immunol 163(3):1178–1187
Trzonkowski P, Bieniaszewska M et al (2009) First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4 + CD25 + CD127 − T regulatory cells. Clin Immunol 133(1):22–26
Tuccinardi D, Fioriti E et al (2011) DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes. Expert Opin Biol Ther 11(9):1233–1240
Ugrasbul F, Moore WV et al (2008) Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat. Pediatr Diab 9(6):596–601
Uibo R, Lernmark A (2008) GAD65 autoimmunity-clinical studies. Adv Immunol 100:39–78
Vignali DA, Collison LW et al (2008) How regulatory T cells work. Nat Rev Immunol 8(7):523–532
Vija L, Farge D et al (2009) Mesenchymal stem cells: stem cell therapy perspectives for type 1 diabetes. Diab Metab 35(2):85–93
Voltarelli JC, Couri CE et al (2007) Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 297(14):1568–1579
Waldron-Lynch F, Herold KC (2011) Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes. Nat Rev Drug Discov 10(6):439–452
Walter M, Philotheou A et al (2009) No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes. Diab Care 32(11):2036–2040
Werdelin O, Cordes U et al (1998) Aberrant expression of tissue-specific proteins in the thymus: a hypothesis for the development of central tolerance. Scand J Immunol 47(2):95–100
Wherrett DK, Bundy B et al (2011) Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet 378(9788):319–327
Yang XD, Tisch R et al (1994) Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med 180(3):995–1004
Yi H, Zhen Y et al (2006) The phenotypic characterization of naturally occurring regulatory CD4 + CD25 + T cells. Cell Mol Immunol 3(3):189–195
Zhang ZJ, Davidson L et al (1991) Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc Natl Acad Sci USA 88(22):10252–10256
Zhao Z, Leong KW (1996) Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci 85:1261–1270
Zheng XX, Steele AW et al (1999) IL-2 receptor-targeted cytolytic IL-2/Fc fusion protein treatment blocks diabetogenic autoimmunity in nonobese diabetic mice. J Immunol 163(7):4041–4048
Zheng Y, Rudensky AY (2007) Foxp3 in control of the regulatory T cell lineage. Nat Immunol 8(5):457–462
Zimmermann H, Zimmermann D et al (2005) Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation. J Mater Sci Mater Med 16(6):491–501
Zulewski H (2006) Stem cells with potential to generate insulin-producing cells in man. Swiss Med Wkly 136(Suppl 155):60S–67S
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Singh, P. et al. (2016). Type 1 Diabetes: Past, Present, and Future Therapies. In: Therapeutic Perspectives in Type-1 Diabetes. SpringerBriefs in Applied Sciences and Technology. Springer, Singapore. https://doi.org/10.1007/978-981-10-0602-9_4
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