Publikationsserver der Universitätsbibliothek Marburg
Titel:Zelluläre Mechanismen der Toleranzinduktion unter spezifischer Immuntherapie mit inhalativen Allergenen
Autor:Möbs, Christian
Weitere Beteiligte: Pfützner, Wolfgang (Dr.)
Veröffentlicht:2010
URI:https://archiv.ub.uni-marburg.de/diss/z2010/0354
URN: urn:nbn:de:hebis:04-z2010-03545
DOI: https://doi.org/10.17192/z2010.0354
DDC: Medizin
Titel (trans.):Cellular mechanisms of tolerance induction by specific immunotherapy with inhalative allergens
Publikationsdatum:2010-07-08
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Specific immunotherapy, T cells, spezifische Immuntherapie, Antikörper, Allergy, Antibodies, T-Zellen, Desensibilisierung, Allergie
Referenziert von:

Zusammenfassung:
Die Inzidenz respiratorischer Allergien hat in den letzten Jahrzehnten vor allem in den westlich geprägten Industriestaaten kontinuierlich zugenommen. Das wesentliche Merkmal einer Überempfindlichkeitsreaktion gegen Aeroallergene ist die Produktion allergenspezifischer IgE-Antikörper, die rezeptorvermittelt an Effektorzellen der allergischen Entzündung gebunden werden. Durch Allergenkontakt kommt es zur Quervernetzung der auf der Oberfläche von basophilen und eosinophilen Granulozyten oder Mastzellen gebundenen IgE-Antikörper mit konsekutiver Zellaktivierung und Freisetzung von Histamin sowie weiterer proinflammatorischer Mediatoren. Diese Entzündungsmediatoren führen schließlich zu IgE-vermittelten Typ-I-Reaktionen. Seit fast einem Jahrhundert wird die spezifische Immuntherapie (SIT), auch Hypo- oder Desensibilisierung genannt, zur Behandlung von Typ-I-Reaktionen eingesetzt. Nach wie vor stellt die SIT die einzige, kausale Behandlungsform dar, die in der Lage ist, den natürlichen Krankheitsverlauf von Soforttypallergikern zu beeinflussen. In zahlreichen klinischen Studien wurde neben der kurativen Wirksamkeit auch der präventive Nutzen einer SIT bei der Behandlung allergischer Atemwegserkrankungen belegt. Allerdings sind die der SIT zugrunde liegenden immunologischen Mechanismen, die zur Induktion und Aufrechterhaltung immunologischer Allergentoleranz führen, noch nicht abschließend aufgeklärt. In der vorliegenden Studie wurde der Einfluss der SIT auf zelluläre und humorale Immunparameter in einem Kollektiv von 15 Birkenpollenallergikern über den Verlauf einer dreijährigen Therapie mit Birkenpollenextrakt untersucht und vergleichend Kontrollpopulationen mit ausschließlich symptomatisch therapierten Birkenpollenallergikern und gesunden Probanden ohne Manifestation einer IgE-vermittelten Allergie gegenübergestellt. Ein wesentliches Ergebnis dieser Arbeit ist der Nachweis, dass die SIT-vermittelte Toleranzinduktion eine ausgeprägte zeitliche Dynamik aufweist. So sind verschiedene zelluläre und humorale Faktoren phasenabhängig in unterschiedlichem Maße an der Wiederherstellung und Aufrechterhaltung allergenspezifischer Toleranz beteiligt. Klinisch führte die SIT bei allen in die Studie eingeschlossenen Patienten bereits in der ersten Pollenflugsaison nach Therapiebeginn zu einer signifikanten Reduktion und im weiteren Behandlungsverlauf zur anhaltenden Verbesserung allergischer Beschwerden. Entsprechende Veränderungen der allergischen Reaktionsfähigkeit konnte dagegen durch eine ausschließlich symptomatische Medikation nicht erreicht werden. Die Analysen allergenspezifischer T-Zellfrequenzen zeigten sequentielle, durch die SIT induzierte Veränderungen mit einer frühzeitigen, im weiteren Verlauf jedoch transienten Induktion Bet v 1-spezifischer Typ-1-regulatorischer T (Tr1)-Zellen. Die größte Tr1-Zellzunahme fand sich im ersten Jahr der Therapie während der natürlichen Allergenexposition, gleichzeitig zum typischen Anstieg allergenspezifischer T-Helfer (Th) 2-Zellen in der Birkenpollensaison. In Kokultivierungsversuchen konnte die supprimierende Aktivität der Tr1-Zellen nachgewiesen werden, welche über IL-10-abhängige Mechanismen vermittelt wurde und in direkter Abhängigkeit zur ihrer Zellzahl stand. Dagegen zeigte die Frequenz Foxp3+ regulatorischer T-Zellen, ermittelt durch das Expressionsmuster der Oberflächenmarker CD4, CD25 und CD127, weder während saisonaler Allergenexposition noch durch die SIT induzierte Veränderungen. Bemerkenswert waren auch die durch die SIT vermittelten Modifikationen allergenspezifischer Th-Zellen. So kam es in den SIT-therapierten Patienten gegen Ende des ersten Behandlungsjahres zu einer Verschiebung der Th2-dominierten zu einer Th1-mediierten Immunantwort. Es zeigte sich somit im ersten Behandlungsjahr eine ausgeprägte Dynamik bei den Bet v 1-spezifischen T-Zellsubpopulationen. Allerdings ließen sich im weiteren Verlauf der SIT auch zu Zeiten natürlicher Pollenexposition nur noch reduzierte Frequenzen allergenspezifischer T-Zellen detektieren, möglicherweise die Folge einer Induktion peripherer T-Zelltoleranz. Der Einfluss der SIT auf die humorale Immunantwort war durch bereits ab dem dritten Behandlungsmonat kontinuierlich zunehmende Serumspiegel birkenpollenspezifischer IgG4-Antikörper gekennzeichnet. Eine ähnliche Induktion spezifischer IgG4-Antikörper konnte in der ausschließlich symptomatisch behandelten sowie der gesunden Kontrollpopulation nicht festgestellt werden. Im Gegensatz dazu fanden sich bei den allergenspezifischen IgE- und IgA-Antikörperkonzentrationen keine Unterschiede zwischen den drei Probandenkollektiven. Die im Rahmen dieser Arbeit erhobenen Daten zeigen somit, dass die SIT-vermittelte Toleranzinduktion bei Typ-I-Allergien auf differenzierten, multifaktoriellen immunregulatorischen Mechanismen beruht.

Bibliographie / References

  1. Nocentini, G., and Riccardi, C. (2005). GITR: a multifaceted regulator of immunity belonging to the tumor necrosis factor receptor superfamily. Eur J Immunol 35, 1016-1022.
  2. Wilczynski, J. R., Radwan, M., and Kalinka, J. (2008). The characterization and role of regulatory T cells in immune reactions. Front Biosci 13, 2266-2274.
  3. Kalesnikoff, J., Huber, M., Lam, V., Damen, J. E., Zhang, J., Siraganian, R. P., and Krystal, G. (2001). Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 14, 801-811.
  4. Schmidt-Weber, C. B., Akdis, M., and Akdis, C. A. (2007). TH17 cells in the big picture of immunology. J Allergy Clin Immunol 120, 247-254.
  5. Passalacqua, G., and Canonica, G. W. (2002). Long-lasting clinical efficacy of allergen specific immunotherapy. Allergy 57, 275-276.
  6. Royer, B., Varadaradjalou, S., Saas, P., Guillosson, J. J., Kantelip, J. P., and Arock, M. (2001). Inhibition of IgE-induced activation of human mast cells by IL-10. Clin Exp Allergy 31, 694-704.
  7. Snijders, A., Kalinski, P., Hilkens, C. M., and Kapsenberg, M. L. (1998). High-level IL-12 production by human dendritic cells requires two signals. Int Immunol 10, 1593-1598.
  8. Kisselgof, A. B., and Oettgen, H. C. (1998). The expression of murine B cell CD23, in vivo, is regulated by its ligand, IgE. Int Immunol 10, 1377-1384.
  9. Senna, G., Ridolo, E., Calderon, M., Lombardi, C., Canonica, G. W., and Passalacqua, G. (2009). Evidence of adherence to allergen-specific immunotherapy. Curr Opin Allergy Clin Immunol 9, 544-548.
  10. Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy. Clin Exp Allergy 37, 564-571.
  11. van Ree, R., and Yazdanbakhsh, M. (2007). Allergic disorders in African countries: linking immunology to accurate phenotype. Allergy 62, 237-246.
  12. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. Bmj 302, 265-269.
  13. Senti, G., Graf, N., Haug, S., Ruedi, N., von Moos, S., Sonderegger, T., Johansen, P., and Kundig, T. M. (2009). Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol 124, 997-1002.
  14. Ozdemir, C., Akdis, M., and Akdis, C. A. (2009). T regulatory cells and their counterparts: masters of immune regulation. Clin Exp Allergy 39, 626-639.
  15. Niggemann, B., Jacobsen, L., Dreborg, S., Ferdousi, H. A., Halken, S., Host, A., Koivikko, A., Koller, D., Norberg, L. A., Urbanek, R., et al. (2006). Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy 61, 855-859.
  16. Jacobsen, L., Niggemann, B., Dreborg, S., Ferdousi, H. A., Halken, S., Host, A., Koivikko, A., Norberg, L. A., Valovirta, E., Wahn, U., and Moller, C. (2007). Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 62, 943-948.
  17. Van Overtvelt, L., Wambre, E., Maillere, B., von Hofe, E., Louise, A., Balazuc, A. M., Bohle, B., Ebo, D., Leboulaire, C., Garcia, G., and Moingeon, P. (2008). Assessment of Bet v 1- specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers. J Immunol 180, 4514-4522.
  18. Pereira-Santos, M. C., Baptista, A. P., Melo, A., Alves, R. R., Soares, R. S., Pedro, E., Pereira- Barbosa, M., Victorino, R. M., and Sousa, A. E. (2008). Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom immunotherapy. Clin Exp Allergy 38, 291-297.
  19. Van Ree, R., Van Leeuwen, W. A., Dieges, P. H., Van Wijk, R. G., De Jong, N., Brewczyski, P. Z., Kroon, A. M., Schilte, P. P., Tan, K. Y., Simon-Licht, I. F., et al. (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.
  20. Novembre, E., Galli, E., Landi, F., Caffarelli, C., Pifferi, M., De Marco, E., Burastero, S. E., Calori, G., Benetti, L., Bonazza, P., et al. (2004). Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 114, 851-857.
  21. Visco, V., Dolecek, C., Denepoux, S., Le Mao, J., Guret, C., Rousset, F., Guinnepain, M. T., Kraft, D., Valenta, R., Weyer, A., et al. (1996). Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1. J Immunol 157, 956-962.
  22. Riechelmann, H., Bachert, C., Goldschmidt, O., Hauswald, B., Klimek, L., Schlenter, W. W., Tasman, A. J., and Wagenmann, M. (2003). [Application of the nasal provocation test on diseases of the upper airways. Position paper of the German Society for Allergology and Clinical Immunology (ENT Section) in cooperation with the Working Team for Clinical Immunology]. Laryngorhinootologie 82, 183-188.
  23. Szabo, S. J., Sullivan, B. M., Peng, S. L., and Glimcher, L. H. (2003). Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 21, 713-758.
  24. Wachholz, P. A., and Durham, S. R. (2004). Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol 4, 313-318.
  25. Tiemessen, M. M., Van Hoffen, E., Knulst, A. C., Van Der Zee, J. A., Knol, E. F., and Taams, L. S. (2002). CD4 CD25 regulatory T cells are not functionally impaired in adult patients with IgE-mediated cow's milk allergy. J Allergy Clin Immunol 110, 934-936.
  26. Rak, S., Heinrich, C., Jacobsen, L., Scheynius, A., and Venge, P. (2001). A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol 108, 921-928.
  27. Parronchi, P., Macchia, D., Piccinni, M. P., Biswas, P., Simonelli, C., Maggi, E., Ricci, M., Ansari, A. A., and Romagnani, S. (1991). Allergen-and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production.
  28. King, T. P., Hoffman, D., Lowenstein, H., Marsh, D. G., Platts-Mills, T. A., and Thomas, W. (1994). Allergen nomenclature. WHO/IUIS Allergen Nomenclature Subcommittee. Int Arch Allergy Immunol 105, 224-233.
  29. Shim, J. Y., Kim, B. S., Cho, S. H., Min, K. U., and Hong, S. J. (2003). Allergen-specific conventional immunotherapy decreases immunoglobulin E-mediated basophil histamine releasability. Clin Exp Allergy 33, 52-57.
  30. Jutel, M., Jaeger, L., Suck, R., Meyer, H., Fiebig, H., and Cromwell, O. (2005). Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 116, 608-613.
  31. Khattri, R., Cox, T., Yasayko, S. A., and Ramsdell, F. (2003). An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 4, 337-342.
  32. Wheeler, A. (2006). A novel adjuvant complex, tyrosine-MPL, for prophylactic and therapeutic vaccines. Vaccine 24 Suppl 2, S2-40-41.
  33. McCutcheon, M., Wehner, N., Wensky, A., Kushner, M., Doan, S., Hsiao, L., Calabresi, P., Ha, T., Tran, T. V., Tate, K. M., et al. (1997). A sensitive ELISPOT assay to detect low- frequency human T lymphocytes. J Immunol Methods 210, 149-166.
  34. Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein. J Allergy Clin Immunol 123, 43-52 e47.
  35. Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion molecule-1 expression, and the infiltration of eosinophils, macrophages, and T cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Immunol 158, 5050-5057.
  36. Schandene, L., Alonso-Vega, C., Willems, F., Gerard, C., Delvaux, A., Velu, T., Devos, R., de Boer, M., and Goldman, M. (1994). B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 152, 4368-4374.
  37. Macfarlane, A. J., Kon, O. M., Smith, S. J., Zeibecoglou, K., Khan, L. N., Barata, L. T., McEuen, A. R., Buckley, M. G., Walls, A. F., Meng, Q., et al. (2000). Basophils, eosinophils, and mast cells in atopic and nonatopic asthma and in late-phase allergic reactions in the lung and skin. J Allergy Clin Immunol 105, 99-107.
  38. Jutel, M., Pichler, W. J., Skrbic, D., Urwyler, A., Dahinden, C., and Muller, U. R. (1995). Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. J Immunol 154, 4187-4194.
  39. Scholl, I., Kopp, T., Bohle, B., and Jensen-Jarolim, E. (2006). Biodegradable PLGA particles for improved systemic and mucosal treatment of Type I allergy. Immunol Allergy Clin North Am 26, 349-364.
  40. van Neerven, R. J., Wikborg, T., Lund, G., Jacobsen, B., Brinch-Nielsen, A., Arnved, J., and Ipsen, H. (1999). Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 163, 2944-2952.
  41. Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155, 1151-1164.
  42. Liu, W., Putnam, A. L., Xu-Yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., Fazekas de St Groth, B., et al. (2006). CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203, 1701-1711.
  43. Wurtzen, P. A., Lund, L., Lund, G., Holm, J., Millner, A., and Henmar, H. (2007). Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity. Int Arch Allergy Immunol 144, 287-295.
  44. Rodriguez, J., Crespo, J. F., Lopez-Rubio, A., De La Cruz-Bertolo, J., Ferrando-Vivas, P., Vives, R., and Daroca, P. (2000). Clinical cross-reactivity among foods of the Rosaceae family. J Allergy Clin Immunol 106, 183-189.
  45. Radbruch, A., Muehlinghaus, G., Luger, E. O., Inamine, A., Smith, K. G., Dorner, T., and Hiepe, F. (2006). Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6, 741-750.
  46. Vieths, S., Scheurer, S., and Ballmer-Weber, B. (2002). Current understanding of cross- reactivity of food allergens and pollen. Ann N Y Acad Sci 964, 47-68.
  47. Wosinska-Becler, K., Plewako, H., Hakansson, L., and Rak, S. (2004). Cytokine production in peripheral blood cells during and outside the pollen season in birch-allergic patients and non-allergic controls. Clin Exp Allergy 34, 123-130.
  48. Pierkes, M., Bellinghausen, I., Hultsch, T., Metz, G., Knop, J., and Saloga, J. (1999). Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-gamma production of T cells. J Allergy Clin Immunol 103, 326-332.
  49. Kimura, I., Tanizaki, Y., Goda, Y., Komagoe, H., and Kitani, H. (1985). Decrease in reactivity of basophils by immunotherapy with housedust extract. Clin Allergy 15, 1-7.
  50. Traidl-Hoffmann, C., Jakob, T., and Behrendt, H. (2009). Determinants of allergenicity. J Allergy Clin Immunol 123, 558-566.
  51. Dexamethasone inhibits maturation, cytokine production and Fc epsilon RI expression of human cord blood-derived mast cells. Clin Exp Allergy 32, 906-913.
  52. Janssen, O., Stocker, A., Sanzenbacher, R., Oberg, H. H., Siddiqi, M. A., and Kabelitz, D. (2000). Differential regulation of activation-induced cell death in individual human T cell clones. Int Arch Allergy Immunol 121, 183-193.
  53. Stassen, M., Jonuleit, H., Muller, C., Klein, M., Richter, C., Bopp, T., Schmitt, S., and Schmitt, E. (2004). Differential regulatory capacity of CD25+ T regulatory cells and preactivated CD25+ T regulatory cells on development, functional activation, and proliferation of Th2 cells. J Immunol 173, 267-274.
  54. Karmaus, W., and Botezan, C. (2002). Does a higher number of siblings protect against the development of allergy and asthma? A review. J Epidemiol Community Health 56, 209- 217.
  55. Yilmaz-Demirdag, Y., Prather, B., and Bahna, S. L. (2009). Does heredity determine the allergy manifestation or the sensitisation to a specific allergen? Allergol Immunopathol (Madr).
  56. Luttmann, W., Dauer, E., Schmidt, S., Marx, O., Hossfeld, M., Matthys, H., and Virchow, J. C., Jr. (2000). Effects of interferon-gamma and tumour necrosis factor-alpha on CD95/Fas ligand-mediated apoptosis in human blood eosinophils. Scand J Immunol 51, 54-59.
  57. Ozdemir, C., Yazi, D., Gocmen, I., Yesil, O., Aydogan, M., Semic-Jusufagic, A., Bahceciler, N. N., and Barlan, I. B. (2007). Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite-allergic children with asthma. Pediatr Allergy Immunol 18, 508-515.
  58. Stephens, G. L., McHugh, R. S., Whitters, M. J., Young, D. A., Luxenberg, D., Carreno, B. M., Collins, M., and Shevach, E. M. (2004). Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J Immunol 173, 5008-5020.
  59. Rossi, R. E., Monasterolo, G., Coco, G., Silvestro, L., and Operti, D. (2007). Evaluation of serum IgG4 antibodies specific to grass pollen allergen components in the follow up of allergic patients undergoing subcutaneous and sublingual immunotherapy. Vaccine 25, 957-964.
  60. Stern, D. A., Riedler, J., Nowak, D., Braun-Fahrlander, C., Swoboda, I., Balic, N., Chen, K. W., Vrtala, S., Gronlund, H., van Hage, M., et al. (2007). Exposure to a farming environment has allergen-specific protective effects on TH2-dependent isotype switching in response to common inhalants. J Allergy Clin Immunol 119, 351-358.
  61. Riedler, J., Braun-Fahrlander, C., Eder, W., Schreuer, M., Waser, M., Maisch, S., Carr, D., Schierl, R., Nowak, D., and von Mutius, E. (2001). Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129-1133.
  62. Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., et al. (2006). Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203, 1693-1700.
  63. van der Veen, M. J., Mulder, M., Witteman, A. M., van Ree, R., Aalberse, R. C., Jansen, H. M., and van der Zee, J. S. (1996). False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens. J Allergy Clin Immunol 98, 1028-1034.
  64. Mantel, P. Y., Kuipers, H., Boyman, O., Rhyner, C., Ouaked, N., Ruckert, B., Karagiannidis, C., Lambrecht, B. N., Hendriks, R. W., Crameri, R., et al. (2007). GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol 5, e329.
  65. Zhu, J., Yamane, H., Cote-Sierra, J., Guo, L., and Paul, W. E. (2006). GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res 16, 3-10.
  66. Karagiannidis, C., Akdis, M., Holopainen, P., Woolley, N. J., Hense, G., Ruckert, B., Mantel, P. Y., Menz, G., Akdis, C. A., Blaser, K., and Schmidt-Weber, C. B. (2004). Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol 114, 1425-1433.
  67. Walker, S. M., Varney, V. A., Gaga, M., Jacobson, M. R., and Durham, S. R. (1995). Grass pollen immunotherapy: efficacy and safety during a 4-year follow-up study. Allergy 50, 405-413.
  68. Strachan, D. P. (1989). Hay fever, hygiene, and household size. Bmj 299, 1259-1260.
  69. Aeroallergens. 2007; – World Immune Regulation Meeting (WIRM) I 2007, Davos C. Möbs, C. Slotosch, C. Veldman, H. Löffler and M. Hertl Cellular and humoral mechanisms of tolerance induction on specific immunotherapy (SIT) with birch pollen allergens. 2008; Exp Dermatol, 17(3):243 (P008) – XXXV. Jahrestagung der Arbeitsgemeinschaft Dermatologische Forschung e.V. (ADF) 2008, Erlangen Möbs Christian, Slotosch Caroline, Veldman Christian, Löffler Harald, Hertl Michael Induction of Bet v 1-specific T regulatory cells and IgG4 antibodies by specific immunotherapy (SIT) with birch pollen allergens. 2008; – World Immune Regulation Meeting (WIRM) II 2008, Davos Möbs Christian, Slotosch Caroline, Löffler Harald, Hertl Michael, Pfützner Wolfgang Humoral and cellular mechanisms of tolerance induction in patients treated by specific immunotherapy (SIT) with birch pollen allergen. 2008; – 11 th German Meeting on Th1/Th2 research 2008, Marburg Schriftenverzeichnis C. Möbs, C. Slotosch, H. Löffler, M. Hertl and W. Pfützner Impact of specific immunotherapy and environmental birch pollen exposure on Bet v 1-specific humoral and cellular profiles in birch pollen allergics and healthy individuals. 2009; Exp Dermatol, 18(3):277 (P013) – XXXVI. Jahrestagung der Arbeitsgemeinschaft Dermatologische Forschung e.V. (ADF) 2009, Heidelberg Möbs Christian, Slotosch Caroline, Löffler Harald, Hertl Michael, Pfützner Wolfgang Impact of specific immunotherapy and environmental birch pollen exposure on Bet v 1-specific humoral and cellular profiles in birch pollen allergics and healthy individuals. 2009; – World Immune Regulation Meeting (WIRM) III 2009, Davos Christian Möbs, Caroline Slotosch, Harald Löffler, Michael Hertl, Wolfgang Pfützner Mechanismen der Toleranzinduktion bei Typ-I-Allergien. 2009; – ACUTE: Allergy Conference under one Umbrella and Talent Exchange -Workshop 2009, Hohenkammer Möbs C, Slotosch C, Löffler H, Hertl M, Pfützner W Bet v 1-specific immune responses in specific immunotherapy-treated birch pollen allergic individuals during seasonal pollen exposure. 2009; J Invest Dermatol, 129 Suppl 2:S4 (P021) –
  70. Van Parijs, L., and Abbas, A. K. (1998). Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280, 243-248.
  71. Valenta, R., Breiteneder, H., Petternburger, K., Breitenbach, M., Rumpold, H., Kraft, D., and Scheiner, O. (1991). Homology of the major birch-pollen allergen, Bet v I, with the major Literaturverzeichnis pollen allergens of alder, hazel, and hornbeam at the nucleic acid level as determined by cross-hybridization. J Allergy Clin Immunol 87, 677-682.
  72. O'Brien, R. M., Byron, K. A., Varigos, G. A., and Thomas, W. R. (1997). House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes. Clin Exp Allergy 27, 46-51.
  73. Jarolim, E., Rumpold, H., Endler, A. T., Ebner, H., Breitenbach, M., Scheiner, O., and Kraft, D. (1989). IgE and IgG antibodies of patients with allergy to birch pollen as tools to define the allergen profile of Betula verrucosa. Allergy 44, 385-395.
  74. Yamaguchi, M., Lantz, C. S., Oettgen, H. C., Katona, I. M., Fleming, T., Miyajima, I., Kinet, J. P., and Galli, S. J. (1997). IgE enhances mouse mast cell Fc(epsilon)RI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions. J Exp Med 185, 663-672.
  75. Jardieu, P. M., and Fick, R. B., Jr. (1999). IgE inhibition as a therapy for allergic disease. Int Arch Allergy Immunol 118, 112-115.
  76. Jeannin, P., Lecoanet, S., Delneste, Y., Gauchat, J. F., and Bonnefoy, J. Y. (1998). IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 160, 3555-3561.
  77. Strait, R. T., Morris, S. C., and Finkelman, F. D. (2006). IgG-blocking antibodies inhibit IgE- mediated anaphylaxis in vivo through both antigen interception and Fc gamma RIIb cross-linking. J Clin Invest 116, 833-841.
  78. Jutel, M., Akdis, M., Budak, F., Aebischer-Casaulta, C., Wrzyszcz, M., Blaser, K., and Akdis, C. A. (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.
  79. Wu, K., Bi, Y., Sun, K., and Wang, C. (2007). IL-10-producing type 1 regulatory T cells and allergy. Cell Mol Immunol 4, 269-275.
  80. Vieira, P. L., Christensen, J. R., Minaee, S., O'Neill, E. J., Barrat, F. J., Boonstra, A., Barthlott, T., Stockinger, B., Wraith, D. C., and O'Garra, A. (2004). IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 172, 5986-5993.
  81. Wynn, T. A. (2003). IL-13 effector functions. Annu Rev Immunol 21, 425-456.
  82. Roesler, E., Weiss, R., Weinberger, E. E., Fruehwirth, A., Stoecklinger, A., Mostbock, S., Ferreira, F., Thalhamer, J., and Scheiblhofer, S. (2009). Immunize and disappear-safety- optimized mRNA vaccination with a panel of 29 allergens. J Allergy Clin Immunol 124, 1070-1077 e1071-1011.
  83. Romagnani, S. (2004). Immunologic influences on allergy and the TH1/TH2 balance. J Allergy Clin Immunol 113, 395-400.
  84. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995). Immunologic self- tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25).
  85. Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up. Allergy 52, 914-920.
  86. Wang, H., Barrenas, F., Bruhn, S., Mobini, R., and Benson, M. (2009). Increased IFN-gamma activity in seasonal allergic rhinitis is decreased by corticosteroid treatment. J Allergy Clin Immunol 124, 1360-1362.
  87. Yamanaka, K., Yuta, A., Kakeda, M., Sasaki, R., Kitagawa, H., Gabazza, E. C., Okubo, K., Kurokawa, I., and Mizutani, H. (2009). Induction of IL-10-producing regulatory T cells with TCR diversity by epitope-specific immunotherapy in pollinosis. J Allergy Clin Immunol 124, 842-845 e847.
  88. Jonuleit, H., Schmitt, E., Schuler, G., Knop, J., and Enk, A. H. (2000). Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192, 1213-1222.
  89. Jonuleit, H., Schmitt, E., Kakirman, H., Stassen, M., Knop, J., and Enk, A. H. (2002). Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J Exp Med 196, 255-260.
  90. "Infectious" transplantation tolerance. Science 259, 974-977.
  91. Inhibition of receptor-dependent and receptor-independent generation of the respiratory burst in human neutrophils and monocytes by human serum IgA. Pediatr Res 36, 235- 243.
  92. Refaeli, Y., Van Parijs, L., Alexander, S. I., and Abbas, A. K. (2002). Interferon gamma is required for activation-induced death of T lymphocytes. J Exp Med 196, 999-1005.
  93. Roncarolo, M. G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., and Levings, M. K. (2006). Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev 212, 28-50.
  94. Lundgren, M., Persson, U., Larsson, P., Magnusson, C., Smith, C. I., Hammarstrom, L., and Severinson, E. (1989). Interleukin 4 induces synthesis of IgE and IgG4 in human B cells.
  95. Sanderson, C. J. (1992). Interleukin-5, eosinophils, and disease. Blood 79, 3101-3109.
  96. Marshall, J. D., Wen, Y., Abrams, J. S., and Umetsu, D. T. (1993). In vitro synthesis of IL-4 by human CD4+ T cells requires repeated antigenic stimulation. Cell Immunol 152, 18-34.
  97. Literaturverzeichnis allergen components: implications for class switch mechanisms. Eur J Immunol 32, 576- 584.
  98. Romagnani, S. (1994). Lymphokine production by human T cells in disease states. Annu Rev Immunol 12, 227-257.
  99. Christian Möbs, Caroline Slotosch, Harald Löffler, Wolfgang Pfützner, Michael Hertl Cellular and Humoral Mechanisms of Immune Tolerance in Immediate-Type Allergy Induced by Specific Immunotherapy. 2008; Int Arch Allergy Immunol, 147:171–178
  100. Karamloo, F., Schmitz, N., Scheurer, S., Foetisch, K., Hoffmann, A., Haustein, D., and Vieths, S. (1999). Molecular cloning and characterization of a birch pollen minor allergen, Bet v 5, belonging to a family of isoflavone reductase-related proteins. J Allergy Clin Immunol 104, 991-999.
  101. Weiner, H. L., Friedman, A., Miller, A., Khoury, S. J., al-Sabbagh, A., Santos, L., Sayegh, M., Nussenblatt, R. B., Trentham, D. E., and Hafler, D. A. (1994). Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 12, 809- 837.
  102. Ishizaka, K., Ishizaka, T., and Hornbrook, M. M. (1966a). Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol 97, 75-85.
  103. Ishizaka, K., Ishizaka, T., and Hornbrook, M. M. (1966b). Physicochemical properties of reaginic antibody. V. Correlation of reaginic activity wth gamma-E-globulin antibody. J Immunol 97, 840-853.
  104. Majkowska-Wojciechowska, B., Pelka, J., Korzon, L., Kozlowska, A., Kaczala, M., Jarzebska, M., Gwardys, T., and Kowalski, M. L. (2007). Prevalence of allergy, patterns of allergic sensitization and allergy risk factors in rural and urban children. Allergy 62, 1044-1050.
  105. Wuthrich, B., Schindler, C., Leuenberger, P., and Ackermann-Liebrich, U. (1995). Prevalence of atopy and pollinosis in the adult population of Switzerland (SAPALDIA study). Swiss Study on Air Pollution and Lung Diseases in Adults. Int Arch Allergy Immunol 106, 149- 156.
  106. Pajno, G. B., Barberio, G., De Luca, F., Morabito, L., and Parmiani, S. (2001). Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy 31, 1392-1397.
  107. Zhu, Z., Homer, R. J., Wang, Z., Chen, Q., Geba, G. P., Wang, J., Zhang, Y., and Elias, J. A. (1999). Pulmonary expression of interleukin-13 causes inflammation, mucus Originalarbeiten Christian Möbs, Caroline Slotosch, Harald Löffler, Thilo Jakob, Michael Hertl, and Wolfgang Pfützner Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation. 2010; J Immunol, 184:2194-2203
  108. Valenta, R., and Niederberger, V. (2007). Recombinant allergens for immunotherapy. J Allergy Clin Immunol 119, 826-830.
  109. Renzi, P. M., Turgeon, J. P., Marcotte, J. E., Drblik, S. P., Berube, D., Gagnon, M. F., and Spier, S. (1999). Reduced interferon-gamma production in infants with bronchiolitis and asthma.
  110. Schmidt-Weber, C. B., and Blaser, K. (2004). Regulation and role of transforming growth factor- beta in immune tolerance induction and inflammation. Curr Opin Immunol 16, 709-716.
  111. Kawano, Y., Noma, T., and Yata, J. (1994). Regulation of human IgG subclass production by cytokines. IFN-gamma and IL-6 act antagonistically in the induction of human IgG1 but additively in the induction of IgG2. J Immunol 153, 4948-4958.
  112. Szabo, S. J., Dighe, A. S., Gubler, U., and Murphy, K. M. (1997). Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185, 817-824.
  113. Romagnani, S. (2006). Regulation of the T cell response. Clin Exp Allergy 36, 1357-1366.
  114. Torgerson, T. R. (2006). Regulatory T cells in human autoimmune diseases. Springer Semin Immunopathol 28, 63-76.
  115. Ling, E. M., Smith, T., Nguyen, X. D., Pridgeon, C., Dallman, M., Arbery, J., Carr, V. A., and Robinson, D. S. (2004). Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363, 608-615.
  116. Venkataraman, C., Leung, S., Salvekar, A., Mano, H., and Schindler, U. (1999). Repression of IL-4-induced gene expression by IFN-gamma requires Stat1 activation. J Immunol 162, 4053-4061.
  117. Sutterwala, F. S., Noel, G. J., Salgame, P., and Mosser, D. M. (1998). Reversal of proinflammatory responses by ligating the macrophage Fcgamma receptor type I. J Exp Med 188, 217-222.
  118. Platts-Mills, T., Vaughan, J., Squillace, S., Woodfolk, J., and Sporik, R. (2001). Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population- based cross-sectional study. Lancet 357, 752-756.
  119. Signal transducer and activator of transcription 4 is required for the transcription factor T- bet to promote T helper 1 cell-fate determination. Immunity 29, 679-690.
  120. von Mutius, E., Martinez, F. D., Fritzsch, C., Nicolai, T., Reitmeir, P., and Thiemann, H. H. (1994). Skin test reactivity and number of siblings. Bmj 308, 692-695.
  121. Auflage). Spektrum Akademischer Verlag GmbH.
  122. Kaplan, M. H., Schindler, U., Smiley, S. T., and Grusby, M. J. (1996). Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4, 313-319.
  123. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., and Sakaguchi, S. (2002). Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3, 135-142.
  124. Usui, T., Preiss, J. C., Kanno, Y., Yao, Z. J., Bream, J. H., O'Shea, J. J., and Strober, W. (2006). T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203, 755-766.
  125. Schwartz, R. H. (2003). T cell anergy. Annu Rev Immunol 21, 305-334.
  126. Woodfolk, J. A. (2007). T-cell responses to allergens. J Allergy Clin Immunol 119, 280-294; quiz 295-286.
  127. Marie, J. C., Letterio, J. J., Gavin, M., and Rudensky, A. Y. (2005). TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 201, 1061-1067.
  128. Oboki, K., Ohno, T., Saito, H., and Nakae, S. (2008). Th17 and allergy. Allergol Int 57, 121-134.
  129. Soroosh, P., and Doherty, T. A. (2009). Th9 and allergic disease. Immunology 127, 450-458.
  130. Plewako, H., Arvidsson, M., Petruson, K., Oancea, I., Holmberg, K., Adelroth, E., Gustafsson, H., Sandstrom, T., and Rak, S. (2002). The effect of omalizumab on nasal allergic inflammation. J Allergy Clin Immunol 110, 68-71.
  131. Keskin, O., Tuncer, A., Adalioglu, G., Sekerel, B. E., Sackesen, C., and Kalayci, O. (2006). The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis. Pediatr Allergy Immunol 17, 396-407.
  132. Wills-Karp, M., Santeliz, J., and Karp, C. L. (2001). The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 1, 69-75.
  133. Shevach, E. M., and Stephens, G. L. (2006). The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity? Nat Rev Immunol 6, 613-618.
  134. M. (2006). The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev 212, 60-73.
  135. Jarnicki, A. G., and Fallon, P. G. (2003). T helper type-2 cytokine responses: potential therapeutic targets. Curr Opin Pharmacol 3, 449-455.
  136. Platts-Mills, T. A. (2001). The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med 164, S1-5.
  137. Zheng, W., and Flavell, R. A. (1997). The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89, 587-596.
  138. Satoguina, J. S., Adjobimey, T., Arndts, K., Hoch, J., Oldenburg, J., Layland, L. E., and Hoerauf, A. (2008). Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR/GITR-L interaction, IL-10 and TGF-beta. Eur J Immunol 38, 3101-3113.
  139. Satoguina, J. S., Weyand, E., Larbi, J., and Hoerauf, A. (2005). T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J Immunol 174, 4718-4726.
  140. Weber, R. W. (2003). White birch. Ann Allergy Asthma Immunol 91, A-6.
  141. Wilson, D. R., Irani, A. M., Walker, S. M., Jacobson, M. R., Mackay, I. S., Schwartz, L. B., and Durham, S. R. (2001). Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium. Clin Exp Allergy 31, 1705-1713.
  142. Thunberg, S., Akdis, M., Akdis, C. A., Gronneberg, R., Malmstrom, V., Trollmo, C., van Hage, M., and Gafvelin, G. (2007). Immune regulation by CD4+CD25+ T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls. Clin Exp Allergy 37, 1127-1136.
  143. Jutel, M., Akdis, M., Blaser, K., and Akdis, C. A. (2006). Mechanisms of allergen specific immunotherapy--T-cell tolerance and more. Allergy 61, 796-807.
  144. Valovirta, E., Jacobsen, L., Ljorring, C., Koivikko, A., and Savolainen, J. (2006). Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children. Allergy 61, 1177-1183.
  145. Traidl-Hoffmann, C., Mariani, V., Hochrein, H., Karg, K., Wagner, H., Ring, J., Mueller, M. J., Jakob, T., and Behrendt, H. (2005). Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J Exp Med 201, 627-636.
  146. Polosa, R., Al-Delaimy, W. K., Russo, C., Piccillo, G., and Sarva, M. (2005). Greater risk of incident asthma cases in adults with allergic rhinitis and effect of allergen immunotherapy: a retrospective cohort study. Respir Res 6, 153.
  147. Platts-Mills, T. A., and Cooper, P. J. (2010). Differences in asthma between rural and urban communities in South Africa and other developing countries. J Allergy Clin Immunol 125, 106-107.
  148. Williams, A. P., Krishna, M. T., and Frew, A. J. (2004). The safety of immunotherapy. Clin Exp Allergy 34, 513-514.
  149. Woodcock, A., Lowe, L. A., Murray, C. S., Simpson, B. M., Pipis, S. D., Kissen, P., Simpson, A., and Custovic, A. (2004). Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years. Am J Respir Crit Care Med 170, 433-439.
  150. Sokol, C. L., Barton, G. M., Farr, A. G., and Medzhitov, R. (2008). A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 9, 310-318.
  151. Johansson, S. G., and Bennich, H. (1967). Immunological studies of an atypical (myeloma) immunoglobulin. Immunology 13, 381-394.
  152. van der Zee, J. S., van Swieten, P., and Aalberse, R. C. (1986). Inhibition of complement activation by IgG4 antibodies. Clin Exp Immunol 64, 415-422.
  153. Family history and the risk of early-onset persistent, early-onset transient, and late-onset asthma. Epidemiology 12, 577-583.
  154. Till, S., Walker, S., Dickason, R., Huston, D., O'Brien, F., Lamb, J., Kay, A. B., Corrigan, C., and Durham, S. (1997). IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis. Clin Exp Immunol 110, 114-121.
  155. Secrist, H., Chelen, C. J., Wen, Y., Marshall, J. D., and Umetsu, D. T. (1993). Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med 178, 2123-2130.
  156. Palframan, R. T., Collins, P. D., Severs, N. J., Rothery, S., Williams, T. J., and Rankin, S. M. (1998). Mechanisms of acute eosinophil mobilization from the bone marrow stimulated by interleukin 5: the role of specific adhesion molecules and phosphatidylinositol 3-kinase. J Exp Med 188, 1621-1632.
  157. Karlsson, M. R., Rugtveit, J., and Brandtzaeg, P. (2004). Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy. J Exp Med 199, 1679-1688.
  158. Schuurman, J., Van Ree, R., Perdok, G. J., Van Doorn, H. R., Tan, K. Y., and Aalberse, R. C. (1999). Normal human immunoglobulin G4 is bispecific: it has two different antigen- combining sites. Immunology 97, 693-698.
  159. Olsson, T., Zhi, W. W., Hojeberg, B., Kostulas, V., Jiang, Y. P., Anderson, G., Ekre, H. P., and Link, H. (1990). Autoreactive T lymphocytes in multiple sclerosis determined by antigen- induced secretion of interferon-gamma. J Clin Invest 86, 981-985.
  160. Punnonen, J., Aversa, G., Cocks, B. G., McKenzie, A. N., Menon, S., Zurawski, G., de Waal Malefyt, R., and de Vries, J. E. (1993). Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A 90, 3730-3734.
  161. Teixeira, L. K., Fonseca, B. P., Barboza, B. A., and Viola, J. P. (2005). The role of interferon- gamma on immune and allergic responses. Mem Inst Oswaldo Cruz 100 Suppl 1, 137- 144.
  162. Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., and Glimcher, L. H. (2000). A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669.
  163. Senti, G., Prinz Vavricka, B. M., Erdmann, I., Diaz, M. I., Markus, R., McCormack, S. J., Simard, J. J., Wuthrich, B., Crameri, R., Graf, N., et al. (2008). Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A 105, 17908-17912.
  164. Nouri-Aria, K. T., Wachholz, P. A., Francis, J. N., Jacobson, M. R., Walker, S. M., Wilcock, L. K., Staple, S. Q., Aalberse, R. C., Till, S. J., and Durham, S. R. (2004). Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172, 3252-3259.
  165. Wachholz, P. A., Soni, N. K., Till, S. J., and Durham, S. R. (2003). Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 112, 915-922.

* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten
© UB Marburg 1997 - 2024 Universitätsbibliothek Marburg