Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases

Frontiers in Immunology

Volumn 4, Issue AUG, 2013, Pages

  Keijzer, Chantal ^a   Van der Zee, Ruurd ^a   Van Eden, Willem ^a   Broere, Femke ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Autoimmunity; Immunologic adjuvants; Regulatory T cells; Therapeutic vaccines; Treg inducing adjuvants

Indexed keywords

ALUMINUM POTASSIUM SULFATE; CHAPERONIN 60; CHOLERA TOXIN B SUBUNIT; COLECALCIFEROL DERIVATIVE; COLLAGEN TYPE 2; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DEXAMETHASONE; DIAPEP 277; DRUG ANTIBODY; ES 62; EVEROLIMUS; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 70; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 2 ANTIBODY; LEFLUNOMIDE; LIPOSOME; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PATTERN RECOGNITION RECEPTOR; PEPTIDE; POLYGLACTIN; POLYSTYRENE; RAPAMYCIN; RETINOIC ACID; T LYMPHOCYTE RECEPTOR; TACROLIMUS; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADJUVANT THERAPY; ALLERGIC ENCEPHALOMYELITIS; ARTHRITIS; AUTOIMMUNE DISEASE; COLLAGEN-INDUCED ARTHRITIS; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOREGULATION; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INSULIN DEPENDENT DIABETES MELLITUS; JUVENILE DERMATOMYOSITIS; JUVENILE RHEUMATOID ARTHRITIS; MUCOSAL VACCINATION; MULTIPLE SCLEROSIS; NONHUMAN; PHASE 3 CLINICAL TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; SINGLE DRUG DOSE; VACCINATION;

EID: 84883733883     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00245     Document Type: Review

References (88)

1. Chen Y, Kuchroo V, Inobe J, Hafler D, Weiner H. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science (1994) 265(5176):1237-40. doi:10.1126/science.7520605
2. Sakaguchi S, Wing K, Miyara M. Regulatory T cells? A brief history and perspective. Eur J Immunol (2007) 37(S1):S116-23. doi:10.1002/eji.200737593
3. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol (2008) 8(7):523-32. doi:10.1038/nri2343
4. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity (2009) 30(5):636-45. doi:10.1016/j.immuni.2009.04.010
5. Thornton A, Shevach E. Suppressor effector function of CD4(+)CD25(+) immunoregulatory T cells is antigen nonspecific. J Immunol (2000) 164(1):183-90.
6. Strachan DP. Hay fever, hygiene, and household size. BMJ (1989) 299(6710):1259-60. doi:10.1136/bmj.299.6710.1259
7. Rook GA. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Darwinian medicine and the 'hygiene' or 'old friends' hypothesis. Clin Exp Immunol (2010) 160(1):70-9. doi:10.1111/j.1365-2249
8. van Eden W, van der Zee R, Prakken B. Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol (2005) 5(4):318-30. doi:10.1038/nri1593
9. Van Puijvelde GHM, Van Es T, Van Wanrooij EJA, Habets KLL, De Vos P, Van Der Zee R, et al. Induction of oral tolerance to HSP60 or an HSP60-peptide activates t cell regulation and reduces atherosclerosis. Arterioscler Thromb Vasc Biol (2007) 27(12):2677-83. doi:10.1161/ATVBAHA.107.151274
10. Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J, et al. Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci U S A (2004) 101(12):4228-33. doi:10.1073/pnas.0400061101
11. Koffeman EC, Genovese M, Amox D, Keogh E, Santana E, Matteson EL, et al. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum (2009) 60(11):3207-16. doi:10.1002/art.24916
12. Borges TJ, Porto BN, Teixeira CA, Rodrigues M, Machado FD, Ornaghi AP, et al. Prolonged survival of allografts induced by mycobacterial Hsp70 is dependent on CD4+CD25+ regulatory T cells. PLoS ONE (2010) 5(12):e14264. doi:10.1371/journal.pone.0014264
13. Raz I, Elias D, Avron A, Tamir M, Metzger M, Cohen IR. 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 (2001) 358(9295):1749-53. doi:10.1016/S0140-6736(01)06801-5
14. Raz I, Avron A, Tamir M, Metzger M, Symer L, Eldor R, et al. 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. Diabetes Metab Res (2007) 23(4):292-8. doi:10.1002/dmrr.712
15. Tuccinardi D, Fioriti E, Manfrini S, D'Amico E, Pozzilli P. DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes. Expert Opin Biol Ther (2011) 11(9):1233-40. doi:10.1517/14712598.2011.599319
16. Petrarca C, Lazzarin F, Pannellini T, Iezzi M, Braga M, Mistrello G, et al. Monomeric allergoid intragastric administration induces local and systemic tolerogenic response involving IL-10-producing CD4(+)CD25(+) T regulatory cells in mice. Int J Immunopathol Pharmacol (2010) 23(4):1021-31.
17. Wu HY, Nguyen HH, Russell MW. Nasal lymphoid tissue (NALT) as a mucosal immune inductive site. Scand J Immunol (1997) 46(5):506-13. doi:10.1046/j.1365-3083.1997.d01-159.x
18. Davis SS. Nasal vaccines. Adv Drug Deliv Rev (2001) 51(1-3):21-42. doi:10.1016/S0169-409X(01)00162-4
19. Unger WWJ, Hauet-Broere F, Jansen W, van Berkel LA, Kraal G, Samsom JN. Early events in peripheral regulatory T cell induction via the nasal mucosa. J Immunol (2003) 171(9):4592-603.
20. Horwitz DA, Zheng SG, Gray JD. Natural and TGF-ß-induced Foxp3+CD4+ CD25+ regulatory T cells are not mirror images of each other. Trends Immunol (2008) 29(9):429-35. doi:10.1016/j.it.2008.06.005
21. Couch RB. Nasal vaccination, Escherichia coli enterotoxin, and Bell's palsy. N Engl J Med (2004) 350(9):860-1. doi:10.1056/NEJMp048006
22. Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N Engl J Med (2004) 350(9):896-903. doi:10.1056/NEJMoa030595
23. Prabakaran M, Velumani S, He F, Karuppannan AK, Geng GY, Yin LK, et al. Protective immunity against influenza H5N1 virus challenge in mice by intranasal co-administration of baculovirus surface-displayed HA and recombinant CTB as an adjuvant. Virology (2008) 380(2):412-20. doi:10.1016/j.virol.2008.08.002
24. Isaka M, Zhao Y, Nobusawa E, Nakajima S, Nakajima K, Yasuda Y, et al. Protective effect of nasal immunization of influenza virus hemagglutinin with recombinant cholera toxin B subunit as a mucosal adjuvant in mice. Microbiol Immunol (2008) 52(2):55-63. doi:10.1111/j.1348-0421.2008.00010.x
25. Sun J, Flach C, Czerkinsky C, Holmgren J. B lymphocytes promote expansion of regulatory T cells in oral tolerance: powerful induction by antigen coupled to cholera toxin B subunit. J Immunol (2008) 181(12):8278-87.
26. Ploix C, Bergerot I, Durand A, Czerkinsky C, Holmgren J, Thivolet C. Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4 regulatory T-cells. Diabetes (1999) 48(11):2150-6. doi:10.2337/diabetes.48.11.2150
27. Klingenberg R, Lebens M, Hermansson A, Fredrikson GN, Strodthoff D, Rudling M, et al. Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis. Arterioscler Thromb Vasc Biol (2010) 30(5):946-52. doi:10.1161/ATVBAHA.109.202671
28. Agren LC, Ekman L, Löwenadler B, Lycke NY. Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. J Immunol (1997) 158(8):3936-46.
29. Hasselberg A, Ekman L, Yrlid LF, Schön K, Lycke NYADP-. ribosylation controls the outcome of tolerance or enhanced priming following mucosal immunization. J Immunol (2010) 184(6):2776-84. doi:10.4049/jimmunol.0901445
30. Patel M, Xu D, Kewin P, Choo-Kang B, McSharry C, Thomson NC, et al. TLR2 agonist ameliorates established allergic airway inflammation by promoting Th1 response and not via regulatory T cells. J Immunol (2005) 174(12):7558-63.
31. Kiura K, Kataoka H, Yasuda M, Inoue N, Shibata K. The diacylated lipopeptide FSL-1 induces TLR2-mediated Th2 responses. FEMS Immunol Med Microbiol (2006) 48(1):44-55. doi:10.1111/j.1574-695X.2006.00119.x
32. Sutmuller RP, den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg B, et al. Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest (2006) 116(2):485-94. doi:10.1172/JCI25439
33. DePaolo RW, Kamdar K, Khakpour S, Sugiura Y, Wang W, Jabri B. A specific role for TLR1 in protective TH17 immunity during mucosal infection. J Exp Med (2012) 209(8):1437-44. doi:10.1084/jem.20112339
34. Nawijn MC, Motta AC, Gras R, Shirinbak S, Maazi H, van Oosterhout AJ. TLR-2 activation induces regulatory T cells and long-term suppression of asthma manifestations in mice. PLoS ONE (2013) 8(2):e55307. doi:10.1371/journal.pone.0055307
35. Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest (2006) 116(4):916-28. doi:10.1172/JCI27203
36. DePaolo RW, Tang F, Kim I, Han M, Levin N, Ciletti N, et al. Toll-like receptor 6 drives differentiation of tolerogenic dendritic cells and contributes to LcrV-mediated plague pathogenesis. Cell Host Microbe (2008) 4(4):350-61. doi:10.1016/j.chom.2008.09.004
37. Aldridge S. Toll-like receptor blocker slows beta cell death in type 1 diabetes. Nat Biotechnol (2012) 30(2):124-124c. doi:10.1038/nbt0212-124c
38. Nyirenda MH, Sanvito L, Darlington PJ, O'Brien K, Zhang G, Constantinescu CS, et al. TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function. J Immunol (2011) 187(5):2278-90. doi:10.4049/jimmunol.1003715
39. Zaccone P, Fehervari Z, Phillips J, Dunne D, Cooke A. Parasitic worms and inflammatory diseases. Parasite Immunol (2006) 28(10):515-23. doi:10.1111/j.1365-3024.2006.00879.x
40. Song X, Shen J, Wen H, Zhong Z, Luo Q, Chu D, et al. Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1 mice: a murine model of human rheumatoid arthritis. PLoS ONE (2011) 6(8):e23453. doi:10.1371/journal.pone.0023453
41. Blum AM, Hang L, Setiawan T, Urban JP, Stoyanoff KM, Leung J, et al. Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses. J Immunol (2012) 189(5):2512-20. doi:10.4049/jimmunol.1102892
42. Wilson MS, Taylor MD, O'Gorman MT, Balic A, Barr TA, Filbey K, et al. Helminth-induced CD19 CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol (2010) 40(6):1682-96. doi:10.1002/eji.200939721
43. Langelaar M, Aranzamendi C, Franssen F, Van der Giessen J, Rutten V, Van der Ley P, et al. Suppression of dendritic cell maturation by Trichinella spiralis excretory/secretory products. Parasite Immunol (2009) 31(10):641-5. doi:10.1111/j.1365-3024.2009.01136.x
44. Kuijk LM, Klaver EJ, Kooij G, van der Pol S, Heijnen P, Bruijns S, et al. Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation. Mol Immunol (2012) 51(2):210-8. doi:10.1016/j.molimm.2012.03.020
45. Aranzamendi C, Fransen F, Langelaar M, Franssen F, Van Der LEYP, Van PUTTEN J, et al. Trichinella spiralis secreted products modulate DC functionality and expand regulatory T cells in vitro. Parasite Immunol (2012) 34(4):210-23. doi:10.1111/j.1365-3024.2012.01353.x
46. Gruden-Movsesijan A, Ilic N, Colic M, Majstorovic I, Vasilev S, Radovic I, et al. The impact of Trichinella spiralis excretory-secretory products on dendritic cells. Comp Immunol Microbiol Infect Dis (2011) 34(5):429-39. doi:10.1016/j.cimid.2011.08.004
47. van der Kleij D, Latz E, Brouwers JF, Kruize Y, Schmitz M, Kurt-Jones EA, et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. Sci Signal (2002) 277(50):48122.
48. Pineda MA, McGrath MA, Smith PC, Al-Riyami L, Rzepecka J, Gracie JA, et al. The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17-producing cellular network at multiple sites. Arthritis Rheum (2012) 64(10):3168-78. doi:10.1002/art.34581
49. Keijzer C, Spiering R, Silva AL, van Eden W, Jiskoot W, Vervelde L, et al. PLGA nanoparticles enhance the expression of retinaldehyde dehydrogenase enzymes in dendritic cells and induce FoxP3(+) T-cells in vitro. J Controlled Release (2013) 168(1):35-40. doi:10.1016/j.jconrel.2013.02.027
50. Waeckerle-Men Y, Allmen EU, Gander B, Scandella E, Schlosser E, Schmidtke G, et al. Encapsulation of proteins and peptides into biodegradable poly (D, L-lactide-co-glycolide) microspheres prolongs and enhances antigen presentation by human dendritic cells. Vaccine (2006) 24(11):1847-57. doi:10.1016/j.vaccine.2005.10.032
51. Kim WU, Lee WK, Ryoo JW, Kim SH, Kim J, Youn J, et al. Suppression of collagen-induced arthritis by single administration of poly(lactic-co-glycolic acid) nanoparticles entrapping type II collagen: a novel treatment strategy for induction of oral tolerance. Arthritis Rheum (2002) 46(4):1109-20. doi:10.1002/art.10198
52. Keijzer C, Slutter B, van der Zee R, Jiskoot W, van Eden W, Broere FPLGA. PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity. PLoS ONE (2011) 6(11):e26684. doi:10.1371/journal.pone.0026684
53. Getts DR, Martin AJ, McCarthy DP, Terry RL, Hunter ZN, Yap WT, et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol (2012) 30(12):1217-24. doi:10.1038/nbt.2434
54. Bangham A, Standish M, Watkins J. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol (1965) 13(1): 238-IN27. doi:10.1016/S0022-2836(65)80093-6
55. Capini C, Jaturanpinyo M, Chang H, Mutalik S, McNally A, Street S, et al. Antigen-specific suppression of inflammatory arthritis using liposomes. J Immunol (2009) 182(6):3556-65. doi:10.4049/jimmunol.0802972
56. Kretschmer K, Heng TS, von Boehmer H. De novo production of antigen-specific suppressor cells in vivo. Nat Protoc (2006) 1(2):653-61. doi:10.1038/nprot.2006.105
57. Hackstein H, Thomson AW. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat Rev Immunol (2004) 4(1):24-35. doi:10.1038/nri1256
58. Laplante M, Sabatini DM. Regulation of mTORC1 and its impact on gene expression at a glance. J Cell Sci (2013) 126(Pt 8):1713-9. doi:10.1242/jcs.125773
59. Wang C, Yi T, Qin L, Maldonado RA, von Andrian UH, Kulkarni S, et al. Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells. J Clin Invest (2013) 123(4):1677-93. doi:10.1172/JCI66204
60. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood (2005) 105(12):4743-8. doi:10.1182/blood-2004-10-3932
61. Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo M. Rapamycin promotes expansion of functional CD4 CD25 FOXP3 regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol (2006) 177(12):8338-47.
62. Monti P, Scirpoli M, Maffi P, Piemonti L, Secchi A, Bonifacio E, et al. Rapamycin monotherapy in patients with type 1 diabetes modifies CD4 CD25 FOXP3 regulatory T-cells. Diabetes (2008) 57(9):2341-7. doi:10.2337/db08-0138
63. Ogino H, Nakamura K, Iwasa T, Ihara E, Akiho H, Motomura Y, et al. Regulatory T cells expanded by rapamycin in vitro suppress colitis in an experimental mouse model. J Gastroenterol (2012) 47(4):366-76. doi:10.1007/s00535-011-0502-y
64. Esposito M, Ruffini F, Bellone M, Gagliani N, Battaglia M, Martino G, et al. Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation. J Neuroimmunol (2010) 220(1):52-63. doi:10.1016/j.jneuroim.2010.01.001
65. Donia M, Mangano K, Amoroso A, Mazzarino MC, Imbesi R, astrogiovanni P, et al. Treatment with rapamycin ameliorates clinical and histological signs of protracted relapsing experimental allergic encephalomyelitis in Dark Agouti rats and induces expansion of peripheral CD4 CD25 Foxp3 regulatory T cells. J Autoimmun (2009) 33(2):135-40. doi:10.1016/j.jaut.2009.06.003
66. Wu T, Zhang L, Xu K, Sun C, Lei T, Peng J, et al. Immunosuppressive drugs on inducing Ag-specific CD4 CD25 Foxp3 Treg cells during immune response in vivo. Transpl Immunol (2012) 27(1):30-8. doi:10.1016/j.trim.2012.05.001
67. Daniel C, Wennhold K, Kim H, von Boehmer H. Enhancement of antigen-specific Treg vaccination in vivo. Proc Natl Acad Sci U S A (2010) 107(37):16246-51. doi:10.1073/pnas.1007422107
68. Kang Y, Zhao J, Liu Y, Chen A, Zheng G, Yu Y, et al. FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitis. J Gene Med (2009) 11(11):1064-70. doi:10.1002/jgm.1387
69. Taher YA, van Esch BC, Hofman GA, Henricks PA, van Oosterhout AJ. 1a, 25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-ß. J Immunol (2008) 180(8):5211-21.
70. Ghoreishi M, Bach P, Obst J, Komba M, Fleet JC, Dutz JP. Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol. J Immunol (2009) 182(10):6071-8. doi:10.4049/jimmunol.0804064
71. Manicassamy S, Pulendran B. Retinoic acid-dependent regulation of immune responses by dendritic cells and macrophages. Semin Immunol (2009) 21(1):22-7. doi:10.1016/j.smim.2008.07.007
72. Hall JA, Grainger JR, Spencer SP, Belkaid Y. The role of retinoic acid in tolerance and immunity. Immunity (2011) 35(1):13-22. doi:10.1016/j.immuni.2011.07.002
73. Kwok S, Park M, Cho M, Oh H, Park E, Lee D, et al. Retinoic acid attenuates rheumatoid inflammation in mice. J Immunol (2012) 189(2):1062-71. doi:10.4049/jimmunol.1102706
74. Van Y, Lee W, Ortiz S, Lee M, Qin H, Liu C. All-trans retinoic acid inhibits type 1 diabetes by T regulatory (Treg)-dependent suppression of interferon-?-producing T-cells without affecting Th17 cells. Diabetes (2009) 58(1):146-55. doi:10.2337/db08-1154
75. Kishi M, Yasuda H, Abe Y, Sasaki H, Shimizu M, Arai T, et al. Regulatory CD8+ T cells induced by exposure to all-trans retinoic acid and TGF-ß suppress autoimmune diabetes. Biochem Biophys Res Commun (2010) 394(1):228-32. doi:10.1016/j.bbrc.2010.02.176
76. Stephenson I, Nicholson KG, Colegate A, Podda A, Wood J, Ypma E, et al. Boosting immunity to influenza H5N1 with MF59-adjuvanted H5N3 A/Duck/Singapore/97 vaccine in a primed human population. Vaccine (2003) 21(15):1687-93. doi:10.1016/S0264-410X(02)00632-1
77. Szarewski A, Poppe W, Skinner S, Wheeler C, Paavonen J, Naud P, et al. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18. Int J Cancer (2012) 131(1):106-16. doi:10.1002/ijc.26362
78. Hjorth M, Axelsson S, Rydén A, Faresjö M, Ludvigsson J, Casas R. GAD-alum treatment induces GAD65-specific CD4 CD25highFOXP3 cells in type 1 diabetic patients. Clin Immunol (2011) 138(1):117. doi:10.1016/j.clim.2010.10.004
79. Wigren M, Bengtsson D, Dunér P, Olofsson K, Björkbacka H, Bengtsson E, et al. Atheroprotective effects of Alum are associated with capture of oxidized LDL antigens and activation of regulatory T cells. Circ Res (2009) 104(12):e62-70. doi:10.1161/CIRCRESAHA.109.196667
80. Fousteri G, Dave A, Bot A, Juntti T, Omid S, von Herrath M. Subcutaneous insulin B: 9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFN?. Diabetologia (2010) 53(9):1958-70. doi:10.1007/s00125-010-1777-x
81. Chatenoud L. Anti-CD3 antibodies: towards clinical antigen-specific immunomodulation. Curr Opin Pharmacol (2004) 4(4):403-7. doi:10.1016/j.coph.2004.03.012
82. Belghith M, Bluestone JA, Barriot S, Mégret J, Bach J, Chatenoud L. TGF-ß-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat Med (2003) 9(9):1202-8. doi:10.1038/nm924
83. Bresson D, Togher L, Rodrigo E, Chen Y, Bluestone JA, Herold KC, et al. Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. J Clin Invest (2006) 116(5):1371-81. doi:10.1172/JCI27191
84. Steffens S, Burger F, Pelli G, Dean Y, Elson G, Kosco-Vilbois M, et al. Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice. Circulation (2006) 114(18):1977-84. doi:10.1161/CIRCULATIONAHA.106.627430
85. Razmara M, Hilliard B, Ziarani AK, Chen YH, Tykocinski ML. CTLA-4 Ig converts naive CD4 CD25- T cells into CD4 CD25 regulatory T cells. Int Immunol (2008) 20(4):471-83. doi:10.1093/intimm/dxn007
86. Ko H, Cho M, Lee S, Oh H, Heo Y, Moon Y, et al. CTLA4-Ig modifies dendritic cells from mice with collagen-induced arthritis to increase the CD4 CD25 Foxp3 regulatory T cell population. J Autoimmun (2010) 34(2):111-20. doi:10.1016/j.jaut.2009.07.006
87. Coquerelle C, Oldenhove G, Acolty V, Denoeud J, Vansanten G, Verdebout J, et al. Anti-CTLA-4 treatment induces IL-10-producing ICOS regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis. Gut (2009) 58(10):1363-73. doi:10.1136/gut.2008.162842
88. Roord ST, Zonneveld-Huijssoon E, Le T, Yung GP, Koffeman E, Ronaghy A, et al. Modulation of T cell function by combination of epitope specific and low dose anticytokine therapy controls autoimmune arthritis. PLoS ONE (2006) 1:e87. doi:10.1371/journal.pone.0000087