Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens

World Allergy Organization Journal

Volumn 8, Issue 1, 2015, Pages

  Akdis, Cezmi A ^a   Akdis, Mübeccel ^a  

^a SWISS INSTITUTE OF ALLERGY AND ASTHMA RESEARCH SIAF   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALLERGEN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G4; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 10; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA;

ALLERGEN SPECIFIC IMMUNOTHERAPY; ANTIGEN PRESENTING CELL; ARTICLE; BASOPHIL; CD4+ CD25+ T LYMPHOCYTE; CELL MIGRATION; CELLULAR IMMUNITY; DESENSITIZATION; EFFECTOR CELL; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOTHERAPY; MAST CELL; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; TH1 CELL; TH17 CELL; TH2 CELL;

EID: 84938991407     PISSN: None     EISSN: 19394551     Source Type: Journal    
DOI: 10.1186/s40413-015-0063-2     Document Type: Article

References (182)

1. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133:621-31.
2. Akdis CA. Therapies for allergic inflammation: refining strategies to induce tolerance. Nat Med. 2012;18:736-49.
3. Akdis M, Akdis AC. Immune Tolerance. In: Franklin Adkinson Jr BSB N, Wesley B, Busse WW, Holgate ST, Lemanske Jr RF, O'Hehir RE, editors. Middleton's Allergy. 8th ed. 2013.
4. Akdis M, Akdis CA. Therapeutic manipulation of immune tolerance in allergic disease. Nat Rev Drug Discov. 2009;8:645-60.
5. Akdis CA. Allergy and hypersensitivity: mechanisms of allergic disease. Curr Opin Immunol. 2006;18:718-26.
6. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2011;127:18-27. quiz 8-9.
7. Akdis C, Papadopoulos N, Cardona V. Fighting allergies beyond symptoms: the European declaration on immunotherapy. Eur J Immunol. 2011;41:2802-4.
8. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2011;127:18-27. quiz 8-9.
9. Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, et al. Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2011;127:701-21. e1-70.
10. Akkoc T, Akdis M, Akdis CA. Update in the mechanisms of allergen-specific immunotheraphy. Allergy Asthma Immunol Res. 2011;3:11-20.
11. Bousquet J, Anto J, Auffray C, Akdis M, Cambon-Thomsen A, Keil T, et al. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy. 2011;66:596-604.
12. Deniz G, Akdis M. NK cell subsets and their role in allergy. Expert Opin Biol Ther. 2011;11:833-41.
13. Direskeneli H, Fujita H, Akdis CA. Regulation of TH17 and regulatory T cells in patients with Behcet disease. J Allergy Clin Immunol. 2011;128:665-6.
14. Eiwegger T, Akdis CA. IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. Eur J Immunol. 2011;41:1535-8.
15. Eiwegger T, Gruber S, Geiger C, Meyer E, Dehlink E, Bannert C, et al. Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses. Allergy. 2011;66:271-8.
16. Fujita H, Chalubinski M, Rhyner C, Indermitte P, Meyer N, Ferstl R, et al. Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects. J Allergy Clin Immunol. 2011;127:1612-21.
17. Jutel M, Akdis CA. Immunological mechanisms of allergen-specific immunotherapy. Allergy. 2011;66:725-32.
18. Jutel M, Akdis CA. T-cell subset regulation in atopy. Curr Allergy Asthma Rep. 2011;11:139-45.
19. Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127:355-60.
20. O'Mahony L, Akdis M, Akdis CA. Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol. 2011;128:1153-62.
21. Ozdemir C, Kucuksezer UC, Akdis M, Akdis CA. Specific immunotherapy and turning off the T cell: how does it work? Ann Allergy Asthma Immunol. 2011;107:381-92.
22. Ozdemir C, Kucuksezer UC, Akdis M, Akdis CA. Mechanisms of immunotherapy to wasp and bee venom. Clin Exp Allergy. 2011;41:1226-34.
23. Palomares O, O'Mahony L, Akdis CA. The many routes of dendritic cells to ensure immune regulation. J Allergy Clin Immunol. 2011;127:1541-2.
24. Sackesen C, Birben E, Soyer OU, Sahiner UM, Yavuz TS, Civelek E, et al. The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma. Allergy. 2011;66:48-57.
25. Sin BA, Akdis M, Zumkehr J, Bezzine S, Bekpen C, Lambeau G, et al. T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns. Allergy. 2011;66:1513-21.
26. Soyer OU, Akdis M, Akdis CA. Mechanisms of subcutaneous allergen immunotherapy. Immunol Allergy Clin North Am. 2011;31:175-90.
27. Vale-Pereira S, Todo-Bom A, Geraldes L, Schmidt-Weber C, Akdis CA, Mota-Pinto A. FoxP3, GATA-3 and T-bet expression in elderly asthma. Clin Exp Allergy. 2011;41:490-6.
28. Vanbervliet B, Akdis M, Vocanson M, Rozières A, Benetière J, Rouzaire P, et al. Histamine receptor H1 signaling on dendritic cells plays a key role in the IFN-gamma/IL-17 balance in T cell-mediated skin inflammation. J Allergy Clin Immunol. 2011;127:943-53. e1-10.
29. Zimmermann M, Koreck A, Meyer N, Basinski T, Meiler F, Simone B, et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-alpha cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol. 2011;127:200-7. 7 e1-10.
30. Smits HH, Akdis CA. In utero priming by worms protects against respiratory allergies. J Allergy Clin Immunol. 2014;134:1280-1.
31. Casale TB, Stokes JR. Immunotherapy: what lies beyond. J Allergy Clin Immunol. 2014;133:612-9. quiz 20.
32. Soyka MB, van de Veen W, Holzmann D, Akdis M, Akdis CA. Scientific foundations of allergen-specific immunotherapy for allergic disease. Chest. 2014;146:1347-57.
33. Jutel M, Akdis CA. Novel immunotherapy vaccine development. Curr Opin Allergy Clin Immunol. 2014;14:557-63.
34. Cavkaytar O, Akdis CA, Akdis M. Modulation of immune responses by immunotherapy in allergic diseases. Curr Opin Pharmacol. 2014;17:30-7.
35. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2007;119:780-91.
36. Akdis M. Healthy immune response to allergens: T regulatory cells and more. Curr Opin Immunol. 2006;18:738-44.
37. Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6:761-71.
38. Durham SR, Walker SM, Varga E-V, Jacobson MR, O'Brien F, Noble W, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468-75.
39. Vickery BP, Scurlock AM, Kulis M, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133:468-75.
40. Pajno GB, Barberio G, De Luca F, Morabito L, Parmiani S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy. 2001;31:1392-7.
41. Moller C, Dreborg S, Ferdousi HA, Halken S, Høst A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002;109:251-6.
42. Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131:1288-96.
43. Creticos PS, Esch RE, Couroux P, Gentile D, D'Angelo P, Whitlow B, et al. Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2014;133:751-8.
44. Wood RA, Togias A, Wildfire J, Visness CM, Matsui EC, Gruchalla R, et al. Development of cockroach immunotherapy by the Inner-City Asthma Consortium. J Allergy Clin Immunol. 2014;133:846-52.
45. Ramirez RM, Jacobs RL. Eosinophilic esophagitis treated with immunotherapy to dust mites. J Allergy Clin Immunol. 2013;132:503-4.
46. Creticos PS, Maloney J, Bernstein DI, Casale T, Kaur A, Fisher R, et al. Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults. J Allergy Clin Immunol. 2013;131:1342-9.
47. Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013;132:1248-52.
48. Tam H, Calderon MA, Boyle RJ. Efficacy of allergen-specific immunotherapy for patients with atopic dermatitis. J Allergy Clin Immunol. 2013;132:1012-3.
49. Patel P, Holdich T, von Weikersthal-Drachenberg KJ F, Huber B. Efficacy of a short course of specific immunotherapy in patients with allergic rhinoconjunctivitis to ragweed pollen. J Allergy Clin Immunol. 2014;133:121-9. e1-2.
50. Swoboda I, Balic N, Klug C, Focke M, Weber M, Spitzauer S, et al. A general strategy for the generation of hypoallergenic molecules for the immunotherapy of fish allergy. J Allergy Clin Immunol. 2013;132:979-81.
51. Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WC, Rutten-van Molken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132:353-60. e2.
52. Focke-Tejkl M, Weber M, Niespodziana K, Neubauer A, Huber H, Henning R et al. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy. J Allergy Clin Immunol 2014; article in press, published online ahead of print. (doi:10.1016/j.jaci.2014.09.012)
53. von Moos S, Johansen P, Tay F, Graf N, Kundig TM, Senti G. Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy. J Allergy Clin Immunol. 2014;134:965-7.
54. Spertini F, Perrin Y, Audran R, Pellaton C, Boudousquié C, Barbier N, et al. Safety and immunogenicity of immunotherapy with Bet v 1-derived contiguous overlapping peptides. J Allergy Clin Immunol. 2014;134:239-40.
55. Kundig TM, Johansen P, Bachmann MF, Cardell LO, Senti G. Intralymphatic immunotherapy: time interval between injections is essential. J Allergy Clin Immunol. 2014;133:930-1.
56. Holt PG, Sly PD, Sampson HA, Robinson P, Loh R, Lowenstein H, et al. Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. J Allergy Clin Immunol. 2013;132:991-3.
57. Stringari G, Tripodi S, Caffarelli C, Dondi A, Asero R, Di Rienzo Businco A, et al. The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever. J Allergy Clin Immunol. 2014;134:75-81.
58. Allam JP, Wuestenberg E, Wolf H, Klimek L, Decot E, Horn A, et al. Immunologic response and safety in birch pollen sublingual versus oral vestibule immunotherapy: a pilot study. J Allergy Clin Immunol. 2014;133:1757-9.
59. Passalacqua G, Baena-Cagnani CE, Bousquet J, Canonica GW, Casale TB, Cox L, et al. Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language. J Allergy Clin Immunol. 2013;132:93-8.
60. Jones SM, Burks AW, Dupont C. State of the art on food allergen immunotherapy: oral, sublingual, and epicutaneous. J Allergy Clin Immunol. 2014;133:318-23.
61. Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, et al. Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J. 2014;7:6.
62. Larenas-Linnemann D, Wahn U, Kopp M. Use of omalizumab to improve desensitization safety in allergen immunotherapy. J Allergy Clin Immunol. 2014;133:937. e2.
63. Kohler J, Blank S, Muller S, Bantleon F, Frick M, Huss-Marp J, et al. Component resolution reveals additional major allergens in patients with honeybee venom allergy. J Allergy Clin Immunol. 2014;133:1383-9. 9 e1-6.
64. Wang M, Takeda K, Shiraishi Y, Okamoto M, Dakhama A, Joetham A, et al. Peanut-induced intestinal allergy is mediated through a mast cell-IgE-FcepsilonRI-IL-13 pathway. J Allergy Clin Immunol. 2010;126:306-16. 16 e1-12.
65. Berin MC, Shreffler WG. T(H)2 adjuvants: implications for food allergy. J Allergy Clin Immunol. 2008;121:1311-20. quiz 21-2.
66. Chatila TA, Li N, Garcia-Lloret M, Kim HJ, Nel AE. T-cell effector pathways in allergic diseases: transcriptional mechanisms and therapeutic targets. J Allergy Clin Immunol. 2008;121:812-23. quiz 24-5.
67. Kang CM, Jang AS, Ahn MH, Shin JA, Kim JH, Choi YS, et al. Interleukin-25 and interleukin-13 production by alveolar macrophages in response to particles. Am J Respir Cell Mol Biol. 2005;33:290-6.
68. Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007;204:1837-47.
69. Dillon SR, Sprecher C, Hammond A, Bilsborough J, Rosenfeld-Franklin M, Presnell SR, et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol. 2004;5:752-60.
70. Bilsborough J, Leung DY, Maurer M, Howell M, Boguniewicz M, Yao L, et al. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2006;117:418-25.
71. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7:827-40.
72. Prefontaine D, Nadigel J, Chouiali F, Audusseau S, Semlali A, Chakir J, et al. Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol. 2010;125:752-4.
73. Rank MA, Kobayashi T, Kozaki H, Bartemes KR, Squillace DL, Kita H. IL-33-activated dendritic cells induce an atypical TH2-type response. J Allergy Clin Immunol. 2009;123:1047-54.
74. Romagnani S. Immunologic influences on allergy and the TH1/TH2 balance. J Allergy Clin Immunol. 2004;113:395-400.
75. Finotto S, Neurath MF, Glickman JN, Qin S, Lehr HA, Green FH, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science. 2002;295:336-8.
76. Akkoc T, de Koning PJ, Ruckert B, Barlan I, Akdis M, Akdis CA. Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells as a mechanism of T(H)2 predominance in atopic diseases. J Allergy Clin Immunol. 2008;121:652-8.
77. Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J Clin Invest. 2000;106:25-35.
78. Trautmann A, Schmid-Grendelmeier P, Krüger K, Crameri R, Akdis M, Akkaya A, et al. T cells and eosinophils cooperate in the induction of bronchial epithelial apoptosis in asthma. J Allergy Clin Immunol. 2002;109:329-37.
79. Meyer N, Zimmermann M, Bürgler S, Bassin C, Woehrl S, Moritz K, et al. IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis. J Allergy Clin Immunol. 2010;125:858-65.
80. Solarewicz-Madejek K, Basinski TM, Crameri R, Akdis M, Akkaya A, Blaser K, et al. T cells and eosinophils in bronchial smooth muscle cell death in asthma. Clin Exp Allergy. 2009;39:845-55.
81. Burgler S, Ouaked N, Bassin C, Basinski TM, Mantel PY, Siegmund K, et al. Differentiation and functional analysis of human T(H)17 cells. J Allergy Clin Immunol. 2009;123(3):588-95. 595.e1-7.
82. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648-51.
83. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133-41.
84. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature. 2006;441:231-4.
85. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123-32.
86. Makihara S, Okano M, Fujiwara T, Kariya S, Noda Y, Higaki T, et al. Regulation and characterization of IL-17A expression in patients with chronic rhinosinusitis and its relationship with eosinophilic inflammation. J Allergy Clin Immunol. 2010;126:397-400.
87. Martin P, Gomez M, Lamana A, Matesanz Marín A, Cortés JR, Ramírez-Huesca M, et al. The leukocyte activation antigen CD69 limits allergic asthma and skin contact hypersensitivity. J Allergy Clin Immunol. 2010;126:355-65. 65 e1-3.
88. Sergejeva S, Ivanov S, Lotvall J, Linden A. Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. Am J Respir Cell Mol Biol. 2005;33:248-53.
89. Hellings PW, Kasran A, Liu Z, Vandekerckhove P, Wuyts A, Overbergh L, et al. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol. 2003;28:42-50.
90. Bush KA, Farmer KM, Walker JS, Kirkham BW. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002;46:802-5.
91. Rangachari M, Mauermann N, Marty RR, Dirnhofer S, Kurrer MO, Komnenovic V, et al. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med. 2006;203:2009-19.
92. Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol. 2008;9:1347-55.
93. Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, et al. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008;9:1341-6.
94. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123:1244-52.
95. Akdis CA, Akdis M. Mechanisms and treatment of allergic disease in the big picture of regulatory T cells. J Allergy Clin Immunol. 2009;123:735-46. quiz 47-8.
96. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131:1479-90.
97. Rebane A, Akdis CA. MicroRNAs: essential players in the regulation of inflammation. J Allergy Clin Immunol. 2013;132:15-26.
98. Nicodemus-Johnson J, Laxman B, Stern RK, Sudi J, Tierney CN, Norwick L, et al. Maternal asthma and microRNA regulation of soluble HLA-G in the airway. J Allergy Clin Immunol. 2013;131:1496-503.
99. Lu TX, Rothenberg ME. Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases. J Allergy Clin Immunol. 2013;132:3-13. quiz 4.
100. Rebane A, Runnel T, Aab A, Maslovskaja J, Rückert B, Zimmermann M, et al. MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes. J Allergy Clin Immunol. 2014;134:836-47.
101. Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, et al. Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy. 2006;36:465-74.
102. Alexander C, Ying S, B Kay A, Larche M. Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-gamma + T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin Exp Allergy. 2005;35:52-8.
103. Woo HY, Kim YS, Kang NI, Chung WC, Song CH, Choi IW, et al. Mechanism for acute oral desensitization to antibiotics. Allergy. 2006;61:954-8.
104. Eberlein-Konig B, Ullmann S, Thomas P, Przybilla B. Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization. Clin Exp Allergy. 1995;25:704-12.
105. Jutel M, Muller UR, Fricker M, Rihs S, Pichler WJ, Dahinden C. Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils. Clin Exp Allergy. 1996;26:1112-8.
106. Plewako H, Wosinska K, Arvidsson M, Bjorkander J, Skov PS, Håkansson L, et al. Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy. Int Arch Allergy Immunol. 2006;141:346-53.
107. Jutel M, Akdis M, Akdis CA. Histamine, histamine receptors and their role in immune pathology. Clin Exp Allergy. 2009;39:1786-800.
108. Muller UR, Jutel M, Reimers A, Zumkehr J, Huber C, Kriegel C, et al. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J Allergy Clin Immunol. 2008;122:1001-7.
109. Akdis CA, Simons FE. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol. 2006;533:69-76.
110. Meiler F, Zumkehr J, Klunker S, Ruckert B, Akdis CA, Akdis M. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med. 2008;205:2887-98.
111. Bussmann C, Xia J, Allam JP, Maintz L, Bieber T, Novak N. Early markers for protective mechanisms during rush venom immunotherapy. Allergy. 2010;65(12):1558-65.
112. Schmid JM, Wurtzen PA, Dahl R, Hoffmann HJ. Early improvement in basophil sensitivity predicts symptom relief with grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134:741-4.
113. Shamji MH, Layhadi JA, Scadding GW, Cheung DK, Calderon MA, Turka LA et al. Basophil expression of diamine oxidase: A novel biomarker of allergen immunotherapy response. J Allergy Clin Immunol 2014;Nov 22. Published online ahead of print. (doi:10.1016/j.jaci.2014.09.049)
114. Crameri R, Rhyner C. Novel vaccines and adjuvants for allergen-specific immunotherapy. Curr Opin Immunol. 2006;18:761-8.
115. Senti G, Graf N, Haug S, Rüedi N, von Moos S, Sonderegger T, et al. Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol. 2009;124:997-1002.
116. Allam JP, Wurtzen PA, Reinartz M, Winter J, Vrtala S, Chen KW, et al. Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties. J Allergy Clin Immunol. 2010;126:638-45.
117. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med. 2007;204:1757-64.
118. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med. 2007;204:1775-85.
119. McGuirk P, McCann C, Mills KH. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J Exp Med. 2002;195:221-31.
120. Csoka B, Himer L, Selmeczy Z, Vizi ES, Pacher P, Ledent C, et al. Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J. 2008;22:3491-9.
121. Urry Z, Xystrakis E, Richards DF, McDonald J, Sattar Z, Cousins DJ, et al. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25-dihydroxyvitamin D3 abrogates regulatory function. J Clin Invest. 2009;119(2):387-98.
122. Mucida D, Park Y, Kim G, Scott I, Kronenberg M, Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007;317:256-60.
123. Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol. 2001;2:725-31.
124. de Heer HJ, Hammad H, Soullie T, Hijdra D, Vos N, Willart MA, et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med. 2004;200:89-98.
125. Leb VM, Jahn-Schmid B, Kueng HJ, Schmetterer KG, Haiderer D, Neunkirchner A, et al. Modulation of allergen-specific T-lymphocyte function by virus-like particles decorated with HLA class II molecules. J Allergy Clin Immunol. 2009;124:121-8.
126. Schmitz N, Dietmeier K, Bauer M, Maudrich M, Utzinger S, Muntwiler S, et al. Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy. J Exp Med. 2009;206:1941-55.
127. Bartemes KR, Kephart GM, Fox SJ, Kita H. Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 2014;134:671-8.
128. Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2014.
129. Lao-Araya M, Steveling E, Scadding GW, Durham SR, Shamji MH. Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134:1193-5.
130. 2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest. 1996;98:1676-83.
131. Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998;102:98-106.
132. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, et al. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol. 2003;33:1205-14.
133. Suarez-Fueyo A, Ramos T, Galan A, Jimeno L, Wurtzen PA, Marin A. Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation. J Allergy Clin Immunol. 2014;133:130-8. e1-2.
134. Francis JN, Till SJ, Durham SR. Induction of IL-10 + CD4 + CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol. 2003;111:1255-61.
135. Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol. 2005;116:961-8. quiz 9.
136. Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, et al. Relation of CD4 + CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet. 2004;363:608-15.
137. Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT. Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa. J Allergy Clin Immunol. 2008;121:1467-72. 72 e1.
138. Aslam A, Chan H, Warrell DA, Misbah S, Ogg GS. Tracking antigen-specific T-cells during clinical tolerance induction in humans. PLoS One. 2010;5:e11028.
139. Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ, et al. Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med. 2009; : -.
140. Tsai YG, Lai JC, Yang KD, Hung CH, Yeh YJ, Lin CY. Enhanced CD46-induced regulatory T cells suppress allergic inflammation after Dermatophagoides pteronyssinus-specific immunotherapy. J Allergy Clin Immunol. 2014;134:1206-9.
141. Fox EM, Torrero MN, Evans H, Mitre E. Immunologic characterization of 3 murine regimens of allergen-specific immunotherapy. J Allergy Clin Immunol 2014; Oct 2. Published online ahead of print. (doi:10.1016/j.jaci.2014.07.052)
142. Mauri C, Gray D, Mushtaq N, Londei M. Prevention of athritis by interleukin 10-producing B cells. J Exp Med. 2003;197:489-501.
143. Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med. 2004;199:1567-75.
144. Taylor A, Akdis M, Joss A, Akkoç T, Wenig R, Colonna M, et al. IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Clin Immunol. 2007;120:76-83.
145. Taylor A, Verhagen J, Akkoc T, Wenig R, Flory E, Blaser K, et al. IL-10 suppresses CD2-mediated T cell activation via SHP-1. Mol Immunol. 2009;46(4):622-9.
146. Akdis CA, Joss A, Akdis M, Faith A, Blaser K. A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB J. 2000;14:1666-8.
147. Oral HB, Kotenko SV, Yilmaz M, Mani O, Zumkehr J, Blaser K, et al. Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26. Eur J Immunol. 2006;36:380-8.
148. de Waal MR, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991;174:1209-20.
149. Moore KW, de Waal MR, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765.
150. Ito S, Ansari P, Sakatsume M, Dickensheets H, Vazquez N, Donnelly RP, et al. Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood. 1999;93:1456-63.
151. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998;16:137-61.
152. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4 + CD25- naive T cells to CD4 + CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875-86.
153. Huber S, Schramm C, Lehr HA, Mann A, Schmitt S, Becker C, et al. Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4 + CD25+ T cells. J Immunol. 2004;173:6526-31.
154. Klunker S, Chong MM, Mantel PY, Palomares O, Bassin C, Ziegler M, et al. Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells. J Exp Med. 2009;206:2701-15.
155. Custovic A, Simpson BM, Simpson A, Hallam CL, Marolia H, Walsh D, et al. Current mite, cat, and dog allergen exposure, pet ownership, and sensitization to inhalant allergens in adults. J Allergy Clin Immunol. 2003;111:402-7.
156. Jartti T, Burmeister KA, Seroogy CM, Jennens-Clough ML, Tisler CJ, Salazar LP, et al. Association between CD4(+)CD25(high) T cells and atopy in children. J Allergy Clin Immunol. 2007;120:177-83.
157. Maggi L, Santarlasci V, Liotta F, Frosali F, Angeli R, Cosmi L, et al. Demonstration of circulating allergen-specific CD4 + CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals. J Allergy Clin Immunol. 2007;120:429-36.
158. Orihara K, Narita M, Tobe T, Akasawa A, Ohya Y, Matsumoto K, et al. Circulating Foxp3 + CD4+ cell numbers in atopic patients and healthy control subjects. J Allergy Clin Immunol. 2007;120:960-2.
159. Karlsson MR, Rugtveit J, Brandtzaeg P. Allergen-responsive CD4 + CD25+ regulatory T cells in children who have outgrown cow's milk allergy. J Exp Med. 2004;199:1679-88.
160. Wambre E, DeLong JH, James EA, Torres-Chinn N, Pfützner W, Möbs C, et al. Specific immunotherapy modifies allergen-specific CD4(+) T-cell responses in an epitope-dependent manner. J Allergy Clin Immunol. 2014;133:872-9.
161. Zaleska A, Eiwegger T, Soyer O, van de Veen W, Rhyner C, Soyka MB, et al. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014;69:1162-70.
162. Gorelik M, Narisety SD, Guerrerio AL, Chichester KL, Keet CA, Bieneman AP, et al. Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol 2014; Dec 24. Published online ahead of print. (doi:10.1016/j.jaci.2014.11.010)
163. Kucuksezer UC, Palomares O, Ruckert B, Jartti T, Puhakka T, Nandy A, et al. Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen-specific T-cell tolerance in human tonsils and peripheral blood. J Allergy Clin Immunol. 2013;131:875-85.
164. Palomares O, Rückert B, Jartti T, Kücüksezer UC, Puhakka T, Gomez E, et al. Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance. J Allergy Clin Immunol. 2012;129:510-20.
165. Jartti T, Palomares O, Waris M, Tastan O, Nieminen R, Puhakka T, et al. Distinct regulation of tonsillar immune response in virus infection. Allergy. 2014;69:658-67.
166. van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Söllner S, Akdis DG, et al. IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131:1204-12.
167. Stanic B, van de Veen W, Wirz OF, Rückert B, Morita H, Söllner S, et al. IL-10-overexpressing B cells regulate innate and adaptive immune responses. J Allergy Clin Immunol. 2014;135(3):771-780.e8.
168. Van Ree R, Van Leeuwen WA, Dieges PH, Van Wijk RG, De Jong N, Brewczyski PZ, et al. Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin Exp Allergy. 1997;27:68-74.
169. Gleich GJ, Zimmermann EM, Henderson LL, Yunginger JW. Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Immunol. 1982;70:261-71.
170. Bousquet J, Maasch H, Martinot B, Hejjaoui A, Wahl R, Michel FB. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy. J Allergy Clin Immunol. 1988;82:439-46.
171. Golden DB, Meyers DA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Clinical relevance of the venom-specific immunoglobulin G antibody level during immunotherapy. J Allergy Clin Immunol. 1982;69:489-93.
172. Müller UR, Helbling A, Bischof M. Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy. 1989;44:412-8.
173. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116:608-13.
174. Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, König F, et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol. 2005;116:347-54.
175. Wachholz PA, Durham SR. Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol. 2004;4:313-8.
176. Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J Allergy Clin Immunol. 2004;113:1025-34. quiz 35.
177. Shamji MH, Francis JN, Wurtzen PA, Lund K, Durham SR, Till SJ. Cell-free detection of allergen-IgE cross-linking with immobilized phase CD23: inhibition by blocking antibody responses after immunotherapy. J Allergy Clin Immunol. 2013;132:1003-5. e1-4.
178. Aalberse RC, Schuurman J. IgG4 breaking the rules. Immunology. 2002;105:9-19.
179. van der Neut KM, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, et al. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science. 2007;317:1554-7.
180. Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M. Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy. 2008;63:1455-63.
181. Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dörner T, et al. Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol. 2006;6:741-50.
182. Akdis CA, Akdis M. Mechanisms of immune tolerance to allergens: role of IL-10 and Tregs. J Clin Invest. 2014;124:4678-80.