Die Regulation der Immunantwort bei der allergischen Rhinitis durch T-Lymphozyten

Zusammenfassung

Allergische Beschwerden äußern sich in einer Vielzahl von Symptomen, welche in direkter Abhängigkeit vom Allergen selbst und dem Ort, an dem sie mit dem Körper interagieren, stehen. So führt der Kontakt des Allergens mit den oberen Atemwegen zu Konjunktivitis oder allergischer Rhinitis. Neben den antigenpräsentierenden Zellen wird den T-Lymphozyten eine zentrale Rolle in dieser Hypersensibilitätsreaktion zuteil. Durch die Produktion und Sekretion von Zytokinen erfolgt die Ausbildung sowie die Aufrechterhaltung der entsprechenden Th-Immunantwort. Neben regulierenden Funktionen haben T-Zellen bei allergischen Entzündungsreaktionen der Nasenschleimhaut ebenfalls Einfluss auf einen möglichen chronischen Verlauf der Erkrankung und stellen interessante Zielzellen für die spezifische Immuntherapie sowie die Glukokortikoid-Therapie dar. Der vorliegende Artikel beleuchtet die spezifischen Funktionen von T-Zellen während der allergischen Rhinitis und zeigt die Grundlagen für das Verständnis der Wirkweise immunmodulatorischer Therapien und der Chronifizierung entzündlicher Nasenschleimhauterkrankungen auf.

Abstract

Allergic diseases show a broad variety of symptoms, depending on the type of allergen and the location where it interacts with the human body. Contact of allergens with the upper respiratory tract result in conjunctivitis or allergic rhinitis. Apart from antigenpresenting cells, T-cells do play an important role in this hypersensibility reaction. Due to the production and secretion of cytokines, T-lymphocytes induce and maintain the corresponding Th-immuneresponse. In addition to regulatory functions, T-cells have potential influence on the chronic progression of allergic inflammatory reactions of the nasal mucosa and are therefore interesting target cells for specific immunotherapy as well as corticosteroid treatment. This article shows the specific function of T-cells during allergic rhinitis and reveals the basics for understanding the mechanism of immunotherapy and chronification of inflammatory allergic diseases of the nasal mucosa.

Schlüsselwörter

Allergie - Rhinitis - T-Lymphozyten - Nasenschleimhaut - spezifische Immuntherapie - Glukokortikoid

Key words

allergy - allergic rhinitis - T-lymphocytes - nasal mucosa - corticosteroid - specific immunotherapy

Literatur

• 1 Baker C, Altman L C. The effect of dexamethasone and cromolyn sodium on intrercellular adhesion molecules-1 expression on human nasal epithelial cells.  J Allergy Clin Immunol. 1992;  89 212
• 2 Baroody F M, Rouadi P, Driscoll P V. et al . Intranasal beclomethasone reduces allergen-induced symptoms and superficial mucosal eosinophilia without affecting submucosal inflammation.  Am J Respir Crit Care Med. 1998;  157 899-906
• 3 Bascom R, Wachs M, Naclerio R M. et al . Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment.  J Allergy Clin Immunol. 1988;  81 580-589
• 4 Belladonna M L, Renauld J C, Bianchi R. et al . IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells.  J Immunol. 2002;  168 5448-5454
• 5 Bellinghausen I, Brand P, Bottcher I. et al . Production of interleukin-13 by human dendritic cells after stimulation with protein allergens is a key factor for induction of T helper 2 cytokines and is associated with activation of signal transducer and activator of transcription-6.  Immunology. 2003;  108 167-176
• 6 Bentley A M, Cumberworth V, Varney V A. Studies during the pollen season in understanding allergic rhinitis.  In: Godard P, Bousquet J, Michel FB (Hrsg). Advances in allergology and clinical immunology.  Carnforth; Munksgaard/Kopenhagen 1992: 457-464
• 7 Bottcher I, Bellinghausen I, Konig B. et al . Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus contact allergens.  Immunology. 2008;  123 139-144
• 8 Calderon M A, Lozewicz S, Prior A. et al . Lymphocyte infiltration and thickness of the nasal mucous membrane in perennial and seasonal allergic rhinitis.  J Allergy Clin Immunol. 1994;  93 635-643
• 9 Cox G, Ohtoshi T, Vancheri C. et al . Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids.  Am J Respir Cell Mol Biol. 1991;  4 525-531
• 10 Daser A, Herz U, Werfel T. et al . Mechanismen der T-Zell-Aktivierung in der allergologischen Entzündung.  Allergologie. 1996;  19 166-170
• 11 de Jong E C, Smits H H, Kapsenberg M L. Dendritic cell-mediated T cell polarization.  Springer Semin Immunopathol. 2005;  26 289-307
• 12 Dormann D, Montermann E, Klimek L. et al . Heterogeneity in the polyclonal T cell response to birch pollen allergens.  Int Arch Allergy Immunol. 1997;  114 272-277
• 13 Egwuagu C E, Yu C R, Zhang M. et al . Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance.  J Immunol. 2002;  168 3181-3187
• 14 Frucht D M, Fukao T, Bogdan C. et al . IFN-gamma production by antigen-presenting cells: mechanisms emerge.  Trends Immunol. 2001;  22 556-560
• 15 Grabbe S, Schwarz T. Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity.  Immunol Today. 1998;  19 37-44
• 16 Grewe M, Bruijnzeel-Koomen C A, Schopf E. et al . A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis.  Immunol Today. 1998;  19 359-361
• 17 Hamid Q, Boguniewicz M, Leung D Y. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis.  J Clin Invest. 1994;  94 870-876
• 18 Igarashi Y, Goldrich M S, Kaliner M A. et al . Quantitation of inflammatory cells in the nasal mucosa of patients with allergic rhinitis and normal subjects.  J Allergy Clin Immunol. 1995;  95 716-725
• 19 Kadowaki N, Ho S, Antonenko S. et al . Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.  J Exp Med. 2001;  194 863-869
• 20 Kalinski P, Moser M. Consensual immunity: success-driven development of T-helper-1 and T-helper-2 responses.  Nat Rev Immunol. 2005;  5 251-260
• 21 Kapsenberg M L, Kalinski P. The concept of type 1 and type 2 antigen-presenting cells.  Immunol Lett. 1999;  69 5-6
• 22 Kay A B. Asthma and inflammation.  J Allergy Clin Immunol. 1991;  87 893-910
• 23 Klimek L. Die immunregulative Wirkung zellulärer Rezeptormoleküle am Beispiel des HLA-II-Rezeptors in der Nahrungsmittelallergie.  Allergologie. 1992;  15 176-179
• 24 Klimek L. Einfluss der Immuntherapie auf Symptomatik, Zellaktivierungsmarker und inflammatorische Mediatoren bei allergischer Rhinitis.  Allergo J. 1997;  6 158-160
• 25 Klimek L, Kahl L, Bene M C. et al . Spezifische Plasmazellpopulationen in humanen Gaumentonsillen nach oraler Immunstimulation.  Allergologie. 1993;  16 194-197
• 26 Klimek L, Reske-Kunz A B, Saloga J. Spezifische Hyposensibilisierungstherapie.  Stuttgart; Thieme 1997
• 27 Klimek L, Riechelmann H, Saloga J. et al .Allergologie und Umweltmedizin.  Stuttgart, New York; Schattauer 1997
• 28 Klimek L, Saloga J, Knop J. et al .Die allergische Rhinitis.  Stuttgart, New York; Schattauer 1997
• 29 Kurata H, Lee H J, O’Garra A. et al . Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells.  Immunity. 1999;  11 677-688
• 30 Lugo-Villarino G, Maldonado-Lopez R, Possemato R. et al . T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells.  Proc Natl Acad Sci USA. 2003;  100 7749-7754
• 31 Mattoli S, Vittori E, Marini M. Corticosteroids downregulate the increased expression of GM-CSF, IL-6 and IL-8 in bronchial epithelium of asthmatic patients.  J Allergy Clin Immunol. 1992;  89 164
• 32 Moser M, Murphy K M. Dendritic cell regulation of TH1-TH2 development.  Nat Immunol. 2000;  1 199-205
• 33 Mosmann T R, Li L, Sad S. Functions of CD8 T-cell subsets secreting different cytokine patterns.  Semin Immunol. 1997;  9 87-92
• 34 Mygind N, Lund V. Topical corticosteroid therapy of rhinitis.  Clin Immunother. 1996;  5 353-358
• 35 Naclerio R M. Inflammation in allergic rhinitis.  Res Clin Forums. 1992;  14 49-55
• 36 Okuda M, Otsuka H. Basophilic cells in allergic nasal secretions.  Arch Otorhinolaryngol. 1977;  214 283-289
• 37 Okuda M, Otsuka H, Sakaguchi K. et al . Effect of anti-allergic treatment on nasal surface basophilic metachromatic cells in allergic rhinitis.  Allergy Proc. 1989;  10 23-26
• 38 Ouyang W, Ranganath S H, Weindel K. et al . Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.  Immunity. 1998;  9 745-755
• 39 Parham C, Chirica M, Timans J. et al . A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.  J Immunol. 2002;  168 5699-5708
• 40 Powe D G, Huskisson R S, Carney A S. et al . Mucosal T-cell phenotypes in persistent atopic and nonatopic rhinitis show an association with mast cells.  Allergy. 2004;  59 204-212
• 41 Pulendran B, Lingappa J, Kennedy M K. et al . Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.  J Immunol. 1997;  159 2222-2231
• 42 Rak S, Jacobson M R, Sudderick R M. et al . Influence of prolonged treatment with topical corticosteroid (fluticasone propionate) on early and late phase nasal responses and cellular infiltration in the nasal mucosa after allergen challenge.  Clin Exp Allergy. 1994;  24 930-939
• 43 Rissoan M C, Soumelis V, Kadowaki N. et al . Reciprocal control of T helper cell and dendritic cell differentiation.  Science. 1999;  283 1183-1186
• 44 Rosenwasser L J. Genetics of asthma and atopy.  Toxicol Lett. 1996;  86 73-77
• 45 Saloga J, Klimek L, Bellinghausen I. et al . Assessment of clinical and immunological changes following specific allergen immunotherapy in patients with allergic rhinitis to birch pollen.  Allergo J. 1996;  5 331-338
• 46 Shimoda K, van Ebster D J, Sangster M Y. et al . Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene.  Nature. 1996;  380 630-633
• 47 Tas S W, de Jong E C, Hajji N. et al . Selective inhibition of NF-kappaB in dendritic cells by the NEMO-binding domain peptide blocks maturation and prevents T cell proliferation and polarization.  Eur J Immunol. 2005;  35 1164-1174
• 48 Thepen T, Langeveld-Wildschut E G, Bihari I C. et al . Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study.  J Allergy Clin Immunol. 1996;  97 828-837
• 49 van de Steen S A, Caldenhoven E, Raaijmakers J A. et al . Glucocorticoid-mediated repression of intercellular adhesion molecule-1 expression in human monocytic and bronchial epithelial cell lines.  Am J Respir Cell Mol Biol. 1993;  8 340-347
• 50 Weido A J, Reece L M, Alam R. et al . Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis.  Ann Allergy Asthma Immunol. 1996;  77 407-415
• 51 Werfel T, Ahlers G, Reekers R. et al .Ekzemreaktionen auf Nahrungsmittelallergene bei atopischer Dermatitis: Klinische und immunologische Befunde.  In: Wüthrich B (Hrsg). Nahrungsmittelallergien.  München; Dustri Verlag 1996: 186-196
• 52 Werfel T, Kapp A. Zytokine als Mediatoren allergischer Organreaktionen.  Allergologie. 1997;  20 546-550
• 53 Werfel T, Kapp A. Immunologische Befunde bei atopischer Dermatitis.  Allergologie. 1998;  21 251-258
• 54 Werfel T, Morita A, Grewe M. et al . Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis.  J Invest Dermatol. 1996;  107 871-876
• 55 Zheng W, Flavell R A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.  Cell. 1997;  89 587-596