High-dose Allergen Exposure Leads to Tolerance

Overview

Journal Clin Rev Allergy Immunol

Specialty Allergy & Immunology

Date 2005 Apr 19

PMID 15834168

Citations 3

Authors

Judith A Woodfolk

Affiliations

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Abstract

Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, high-titer IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.

Citing Articles

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References

Akbari O, DeKruyff R, Umetsu D . Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol. 2001; 2(8):725-31. DOI: 10.1038/90667. View

Lindfors A, Wickman M, Hedlin G, Pershagen G, Rietz H, Nordvall S . Indoor environmental risk factors in young asthmatics: a case-control study. Arch Dis Child. 1995; 73(5):408-12. PMC: 1511369. DOI: 10.1136/adc.73.5.408. View

Luczynska C, Li Y, Chapman M, Platts-Mills T . Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I. Am Rev Respir Dis. 1990; 141(2):361-7. DOI: 10.1164/ajrccm/141.2.361. View

Van Neerven R, Wikborg T, Lund G, Jacobsen B, Arnved J, Ipsen H . Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol. 1999; 163(5):2944-52. View

Bolte G, BISCHOF W, Borte M, Lehmann I, Wichmann H, Heinrich J . Early endotoxin exposure and atopy development in infants: results of a birth cohort study. Clin Exp Allergy. 2003; 33(6):770-6. DOI: 10.1046/j.1365-2222.2003.01665.x. View

Reefer A, Carneiro R, Custis N, Platts-Mills T, Sung S, Hammer J . A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. J Immunol. 2004; 172(5):2763-72. DOI: 10.4049/jimmunol.172.5.2763. View

Ewbank P, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson H . A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract. J Allergy Clin Immunol. 2003; 111(1):155-61. DOI: 10.1067/mai.2003.41. View

Chen W, Jin W, Hardegen N, Lei K, Li L, Marinos N . Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003; 198(12):1875-86. PMC: 2194145. DOI: 10.1084/jem.20030152. View

de Blay F, Heymann P, Chapman M, Platts-Mills T . Airborne dust mite allergens: comparison of group II allergens with group I mite allergen and cat-allergen Fel d I. J Allergy Clin Immunol. 1991; 88(6):919-26. DOI: 10.1016/0091-6749(91)90249-n. View

10.

Eisenbarth S, Piggott D, Huleatt J, Visintin I, Herrick C, Bottomly K . Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med. 2002; 196(12):1645-51. PMC: 2196061. DOI: 10.1084/jem.20021340. View

11.

Svanes C, Jarvis D, Chinn S, Burney P . Childhood environment and adult atopy: results from the European Community Respiratory Health Survey. J Allergy Clin Immunol. 1999; 103(3 Pt 1):415-20. DOI: 10.1016/s0091-6749(99)70465-3. View

12.

Custovic A, Simpson A, Pahdi H, Green R, Chapman M, Woodcock A . Distribution, aerodynamic characteristics, and removal of the major cat allergen Fel d 1 in British homes. Thorax. 1998; 53(1):33-8. PMC: 1758692. DOI: 10.1136/thx.53.1.33. View

13.

Linneberg A, Nielsen N, Madsen F, Frolund L, Dirksen A, Jorgensen T . Pets in the home and the development of pet allergy in adulthood. The Copenhagen Allergy Study. Allergy. 2003; 58(1):21-6. DOI: 10.1034/j.1398-9995.2003.23639.x. View

14.

Akdis C, Blaser K . IL-10-induced anergy in peripheral T cell and reactivation by microenvironmental cytokines: two key steps in specific immunotherapy. FASEB J. 1999; 13(6):603-9. DOI: 10.1096/fasebj.13.6.603. View

15.

Cottrez F, Hurst S, Coffman R, Groux H . T regulatory cells 1 inhibit a Th2-specific response in vivo. J Immunol. 2000; 165(9):4848-53. DOI: 10.4049/jimmunol.165.9.4848. View

16.

Almqvist C, Egmar A, Hedlin G, Lundqvist M, Nordvall S, Pershagen G . Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort. Clin Exp Allergy. 2003; 33(9):1190-7. DOI: 10.1046/j.1365-2222.2003.01764.x. View

17.

Djurup R, Osterballe O . IgG subclass antibody response in grass pollen-allergic patients undergoing specific immunotherapy. Prognostic value of serum IgG subclass antibody levels early in immunotherapy. Allergy. 1984; 39(6):433-41. DOI: 10.1111/j.1398-9995.1984.tb01965.x. View

18.

Akdis C, Blesken T, Akdis M, Wuthrich B, Blaser K . Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998; 102(1):98-106. PMC: 509070. DOI: 10.1172/JCI2250. View

19.

Hesselmar B, ABERG B, Eriksson B, Bjorksten B, Aberg N . High-dose exposure to cat is associated with clinical tolerance--a modified Th2 immune response?. Clin Exp Allergy. 2003; 33(12):1681-5. DOI: 10.1111/j.1365-2222.2003.01821.x. View

20.

ROOST H, Kunzli N, Schindler C, Jarvis D, Chinn S, Perruchoud A . Role of current and childhood exposure to cat and atopic sensitization. European Community Respiratory Health Survey. J Allergy Clin Immunol. 1999; 104(5):941-7. DOI: 10.1016/s0091-6749(99)70072-2. View