Immunological mechanisms for desensitization and tolerance in food allergy

Seminars in Immunopathology

Volumn 34, Issue 5, 2012, Pages 689-702

  Rachid, Rima ^a,b   Umetsu, Dale T ^a,b  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Desensitization; Food allergy; Immunotherapy; Tolerance

Indexed keywords

BIOLOGICAL MARKER; FOOD ALLERGEN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G4; OMALIZUMAB;

ALLERGIC DISEASE; ANTIBODY PRODUCTION; B LYMPHOCYTE; BASOPHIL; CELL ACTIVATION; CELL EXPANSION; CELL LOSS; CLINICAL EVALUATION; CLINICAL PROTOCOL; CLONAL ANERGY; DESENSITIZATION; DISEASE ACTIVITY; EGG; FOOD ALLERGY; FOOD INTAKE; HAZELNUT; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; INNATE IMMUNITY; INTESTINE MUCOSA; KIWIFRUIT; MAINTENANCE DRUG DOSE; MAINTENANCE THERAPY; MAST CELL; MILK; MOUTH MUCOSA; ORAL IMMUNOTHERAPY; PEACH; PEANUT; PREVALENCE; PRIORITY JOURNAL; PROVOCATION TEST; REGULATORY T LYMPHOCYTE; REVIEW; SUBCUTANEOUS IMMUNOTHERAPY; SUBLINGUAL IMMUNOTHERAPY; T LYMPHOCYTE; TH1 CELL; TH2 CELL; TREATMENT DURATION; TREATMENT RESPONSE; UPREGULATION;

ADULT; ALLERGENS; ANIMALS; DESENSITIZATION, IMMUNOLOGIC; FOOD HYPERSENSITIVITY; HUMANS; IMMUNOGLOBULIN G; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TH2 CELLS;

EID: 84866128928     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-012-0333-9     Document Type: Review

References (126)

1. Sicherer SH, Sampson HA (2010) Food allergy. J Allergy Clin Immunol 125:S116-125
2. Branum AM, Lukacs SL (2008) Food allergy among U.S. children: Trends in prevalence and hospitalizations. NCHS Data Brief: 1-8
3. Lee LA, Burks AW (2006) Food allergies: Prevalence, molecular characterization, and treatment/prevention strategies. Annu Rev Nutr 26:539-565
4. Sicherer SH, Munoz-Furlong A, Sampson HA (2003) Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: A 5-year follow-up study. J Allergy Clin Immunol 112:1203-1207
5. Grundy J, Matthews S, Bateman B, Dean T, Arshad SH (2002) Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts. J Allergy Clin Immunol 110:784-789
6. Skripak JM, Matsui EC, Mudd K, Wood RA (2007) The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol 120:1172-1177
7. Jarvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA (2007) Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy. Allergy 62:758-765
8. Skolnick HS, Conover-Walker MK, Koerner CB, Sampson HA, Burks W, Wood RA (2001) The natural history of peanut allergy. J Allergy Clin Immunol 107:367-374
9. Bock SA, Munoz-Furlong A, Sampson HA (2001) Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 107:191-193
10. Bock SA, Munoz-Furlong A, Sampson HA (2007) Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 119:1016-1018
11. Sicherer SH, Noone SA, Munoz-Furlong A (2001) The impact of childhood food allergy on quality of life. Ann Allergy Asthma Immunol 87:461-464
12. Cummings AJ, Knibb RC, King RM, Lucas JS (2010) The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: A review. Allergy 65:933-945
13. Sicherer SH, Furlong TJ, DeSimone J, Sampson HA (2001) The US Peanut and Tree Nut Allergy Registry: Characteristics of reactions in schools and day care. J Pediatr 138:560-565
14. Furlong TJ, DeSimone J, Sicherer SH (2001) Peanut and tree nut allergic reactions in restaurants and other food establishments. J Allergy Clin Immunol 108:867-870
15. Boyano-Martinez T, Garcia-Ara C, Pedrosa M, Diaz-Pena JM, Quirce S (2009) Accidental allergic reactions in children allergic to cow's milk proteins. J Allergy Clin Immunol 123:883-888
16. Vander Leek TK, Liu AH, Stefanski K, Blacker B, Bock SA (2000) The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. J Pediatr 137:749-755
17. Akdis CA, Akdis M (2011) Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 127:18-27, quiz 8-9
18. Fujita H, Soyka MB, Akdis M, Akdis CA (2012) Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy 2:2
19. Nelson HS, Lahr J, Rule R, Bock A, Leung D (1997) Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol 99:744-751
20. Fernandez-Rivas M, Garrido Fernandez S, Nadal JA, Diaz de Durana MD, Garcia BE, Gonzalez-Mancebo E, Martin S, Barber D, Rico P, Tabar AI (2009) Randomized double-blind, placebocontrolled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy 64:876-883
21. Pereira C, Bartolome B, Asturias JA, Ibarrola I, Tavares B, Loureiro G, Machado D, Chieira C (2009) Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: A case report. Cases J 2:6553
22. Garcia BE, Gonzalez-Mancebo E, Barber D, Martin S, Tabar AI, Diaz de Durana AM, Garrido-Fernandez S, Salcedo G, Rico P, Fernandez-Rivas M. Sublingual immunotherapy in peach allergy: Monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen. J Investig Allergol Clin Immunol 20: 514-520
23. Kerzl R, Simonowa A, Ring J, Ollert M, Mempel M (2007) Lifethreatening anaphylaxis to kiwi fruit: Protective sublingual allergen immunotherapy effect persists even after discontinuation. J Allergy Clin Immunol 119:507-8
24. Mempel M, Rakoski J, Ring J, Ollert M (2003) Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful sublingual allergen immunotherapy. J Allergy Clin Immunol 111:1406-9
25. Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R, Castello JV, Alonso R, de Mateo JA, Cerda-Trias T, San Miguel-Moncin Mdel M, Monzon S, Garcia M, Palacios R, Cistero-Bahima A (2005) Sublingual immunotherapy for hazelnut food allergy: A randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol 116:1073-9
26. Kim EH, Bird JA, Kulis M, Laubach S, Pons L, Shreffler W, Steele P, Kamilaris J, Vickery B, Burks AW. Sublingual immunotherapy for peanut allergy: Clinical and immunologic evidence of desensitization. J Allergy Clin Immunol 127: 640-6e1
27. Enrique E, Malek T, Pineda F, Palacios R, Bartra J, Tella R, Basagana M, Alonso R, Cistero-Bahima A (2008) Sublingual immunotherapy for hazelnut food allergy: A follow-up study. Ann Allergy Asthma Immunol 100:283-4
28. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, Steele P, Driggers S, Burks AW, Wood RA. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 129: 448-55, 55 e1-5
29. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, Hiegel A, Kamilaris J, Carlisle S, Yue X, Kulis M, Pons L, Vickery B, Burks AW. A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol 127: 654-660
30. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124(292-300):e1-97
31. Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG (2004) A protocol for oral desensitization in children with IgEmediated cow's milk allergy. Allergy 59:980-7
32. Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW (2009) Successful oral tolerance induction in severe peanut allergy. Allergy 64:1218-20
33. Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT. Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy. J Allergy Clin Immunol 127: 1622-1624
34. Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A (2008) Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol 121:343-7
35. Itoh N, Itagaki Y, Kurihara K. Rush specific oral tolerance induction in school-age children with severe egg allergy: One year follow up. Allergol Int 59: 43-51
36. Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, Steele PH, Pons L, Helm RM, Lee LA, Burks AW (2007) Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 119:199-205
37. Staden U, Blumchen K, Blankenstein N, Dannenberg N, Ulbricht H, Dobberstein K, Ziegert M, Niggemann B, Wahn U, Beyer K (2008) Rush oral immunotherapy in children with persistent cow's milk allergy. J Allergy Clin Immunol 122:418-9
38. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, de Oliveira LC, Shreffler WG, Sampson HA, Niggemann B, Wahn U, Beyer K. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 126: 83-91 e1
39. Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow's milk epicutaneous immunotherapy in children: A pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol 125: 1165-1167
40. Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA (2008) A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 122:1154-60
41. Vickery BP, Pons L, Kulis M, Steele P, Jones SM, Burks AW. Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol 105: 444-450
42. Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K (2007) Specific oral tolerance induction in food allergy in children: Efficacy and clinical patterns of reaction. Allergy 62:1261-1269
43. Rolinck-Werninghaus C, Staden U, Mehl A, Hamelmann E, Beyer K, Niggemann B (2005) Specific oral tolerance induction with food in children: Transient or persistent effect on food allergy? Allergy 60:1320-1322
44. Vickery BP, Burks W. Oral immunotherapy for food allergy. Curr Opin Pediatr 22: 765-770
45. Nadeau KC, Kohli A, Iyengar S, DeKruyff RH, Umetsu DT. Oral immunotherapy and anti-IgE antibody-adjunctive treatment for food allergy. Immunol Allergy Clin North Am 32: 111-133
46. Nowak-Wegrzyn A, Sampson HA. Future therapies for food allergies. J Allergy Clin Immunol 127: 558-573; quiz 74-75
47. Meglio P, Giampietro PG, Gianni S, Galli E (2008) Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy -follow-up at 4 yr and 8 months. Pediatr Allergy Immunol 19:412-419
48. Vickery BP, Pons L, Kulis M, Steele P, Jones SM, Burks AW (2010) Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol 105:444-450
49. Blumchen K, Ulbricht H, Staden U, Dobberstein K, Beschorner J, de Oliveira LC, Shreffler WG, Sampson HA, Niggemann B, Wahn U, Beyer K (2010) Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 126(83-91):e1
50. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, Steele P, Driggers S, Burks AW, Wood RA (2012) The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 129:448-455, 55 e1-5
51. Varshney P, Steele PH, Vickery BP, Bird JA, Thyagarajan A, Scurlock AM, Perry TT, Jones SM, Burks AW (2009) Adverse reactions during peanut oral immunotherapy home dosing. J Allergy Clin Immunol 124:1351-1352
52. Lack G Update on risk factors for food allergy. J Allergy Clin Immunol 129: 1187-1197
53. Larche M, Akdis CA, Valenta R (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6:761-771
54. Berin MC, Shreffler WG (2008) T(H)2 adjuvants: Implications for food allergy. J Allergy Clin Immunol 121:1311-1320, quiz 21-2
55. Chatila TA, Li N, Garcia-Lloret M, Kim HJ, Nel AE (2008) T-cell effector pathways in allergic diseases: Transcriptional mechanisms and therapeutic targets. J Allergy Clin Immunol 121:812-823, quiz 24-5
56. Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, Ramon M, Bergman R, Krueger JG, Guttman-Yassky E (2009) 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 123:1244-1252, e2
57. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA (2003) IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205-1214
58. Francis JN, Till SJ, Durham SR (2003) Induction of IL-10 + CD4 + CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol 111:1255-1261
59. Akdis M, Blaser K, Akdis CA (2005) T regulatory cells in allergy: Novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol 116:961-968, quiz 9
60. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA (2010) Role of Treg in immune regulation of allergic diseases. Eur J Immunol 40:1232-1240
61. Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, Viola A, Odom S, Rivera J, Colombo MP, Pucillo CE (2008) CD4 + CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 29:771-781
62. Kearley J, Barker JE, Robinson DS, Lloyd CM (2005) Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4 + CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med 202:1539-1547
63. Kearley J, Robinson DS, Lloyd CM (2008) CD4 + CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling. J Allergy Clin Immunol 122:617-624, e6
64. Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M (2008) Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy 63:1455-1463
65. Lin W, Truong N, Grossman WJ, Haribhai D, Williams CB, Wang J, Martin MG, Chatila TA (2005) Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 116:1106-1115
66. Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM (2000) JM2, encoding a fork headrelated protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106:R75-81
67. Josefowicz SZ, Niec RE, Kim HY, Treuting P, Chinen T, Zheng Y, Umetsu DT, Rudensky AY. Extrathymically generated regulatory T cells control mucosal TH2 inflammation. Nature 482: 395-399
68. Duan W, So T, Mehta AK, Choi H, Croft M (2011) Inducible CD4 + LAP + Foxp3-regulatory T cells suppress allergic inflammation. J Immunol 187:6499-6507
69. Mucida D, Kutchukhidze N, Erazo A, Russo M, Lafaille JJ, Curotto de Lafaille MA (2005) Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest 115:1923-1933
70. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov, II, Umesaki Y, Itoh K, Honda K. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337-41
71. Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT (2008) Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa. J Allergy Clin Immunol 121:1467-1472, 72 e1
72. Allam JP, Wurtzen PA, Reinartz M, Winter J, Vrtala S, Chen KW, Valenta R, Wenghoefer M, Appel T, Gros E, Niederhagen B, Bieber T, Lund K, Novak N (2010) 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 126:638-645, e1
73. Taylor A, Akdis M, Joss A, Akkoc T, Wenig R, Colonna M, Daigle I, Flory E, Blaser K, Akdis CA (2007) IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Clin Immunol 120:76-83
74. Marshall JS, Leal-Berumen I, Nielsen L, Glibetic M, Jordana M (1996) Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. J Clin Invest 97:1122-1128
75. Schandene L, Alonso-Vega C, Willems F, Gerard C, Delvaux A, Velu T, Devos R, de Boer M, Goldman M (1994) B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 152:4368-4374
76. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) 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 198:1875-1886
77. Liu YJ (2006) Thymic stromal lymphopoietin: Master switch for allergic inflammation. J Exp Med 203:269-273
78. Lee EB, Kim KW, Hong JY, Jee HM, Sohn MH, Kim KE (2010) Increased serum thymic stromal lymphopoietin in children with atopic dermatitis. Pediatr Allergy Immunol 21:e457-460
79. Siracusa MC, Saenz SA, Hill DA, Kim BS, Headley MB, Doering TA, Wherry EJ, Jessup HK, Siegel LA, Kambayashi T, Dudek EC, KuboM, Cianferoni A, Spergel JM, Ziegler SF, Comeau MR, Artis D. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 477: 229-233
80. Zhu Z, Oh MH, Yu J, Liu YJ, Zheng T (2011) The role of TSLP in IL-13-induced atopic march. Sci Rep 1:23
81. Pushparaj PN, Tay HK, H'Ng SC, Pitman N, Xu D, McKenzie A, Liew FY, Melendez AJ (2009) The cytokine interleukin-33 mediates anaphylactic shock. Proc Natl Acad Sci U S A 106:9773-9778
82. Koyasu S, Moro K, Tanabe M, Takeuchi T (2010) Natural helper cells: A new player in the innate immune response against helminth infection. Adv Immunol 108:21-44
83. Koyasu S, Moro K (2011) Innate Th2-type immune responses and the natural helper cell, a newly identified lymphocyte population. Curr Opin Allergy Clin Immunol 11:109-114
84. Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE, Dekruyff RH, Umetsu DT. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol 12: 631-638
85. Allakhverdi Z, Comeau MR, Jessup HK, Delespesse G (2009) Thymic stromal lymphopoietin as a mediator of crosstalk between bronchial smooth muscles and mast cells. J Allergy Clin Immunol 123(958-60):e2
86. Van Ree R, Van Leeuwen WA, Dieges PH, Van Wijk RG, De Jong N, Brewczyski PZ, Kroon AM, Schilte PP, Tan KY, Simon-Licht IF, Roberts AM, Stapel SO, Aalberse RC (1997) Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin Exp Allergy 27:68-74
87. Gleich GJ, Zimmermann EM, Henderson LL, Yunginger JW (1982) Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: A six-year prospective study. J Allergy Clin Immunol 70:261-271
88. Eberlein-Konig B, Ullmann S, Thomas P, Przybilla B (1995) Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization. Clin Exp Allergy 25:704-712
89. Jutel M, Muller UR, Fricker M, Rihs S, Pichler WJ, Dahinden C (1996) Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils. Clin Exp Allergy 26:1112-1118
90. Plewako H, Wosinska K, Arvidsson M, Bjorkander J, Skov PS, Hakansson L, Rak S (2006) Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy. Int Arch Allergy Immunol 141:346-353
91. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, Hiegel A, Kamilaris J, Carlisle S, Yue X, Kulis M, Pons L, Vickery B, Burks AW (2011) A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol 127:654-660
92. Bedoret D, Singh AK, Shaw V, Hoyte EG, Hamilton R, Dekruyff RH, Schneider LC, Nadeau KC, Umetsu DT. Changes in antigenspecific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab. Mucosal Immunol 5: 267-276
93. Scadding G, Durham S (2009) Mechanisms of sublingual immunotherapy. J Asthma 46:322-334
94. Allam JP, Peng WM, Appel T, Wenghoefer M, Niederhagen B, Bieber T, Berge S, Novak N (2008) Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells. J Allergy Clin Immunol 121:368-374, e1
95. Allam JP, Novak N, Fuchs C, Asen S, Berge S, Appel T, Geiger E, Kochan JP, Bieber T (2003) Characterization of dendritic cells from human oral mucosa: A new Langerhans' cell type with high constitutive FcepsilonRI expression. J Allergy Clin Immunol 112:141-148
96. Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, Staple SQ, Aalberse RC, Till SJ, Durham SR (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252-3259
97. Zemann B, Schwaerzler C, Griot-Wenk M, Nefzger M, Mayer P, Schneider H, de Weck A, Carballido JM, Liehl E (2003) Oral administration of specific antigens to allergy-prone infant dogs induces IL-10 and TGF-beta expression and prevents allergy in adult life. J Allergy Clin Immunol 111:1069-1075
98. Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H (2003) Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18:605-617
99. Bottcher MF, Jenmalm MC (2002) Breastfeeding and the development of atopic disease during childhood. Clin Exp Allergy 32:159-161
100. Scadding GW, Shamji MH, Jacobson MR, Lee DI, Wilson D, Lima MT, Pitkin L, Pilette C, Nouri-Aria K, Durham SR. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergenspecific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin Exp Allergy 40: 598-606
101. Kulis M, Saba K, Kim EH, Bird JA, Kamilaris N, Vickery BP, Staats H, Burks AW. Increased peanut-specific IgA levels in saliva correlate with food challenge outcomes after peanut sublingual immunotherapy. J Allergy Clin Immunol 129: 1159-1162
102. Itoh N, Itagaki Y, Kurihara K (2010) Rush specific oral tolerance induction in school-age children with severe egg allergy: One year follow up. Allergol Int 59:43-51
103. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O (2005) Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 116:608-613
104. Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V (2005) Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 116:347-354
105. Golden DB, Meyers DA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM (1982) Clinical relevance of the venomspecific immunoglobulin G antibody level during immunotherapy. J Allergy Clin Immunol 69:489-93
106. Muller U, Helbling A, Bischof M (1989) Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy 44:412-418
107. Schroeder HW Jr, Cavacini L (2010) Structure and function of immunoglobulins. J Allergy Clin Immunol 125:S41-52
108. Wachholz PA, Durham SR (2004) Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol 4:313-318
109. Till SJ, Francis JN, Nouri-Aria K, Durham SR (2004) Mechanisms of immunotherapy. J Allergy Clin Immunol 113:1025-1034, quiz 35
110. Uermosi C, Beerli RR, Bauer M, Manolova V, Dietmeier K, Buser RB, Kundig TM, Saudan P, Bachmann MF (2010) Mechanisms of allergen-specific desensitization. J Allergy Clin Immunol 126:375-383
111. Carballido JM, Carballido-Perrig N, Kagi MK, Meloen RH, Wuthrich B, Heusser CH, Blaser K (1993) T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2. J Immunol 150:3582-3591
112. Shreffler WG, Wanich N, Moloney M, Nowak-Wegrzyn A, Sampson HA (2009) Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein. J Allergy Clin Immunol 123:43-52, e7
113. Weiner HL (2000) Oral tolerance, an active immunologic process mediated by multiple mechanisms. J Clin Invest 106:935-7
114. Hoyne GF, Tan K, Corsin-Jimenez M,Wahl K, Stewart M, Howie SE, Lamb JR (2000) Immunological tolerance to inhaled antigen. Am J Respir Crit Care Med 162:S169-174
115. Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT (2011) Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy. J Allergy Clin Immunol 127:1622-1624
116. MacGlashan DW Jr, Bochner BS, Adelman DC, Jardieu PM, Togias A, McKenzie-White J, Sterbinsky SA, Hamilton RG, Lichtenstein LM (1997) Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 158:1438-1445
117. Stone KD, Prussin C, Metcalfe DD (2010) IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 125:S73-80
118. Kitaura J, Song J, Tsai M, Asai K, Maeda-Yamamoto M, Mocsai A, Kawakami Y, Liu FT, Lowell CA, Barisas BG, Galli SJ, Kawakami T (2003) Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI. Proc Natl Acad Sci U S A 100:12911-12916
119. Corren J, Shapiro G, Reimann J, Deniz Y, Wong D, Adelman D, Togias A (2008) Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy. J Allergy Clin Immunol 121:506-511
120. Noga O, Hanf G, Kunkel G (2003) Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol 131:46-52
121. Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, Larosa DF, Renner ED, Orange JS, Bushman FD, Artis D (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18:538-546
122. Turcanu V, Maleki SJ, Lack G (2003) Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts. J Clin Invest 111:1065-1072
123. Nagata S, McKenzie C, Pender SL, Bajaj-Elliott M, Fairclough PD, Walker-Smith JA, Monteleone G, MacDonald TT (2000) Human Peyer's patch T cells are sensitized to dietary antigen and display a Th cell type 1 cytokine profile. J Immunol 165:5315-5321
124. Faria AM, Weiner HL (2005) Oral tolerance. Immunol Rev 206:232-59
125. Meiler F, Zumkehr J, Klunker S, Ruckert B, Akdis CA, Akdis M (2008) In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J Exp Med 205:2887-2898
126. Aslam A, Chan H, Warrell DA, Misbah S, Ogg GS. Tracking antigen-specific T-cells during clinical tolerance induction in humans. PLoS One 5: E11028