Tolerizing allergic responses in the lung

Mucosal Immunology

Volumn 3, Issue 4, 2010, Pages 334-344

  Lloyd, C M ^a   Murdoch, J R ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIALLERGIC AGENT; COLECALCIFEROL; DEXAMETHASONE; IMMUNOGLOBULIN E; INTERLEUKIN 10; PLACEBO; TRANSFORMING GROWTH FACTOR BETA;

ANAPHYLAXIS; ANTIGEN SPECIFICITY; ASTHMA; CD4+ T LYMPHOCYTE; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; ENVIRONMENTAL EXPOSURE; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOTHERAPY; LUNG FUNCTION; NONHUMAN; PERINATAL PERIOD; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW;

EID: 77953735780     PISSN: 19330219     EISSN: None     Source Type: Journal    
DOI: 10.1038/mi.2010.19     Document Type: Review

References (164)

1. Levy, O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat. Rev. Immunol. 7, 379-390 (2007).
2. Harju, K., Glumoff, V. & Hallman, M. Ontogeny of Toll-like receptors Tlr2 and Tlr4 in mice. Pediatr. Res. 49, 81-83 (2001).
3. Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259-1260 (1989).
4. Wills-Karp, M., Santeliz, J. & Karp, C. L. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat. Rev. Immunol. 1, 69-75 (2001).
5. Martinez, F. D. Viruses and atopic sensitization in the fi rst years of life. Am. J. Respir. Crit. Care Med. 162, S95-S99 (2000).
6. Holt, P. G., Upham, J. W. & Sly, P. D. Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies. J. Allergy Clin. Immunol. 116, 16-24 (2005).
7. Kusel, M. M. et al. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J. Allergy Clin. Immunol. 119, 1105-1110 (2007).
8. Hollingsworth, J. W. et al. In utero supplementation with methyl donors enhances allergic airway disease in mice. J. Clin. Invest. 118, 3462-3469 (2008).
9. Patel, M. M. & Miller, R. L. Air pollution and childhood asthma: recent advances and future directions. Curr. Opin. Pediatr. 21, 235-242 (2009).
10. Litonjua, A. A. & Weiss, S. T. Is vitamin D defi ciency to blame for the asthma epidemic? J. Allergy Clin. Immunol. 120, 1031-1035 (2007).
11. Devereux, G. Early life events in asthma-diet. Pediatr. Pulmonol. 42, 663-673 (2007).
12. Ege, M. J. et al. Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in schoolage children. J. Allergy Clin. Immunol. 117, 817-823 (2006).
13. Gerhold, K. et al. Prenatal initiation of endotoxin airway exposure prevents subsequent allergen-induced sensitization and airway infl ammation in mice. J. Allergy Clin. Immunol. 118, 666-673 (2006).
14. Polte, T., Hennig, C. & Hansen, G. Allergy prevention starts before conception: maternofetal transfer of tolerance protects against the development of asthma. J. Allergy Clin. Immunol. 122, 1022-1030 (2008).
15. Devereux, G. The increase in the prevalence of asthma and allergy: food for thought. Nat. Rev. Immunol. 6, 869-874 (2006).
16. Willers, S. M. et al. Maternal food consumption during pregnancy and the longitudinal development of childhood asthma. Am. J. Respir. Crit Care Med. 178, 124-131 (2008).
17. Miller, R. L. Prenatal maternal diet affects asthma risk in offspring. J. Clin. Invest. 118, 3265-3268 (2008).
18. Verhasselt, V. et al. Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat. Med. 14, 170-175 (2008).
19. Hammad, H. & Lambrecht, B. N. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat. Rev. Immunol. 8, 193-204 (2008). (Pubitemid 351323293)
20. Jiang, A. et al. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27, 610-624 (2007).
21. Gribar, S. C., Richardson, W. M., Sodhi, C. P. & Hackam, D. J. No longer an innocent bystander: epithelial toll-like receptor signaling in the development of mucosal infl ammation. Mol. Med. 14, 645-659 (2008).
22. Barrett, N. A. & Austen, K. F. Innate cells and T helper 2 cell immunity in airway infl ammation. Immunity 31, 425-437 (2009).
23. Lan, R. S., Stewart, G. A. & Henry, P. J. Role of protease-activated receptors in airway function: a target for therapeutic intervention? Pharmacol. Ther. 95, 239-257 (2002).
24. Haagsman, H. P., Hogenkamp, A., van, E. M. & Veldhuizen, E. J. Surfactant collectins and innate immunity. Neonatology 93, 288-294 (2008).
25. Kurowska-Stolarska, M. et al. IL-33 induces antigen-specifi c IL-5+ T cells and promotes allergic-induced airway infl ammation independent of IL-4. J. Immunol. 181, 4780-4790 (2008).
26. Rank, M. A. et al. IL-33-activated dendritic cells induce an atypical TH2- type response. J. Allergy Clin. Immunol. 123, 1047-1054 (2009).
27. Ballantyne, S. J. et al. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J. Allergy Clin. Immunol. 120, 1324-1331 (2007).
28. Kato, A. & Schleimer, R. P. Beyond infl ammation: airway epithelial cells are at the interface of innate and adaptive immunity. Curr. Opin. Immunol. 19, 711-720 (2007).
29. Lee, J. Y. et al. Murine thymic stromal lymphopoietin promotes the differentiation of regulatory T cells from thymic CD4(+)CD8(+)CD25(+) naive cells in a dendritic cell-independent manner. Immunol. Cell Biol. 86, 206-213 (2008).
30. Kouzaki, H., O ' Grady, S. M., Lawrence, C. B. & Kita, H. Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2. J. Immunol. 183, 1427-1434 (2009).
31. Corrigan, C. J. et al. Early production of thymic stromal lymphopoietin precedes infi ltration of dendritic cells expressing its receptor in allergeninduced late phase cutaneous responses in atopic subjects. Allergy 64, 1014-1022 (2009).
32. Lambrecht, B. N. & Hammad, H. Lung dendritic cells: targets for therapy in allergic disease. Handb. Exp. Pharmacol. 99-114 (2009).
33. de Heer, H. J. et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 200, 89-98 (2004).
34. Jakubzick, C. et al. Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J. Exp. Med. 205, 2839-2850 (2008).
35. Hammad, H. et al. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat. Med. 15, 410-416 (2009).
36. Trompette, A. et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585-588 (2009).
37. Phipps, S. et al. Toll/IL-1 signaling is critical for house dust mite-specifi c helper T cell type 2 and type 17 [corrected] responses. Am. J. Respir. Crit. Care Med. 179, 883-893 (2009).
38. Nathan, A. T., Peterson, E. A., Chakir, J. & Wills-Karp, M. Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. J. Allergy Clin. Immunol. 123, 612-618 (2009).
39. Ebeling, C. et al. Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway infl ammation and airway hyperresponsiveness through different pathways. J. Allergy Clin. Immunol. 115, 623-630 (2005).
40. Takizawa, T. et al. Abrogation of bronchial eosinophilic infl ammation and attenuated eotaxin content in protease-activated receptor 2-defi cient mice. J. Pharmacol. Sci. 98, 99-102 (2005).
41. Kauffman, H., Tamm, M., Timmerman, J. A. & Borger, P. House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms. Clin. Mol. Allergy 4, 5 (2006).
42. Mantovani, A., Sica, A. & Locati, M. Macrophage polarization comes of age. Immunity 23, 344-346 (2005).
43. Wynn, T. A. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat. Rev. Immunol. 4, 583-594 (2004).
44. Bedoret, D. et al. Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J. Clin. Invest. 119, 3723-3738 (2009).
45. Sato, K. et al. Type II alveolar cells play roles in macrophage-mediated host innate resistance to pulmonary mycobacterial infections by producing proinfl ammatory cytokines. J. Infect. Dis. 185, 1139-1147 (2002).
46. Takabayshi, K. et al. Induction of a homeostatic circuit in lung tissue by microbial compounds. Immunity 24, 475-487 (2006).
47. Morris, D. G. et al. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature 422, 169-173 (2003).
48. Gardai, S. J. et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance infl ammation. Cell 115, 13-23 (2003).
49. Snelgrove, R. J. et al. A critical function for CD200 in lung immune homeostasis and the severity of infl uenza infection. Nat. Immunol. 9, 1074-1083 (2008).
50. Holt, P. G., Batty, J. E. & Turner, K. J. Inhibition of specifi c IgE responses in mice by pre-exposure to inhaled antigen. Immunology 42, 409-417 (1981).
51. Ostroukhova, M. et al. Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J. Clin. Invest. 114, 28-38 (2004).
52. Akbari, O. et al. Antigen-specifi c regulatory T cells develop via the ICOSICOS- ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat. Med. 8, 1024-1032 (2002).
53. Lloyd, C. M. & Hawrylowicz, C. M. Regulatory T cells in asthma. Immunity 31, 438-449 (2009).
54. Hawrylowicz, C. M. & O ' Garra, A. Potential role of interleukin-10- secreting regulatory T cells in allergy and asthma. Nat. Rev. Immunol. 5, 271-283 (2005).
55. Kearley, J., Barker, J. E., Robinson, D. S. & Lloyd, C. M. Resolution of airway infl ammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J. Exp. Med. 202, 1539-1547 (2005).
56. Kearley, J., Robinson, D. S. & Lloyd, C. M. CD4+CD25+ regulatory T cells reverse established allergic airway infl ammation and prevent airway remodeling. J. Allergy Clin. Immunol. 122, 617-624 (2008).
57. Lewkowich, I. P. et al. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J. Exp. Med. 202, 1549-1561 (2005).
58. Leech, MD, Benson, R. A., De Vries, A., Fitch, P. M. & Howie, S. E. Resolution of Der p1-induced allergic airway infl ammation is dependent on CD4+CD25+Foxp3+ regulatory cells. J. Immunol. 179, 7050-7058 (2007). Ref Type: Generic.
59. Strickland, D. H. et al. Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells. J. Exp. Med. 203, 2649-2660 (2006).
60. Campbell, J. D. et al. Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J. Exp. Med. 206, 1535-1547 (2009).
61. Sather, B. D. et al. Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specifi c infl ammatory disease. J. Exp. Med. 204, 1335-1347 (2007).
62. Stock, P. et al. Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity. Nat. Immunol. 5, 1149-1156 (2004).
63. Stock, P. et al. CD8(+) T cells regulate immune responses in a murine model of allergen-induced sensitization and airway infl ammation. Eur. J. Immunol. 34, 1817 - 1827 (2004).
64. Korsgren, M. et al. Natural killer cells determine development of allergeninduced eosinophilic airway infl ammation in mice. J. Exp. Med. 189, 553-562 (1999).
65. Singh, A. et al. Regulatory role of B cells in a murine model of allergic airway disease. J. Immunol. 180, 7318-7326 (2008).
66. Moon, T. C. et al. Advances in mast cell biology: new understanding of heterogeneity and function. Mucosal Immunol. 3, 111 - 128 (2010).
67. Ozdemir, C., Akdis, M. & Akdis, C. A. T regulatory cells and their counterparts: masters of immune regulation. Clin. Exp. Allergy 39, 626-639 (2009).
68. Boismenu, R. & Havran, W. L. Gammadelta T cells in host defense and epithelial cell biology. Clin. Immunol. Immunopathol. 86, 121-133 (1998).
69. Lahn, M. et al. Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells. Nat. Med. 5, 1150-1156 (1999).
70. Zuany-Amorim, C. et al. Requirement for gammadelta T cells in allergic airway infl ammation. Science 280, 1265-1267 (1998).
71. Chien, Y. H. & Konigshofer, Y. Antigen recognition by gammadelta T cells. Immunol. Rev. 215, 46-58 (2007).
72. Crowley, M. P. et al. A population of murine gammadelta T cells that recognize an inducible MHC class Ib molecule. Science 287, 314-316 (2000).
73. Groh, V., Steinle, A., Bauer, S. & Spies, T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 279, 1737-1740 (1998).
74. Jin, N. et al. Mismatched antigen prepares gamma delta T cells for suppression of airway hyperresponsiveness. J. Immunol. 174, 2671-2679 (2005).
75. Pietschmann, K. et al. Toll-like receptor expression and function in subsets of human gammadelta T lymphocytes. Scand. J. Immunol. 70, 245-255 (2009).
76. Wands, J. M. et al. Distribution and leukocyte contacts of gammadelta T cells in the lung. J. Leukoc. Biol. 78, 1086-1096 (2005).
77. Scotet, E., Nedellec, S., Devilder, M. C., Allain, S. & Bonneville, M. Bridging innate and adaptive immunity through gammadelta T-dendritic cell crosstalk. Front Biosci. 13, 6872-6885 (2008).
78. Dieli, F. et al. Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response. Eur. J. Immunol. 34, 3227-3235 (2004).
79. Kirby, A. C., Newton, D. J., Carding, S. R. & Kaye, P. M. Pulmonary dendritic cells and alveolar macrophages are regulated by gammadelta T cells during the resolution of S. pneumoniae-induced infl ammation. J. Pathol. 212, 29-37 (2007).
80. Jameson, J. & Havran, W. L. Skin gammadelta T-cell functions in homeostasis and wound healing. Immunol. Rev. 215, 114-122 (2007).
81. Huber, S. A., Born, W. & O ' Brien, R. Dual functions of murine gammadelta cells in infl ammation and autoimmunity in coxsackievirus B3-induced myocarditis: role of Vgamma1+ and Vgamma4+ cells. Microbes. Infect. 7, 537-543 (2005).
82. Andrew, E. M. & Carding, S. R. Murine gammadelta T cells in infections: benefi cial or deleterious? Microbes. Infect. 7, 529-536 (2005).
83. Carding, S. R. & Egan, P. J. Gammadelta T cells: functional plasticity and heterogeneity. Nat. Rev. Immunol. 2, 336-345 (2002).
84. Taniguchi, M., Seino, K. & Nakayama, T. The NKT cell system: bridging innate and acquired immunity. Nat. Immunol. 4, 1164-1165 (2003).
85. Bendelac, A., Savage, P. B. & Teyton, L. The biology of NKT cells. Annu. Rev. Immunol. 25, 297-336 (2007).
86. Akbari, O. et al. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat. Med. 9, 582-588 (2003).
87. Parekh, V. V. et al. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 115, 2572-2583 (2005).
88. Matangkasombut, P. et al. Natural killer T cells in the lungs of patients with asthma. J. Allergy Clin. Immunol. 123, 1181-1185 (2009).
89. Singh, A. M., Moore, P. E., Gern, J. E., Lemanske, R. F. Jr. & Hartert, T. V. Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am. J. Respir. Crit. Care Med. 175, 108-119 (2007).
90. Lemanske, J. & BUSSE, W. W. Asthma: factors underlying inception, exacerbation, and disease progression. J. Allergy Clin. Immunol. 117, S456-S461 (2006).
91. Jackson, D. J. et al. Wheezing rhinovirus illnesses in early life predict asthma development in high risk children. Am. J. Respir. Crit. Care Med. 178, 667-672 (2008).
92. Pala, P. et al. Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy. Eur. Respir. J. 20, 376-382 (2002).
93. Behera, A. K., Kumar, M., Lockey, R. F. & Mohapatra, S. S. 2- 5 Oligoadenylate synthetase plays a critical role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells. J. Biol. Chem. 277, 25601-25608 (2002).
94. Svartengren, M., Strand, V., Bylin, G., Jarup, L. & Pershagen, G. Shortterm exposure to air pollution in a road tunnel enhances the asthmatic response to allergen. Eur. Respir. J. 15, 716-724 (2000).
95. McCreanor, J. et al. Respiratory effects of exposure to diesel traffi c in persons with asthma. N. Engl. J. Med. 357, 2348-2358 (2007).
96. Morgenstern, V. et al. Atopic diseases, allergic sensitization, and exposure to traffi c-related air pollution in children. Am. J. Respir. Crit. Care Med. 177, 1331-1337 (2008).
97. Dong, C. C. et al. Effect of diesel exhaust particles on allergic reactions and airway responsiveness in ovalbumin-sensitized brown Norway rats. Toxicol. Sci. 88, 202-212 (2005).
98. Sagai, M., Furuyama, A. & Ichinose, T. Biological effects of diesel exhaust particles (DEP). III. Pathogenesis of asthma like symptoms in mice. Free Radic. Biol. Med. 21, 199-209 (1996).
99. de Haar, C., Hassing, I., Bol, M., Bleumink, R., Pieters, R. Ultrafi ne carbon black particles cause early airway infl ammation and have adjuvant activity in a mouse allergic airway disease model. Toxicol Sci. 87, 409-418 (2005).
100. Diaz-Sanchez, D., Tsien, A., Fleming, J. & Saxon, A. Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specifi c IgE and skews cytokine production to a T helper cell 2-type pattern. J. Immunol. 158, 2406-2413 (1997).
101. Hao, M., Comier, S., Wang, M., Lee, J. J. & Nel, A. Diesel exhaust particles exert acute effects on airway infl ammation and function in murine allergen provocation models. J. Allergy Clin. Immunol. 112, 905-914 (2003).
102. Holgate, S. T., Roberts, G., Arshad, H. S., Howarth, P. H. & Davies, D. E. The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis. Proc. Am. Thorac. Soc. 6, 655-659 (2009).
103. Cookson, W. The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat. Rev. Immunol. 4, 978-988 (2004).
104. Bisgaard, H. et al. Childhood asthma after bacterial colonization of the airway in neonates. N. Engl. J. Med. 357, 1487-1495 (2007).
105. Kraft, M. The role of bacterial infections in asthma. Clin. Chest Med. 21, 301-313 (2000).
106. Sethi, S., Evans, N., Grant, B. J. & Murphy, T. F. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N. Engl. J. Med. 347, 465-471 (2002). (Pubitemid 34879333)
107. Blasi, F., Johnston, S.L. The role of antibiotics in asthma. Int. J. Anti. Age. 29, 485-493 (2007).
108. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N. Engl. J. Med. 355, 2226-2235 (2006).
109. Phelan, P. D., Robertson, C. F. & Olinsky, A. The Melbourne Asthma Study: 1964 - 1999. J. Allergy Clin. Immunol. 109, 189 - 194 (2002).
110. Morgan, W. J. et al. Outcome of asthma and wheezing in the fi rst 6 years of life: follow-up through adolescence. Am. J. Respir. Crit. Care Med. 172, 1253-1258 (2005).
111. Saglani, S. et al. Early detection of airway wall remodeling and eosinophilic infl ammation in preschool wheezers. Am. J. Respir. Crit Care Med. 176, 858-864 (2007).
112. Kicic, A., Sutanto, E. N., Stevens, P. T., Knight, D. A. & Stick, S. M. Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma. Am. J. Respir. Crit. Care Med. 174, 1110-1118 (2006).
113. Till, S. J., Francis, J. N., Nouri-Aria, K. & Durham, S. R. Mechanisms of immunotherapy. J. Allergy Clin. Immunol. 113, 1025-1034 (2004).
114. Pajno, G. B., Barberio, G., De, L. F., Morabito, L. & Parmiani, S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specifi c immunotherapy. A six-year follow-up study. Clin. Exp. Allergy 31, 1392-1397 (2001).
115. Moller, C. et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J. Allergy Clin. Immunol. 109, 251-256 (2002).
116. Jacobsen, L. et al. Specifi c immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 62, 943-948 (2007).
117. Kim, D. S. & Drake-Lee, A. B. Allergen immunotherapy in ENT: historical perspective. J. Laryngol. Otol. 117, 940-945 (2003).
118. Durham, S. R. et al. Long-term clinical effi cacy of grass-pollen immunotherapy. N. Engl. J. Med. 341, 468-475 (1999).
119. Valenta, R. The future of antigen-specifi c immunotherapy of allergy. Nat. Rev. Immunol. 2, 446-453 (2002).
120. Bilo, M. B. et al. The VISYT trial: venom immunotherapy safety and tolerability with purifi ed vs. nonpurifi ed extracts. Ann. Allergy Asthma Immunol. 103, 57-61 (2009).
121. Jacobsen, L. & Valovirta, E. How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Curr. Opin. Allergy Clin. Immunol. 7, 556-560 (2007).
122. Ebner, C. et al. Immunological changes during specifi c immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specifi c for Phl p 1, a major grass pollen allergen. Clin. Exp. Allergy 27, 1007 - 1015 (1997).
123. Gardner, L. M., Spyroglou, L., O ' Hehir, R. E. & Rolland, J. M. Increased allergen concentration enhances IFN-gamma production by allergic donor T cells expressing a peripheral tissue traffi cking phenotype. Allergy 59, 1308-1317 (2004).
124. Bellinghausen, I. et al. Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur. J. Immunol. 27, 1131-1139 (1997).
125. Wachholz, P. A., Soni, N. K., Till, S. J. & Durham, S. R. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J. Allergy Clin. Immunol. 112, 915-922 (2003).
126. Wachholz, P. A. & Durham, S. R. Induction of " blocking " IgG antibodies during immunotherapy. Clin. Exp. Allergy 33, 1171-1174 (2003).
127. Akdis, M. & Akdis, C. A. Therapeutic manipulation of immune tolerance in allergic disease. Nat. Rev. Drug Discov. 8, 645-660 (2009).
128. Francis, J. N. et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J. Allergy Clin. Immunol. 121, 1120-1125 (2008).
129. Jutel, M. et al. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specifi c immunotherapy. Eur. J. Immunol. 33, 1205-1214 (2003).
130. Francis, J. N., Till, S. J. & Durham, S. R. Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J. Allergy Clin. Immunol. 111, 1255-1261 (2003).
131. Nouri-Aria, K. T. et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J. Immunol. 172, 3252-3259 (2004).
132. Jeannin, P., Lecoanet, S., Delneste, Y., Gauchat, J. F. & Bonnefoy, J. Y. IgE versus IgG4 production can be differentially regulated by IL-10. J. Immunol. 160, 3555-3561 (1998).
133. Stavnezer, J. & Kang, J. The surprising discovery that TGF beta specifi cally induces the IgA class switch. J. Immunol. 182, 5-7 (2009).
134. O ' Hehir, R. E. et al. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. Am. J. Respir. Crit Care Med. 180, 936-947 (2009).
135. Challacombe, S. J. & Tomasi, T. B. Jr. Systemic tolerance and secretory immunity after oral immunization. J. Exp. Med. 152, 1459-1472 (1980).
136. Taylor, B. et al. Transient IgA defi ciency and pathogenesis of infantile atopy. Lancet 2, 111-113 (1973).
137. Scadding, G. W. et al. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specifi c immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin. Exp. Allergy (2010).
138. Pilette, C. et al. Grass pollen immunotherapy induces an allergenspecifi c IgA2 antibody response associated with mucosal TGF-beta expression. J. Immunol. 178, 4658-4666 (2007).
139. van Oosterhout, A. J. et al. Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma. Am. J. Respir. Cell Mol. Biol. 19, 622-628 (1998).
140. Vissers, J. L. et al. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J. Allergy Clin. Immunol. 113, 1204-1210 (2004).
141. Kapsenberg, M. L. Dendritic-cell control of pathogen-driven T-cell polarization. Nat. Rev. Immunol. 3, 984-993 (2003).
142. Akbari, O., DeKruyff, R. H. & Umetsu, D. T. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat. Immunol. 2, 725-731 (2001).
143. Weiner, H. L. The mucosal milieu creates tolerogenic dendritic cells and T(R)1 and T(H)3 regulatory cells. Nat. Immunol. 2, 671-672 (2001).
144. Fallarino, F. et al. Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J. Immunol. 173, 3748-3754 (2004).
145. Belladonna, M. L. et al. Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J. Immunol. 177, 130-137 (2006).
146. Munn, D. H. et al. Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science 297, 1867 - 1870 (2002).
147. Taher, Y. A. et al. Indoleamine 2, 3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model. J. Allergy Clin. Immunol. 121, 983-991 (2008).
148. Janssen, E. M., Wauben, M. H., Nijkamp, F. P., van, E. W. & van Oosterhout, A. J. Immunomodulatory effects of antigen-pulsed macrophages in a murine model of allergic asthma. Am. J. Respir. Cell Mol. Biol. 27, 257-264 (2002).
149. Janssen, E. M., van Oosterhout, A. J., Nijkamp, F. P., van, E. W. & Wauben, M. H. The effi cacy of immunotherapy in an experimental murine model of allergic asthma is related to the strength and site of T cell activation during immunotherapy. J. Immunol. 165, 7207-7214 (2000).
150. Pajno, G. B. Sublingual immunotherapy: the optimism and the issues. J. Allergy Clin. Immunol. 119, 796-801 (2007).
151. Van, O. L. et al. IL-10-inducing adjuvants enhance sublingual immunotherapy effi cacy in a murine asthma model. Int. Arch. Allergy Immunol. 145, 152-162 (2008).
152. Taher, Y. A., van Esch, B. C., Hofman, G. A., Henricks, P. A. & van Oosterhout, A. J. 1alpha, 25-dihydroxyvitamin D3 potentiates the benefi cial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta. J. Immunol. 180, 5211-5221 (2008).
153. Passalacqua, G., Guerra, L., Pasquali, M., Lombardi, C. & Canonica, G. W. Effi cacy and safety of sublingual immunotherapy. Ann. Allergy Asthma Immunol. 93, 3-12 (2004).
154. Pajno, G. B. et al. Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial. Allergy 59, 883-887 (2004).
155. Valovirta, E., Passalacqua, G. & Canonica, W. G. Non-injection routes for immunotherapy of allergic diseases. Clin. Allergy Immunol. 18, 607-623 (2004).
156. Dahl, R. et al. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefi t with progressive immunologic changes over 2 years. J. Allergy Clin. Immunol. 121, 512-518 (2008).
157. Compalati, E., Penagos, M., Tarantini, F., Passalacqua, G. & Canonica, G. W. Specifi c immunotherapy for respiratory allergy: state of the art according to current meta-analyses. Ann. Allergy Asthma Immunol. 102, 22-28 (2009).
158. Pipet, A., Botturi, K., Pinot, D., Vervloet, D. & Magnan, A. Allergenspecifi c immunotherapy in allergic rhinitis and asthma. Mechanisms and proof of effi cacy. Respir. Med. 103, 800-812 (2009).
159. Cuburu, N. et al. Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 25, 8598-8610 (2007).
160. Mascarell, L. et al. Mapping of the lingual immune system reveals the presence of both regulatory and effector CD4+ T cells. Clin. Exp. Allergy 39, 1910 - 1919 (2009).
161. Calderon, M. A. et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst. Rev. 1, CD001936 (2007).
162. Larche, M. & Wraith, D. C. Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat. Med. 11, S69-S76 (2005).
163. Haselden, B. M., Kay, A. B. & Larche, M. Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitopeinduced late asthmatic reactions. J. Exp. Med. 189, 1885 - 1894 (1999).
164. Verhoef, A., Alexander, C., Kay, A. B. & Larche, M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2, e78 (2005).