Hypersensitivity reactions after respiratory sensitization: Effect of intranasal peptides containing T-cell epitopes

doi:10.1067/mai.2002.128485

Journal of Allergy and Clinical Immunology

Volume 110, Issue 4, October 2002, Pages 610-616

https://doi.org/10.1067/mai.2002.128485 Get rights and content

Abstract

Background: The intranasal administration of peptides containing T-cell epitopes has been shown to inhibit T-cell and antibody responses of mice injected with allergen, but responses to respiratory sensitization might be regulated differently. Objective: This study was designed to examine the effect of intranasal peptide on antigen-induced lung inflammatory responses and delayed hypersensitivity after sensitization by the respiratory mucosa or without sensitization. Methods: Mice were treated with an intranasal tolerizing regimen of a peptide containing the major T-cell epitope of Der p 1. Delayed hypersensitivity and lung inflammation to challenge with Der p 1 was measured either without further treatment or after sensitization induced by means of the intranasal administration of Der p 1 with a mutated enterotoxin adjuvant. Lung inflammatory responses were examined by means of lavage and histologic section, and delayed hypersensitivity responses were measured on the basis of ear swelling. Results: Delayed hypersensitivity reactions were induced in mice treated with intranasal peptide, and large reactions were found in mice given intranasal peptide and sensitized with intranasal Der p 1 and adjuvant. Mice pretreated with peptide and sensitized with Der p 1 had an increased lymphocytic infiltration after allergen-specific challenge, as measured by means of bronchoalveolar lavage and shown histologically. These hypersensitivity results are in contrast to previous data that show tolerance to injected antigen. Conclusions: Although the intranasal administration of a peptide containing a T-cell epitope markedly inhibits responses to sensitization produced by the injection of allergen, the peptide induces immune responses and increases hypersensitivity to respiratory sensitization. (J Allergy Clin Immunol 2002;110:610-6.)

Section snippets

Mice

Specific pathogen-free C57BL/6 mice (6-8 weeks old) were obtained from the Animal Resource Centre (Murdoch, Australia).

Antigens and peptides

Der p 1 was isolated from a 20% solution of spent mite media (a gift from CSL-Ltd, Melbourne, Australia) dissolved in PBS by means of affinity chromatography with mAb 4C1 provided by Dr M. D. Chapman (Indoor Biotechnologies, Charlottesville, Va). Human serum albumin (HSA) was purchased from Sigma (St Louis, Mo). The peptide representing residues 114-128 of Der p 1.0101¹⁹

Results

Mice were given 5 daily doses of the Der p 1 peptide to examine the effect of intranasal peptide treatment on respiratory sensitization, and after 10 days, they were sensitized by means of an intranasal administration of Der p 1 in mutant toxin. After a further 4 weeks, the mice were challenged with intranasal administration of 100 μg of Der p 1 on 3 consecutive days, and bronchoalveolar lavage fluid and lung histologic specimens were examined the next day. The inflammation was compared with

Discussion

The intranasal administration of Der p 1 peptide has been shown to profoundly inhibit IgE antibody responses of mice injected with Der p 1 in alum¹² and to inhibit delayed hypersensitivity and IL-2, IFN-γ, and IL-5 responses of mice immunized with the allergen in CFA.11, 12 This concurs with studies of others with intranasal administration of allergen1, 2, 3, 4, 5 or peptides.13, 14, 15 In contrast, when the sensitization was performed intranasally, neither the IgE and IgG antibody responses

References (37)

DC Tsitoura et al.
Mechanisms preventing allergen-induced airways hyperreactivity: role of tolerance and immune deviation
J Allergy Clin Immunol
(2000)
W Smith et al.
Allergens of wild house dust mites: environmental Der p 1 and Der p 2 sequence polymorphisms
J Allergy Clin Immunol
(2001)
N Kamiya et al.
Long-term persistence of cellular immunity to Oka vaccine virus induced by pernasal co-administration with Escherichia coli enterotoxin in mice
Vaccine
(2001)
MJ Pallen et al.
An abundance of bacterial ADP-ribosyltransferases -implications for the origin of exotoxins and their human homologues
Trends Microbiol
(2001)
MP Davenport et al.
A homing selection hypothesis for T-cell trafficking
Immunol Today
(2000)
PG Holt et al.
Inhibition of specific IgE responses by pre-exposure to inhaled antigen
Immunology
(1981)
AG van Halteren et al.
Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosa tolerance induction
J Immunol
(1997)
DA Wolvers et al.
Mucosal tolerance is associated with but independent of, up-regulation Th2 responses
Immunology
(1997)
U Wiedermann et al.
Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type 1 allergy
J Allergy Clin Immunol
(1999)
U Wiedermann et al.
Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type 1 allergy
Int Immunol
(1999)

C McMenamin et al.

The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production

J Exp Med

(1993)

B Metzler et al.

Inhibition of experimental autoimmune encephalomyelitis by inhalation but not oral administration of the encephalitogenic peptide: influence of MHC binding affinity

Int Immunol

(1993)

GF Hoyne et al.

Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice

J Exp Med

(1993)

GF Hoyne et al.

Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo

Int Immunol

(1996)

GF Hoyne et al.

Characterization of the specificity and duration of T cell tolerance to intranasally administered peptides in mice: a role intramolecular suppression

Int Immunol

(1997)

AG Jarnicki et al.

Inhibition of mucosal and systemic Th2-type immune responses by intranasal peptides containing a dominant T cell epitope of the allergen Der p 1

Int Immunol

(2001)

M Astori et al.

Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice

J Immunol

(2000)

EM Janssen et al.

The efficacy 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

(2000)

Cited by (3)

Downregulation of IgE antibody and allergic responses in the lung by epidermal biolistic microparticle delivery
2006, Journal of Allergy and Clinical Immunology
Citation Excerpt :
This is clearly different to the gene-gun DNA vaccination of Ludwig-Portugall et al,13 which induced TH1 immunity. It has been shown that a tolerizing procedure that inadvertently induced delayed hypersensitivity severely exacerbated lung inflammatory responses to allergen, and therefore downregulation instead of vaccination can be an advantage.34 The biolistic injections also markedly affected the lung response induced when the sensitized and boosted mice were challenged with aerosols of OVA.
Biolistic injections provide a needle-free delivery of antigen-laden microparticles to the epithelium. The precision of the injection preferentially targets the Langerhans cell network, which, although ideal for vaccination, might not be suitable for the downregulation of immune responses in immunotherapy.
We sought to determine the ability of biolistic injection of antigen into the epithelium of sensitized mice to inhibit IgE antibody and lung inflammatory responses produced by further exposure to antigen.
Mice were sensitized by means of a needle injection of ovalbumin (OVA) in alum and given a series of biolistic injections of OVA or vehicle control, followed by a boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after the boost. The mice were then challenged intranasally, and the infiltration of inflammatory cells was measured by means of bronchoalveolar lavage. Airway reactivity of the challenged mice was measured by examining responses to methacholine with forced oscillatory techniques.
Biolistic injection of OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1 antibody responses induced by boosting. IgG2a antibody responses were reduced rather than stimulated. The eosinophilic inflammation in the bronchoalveolar lavage fluid induced by intranasal challenge was also markedly inhibited. Lung hyperreactivity showed an initial increase and then a decrease of responsiveness to methacholine, with elastance returning to the level of unsensitized mice. Biolistic injection into the buccal epithelium was also inhibitory.
Biolistic injection of allergen inhibited the boosting of IgE antibody and eosinophilic lung inflammatory responses without inducing T_H1 immunity.
Animal models of type I allergy using recombinant allergens
2004, Methods
Various animal models including guinea pigs, monkeys, dogs, rats, and mice have been established in an attempt to provide insights into the complex immunological and pathophysiological mechanisms of human type I allergic diseases. The detailed knowledge of the murine genome, the various components of the murine immune system, and the generation of engineered mice has made the murine system the most attractive among all animal models. The availability of multitude technologies and reagents to characterize and manipulate immunological pathways and mediators adds to the outstanding opportunities to assess the pathology of allergic diseases and to develop novel therapeutic strategies in mice. Numerous sensitization protocols with food and aero-allergens are used to establish an allergic/asthma-like phenotype in mice. Requirements for an appropriate murine model include a close resemblance to the pathology of the disease in humans, the objective measurement of the physiologic parameters, as well as reliability and reproducibility of the experimental data. With respect to reproducible experimental conditions, it has been recognized that extract preparations from natural allergen sources can vary in their allergen-content and -composition. This might influence the degree of sensitization or the outcome of treatment strategies in dependence of the applied extract preparation. The use of recombinant allergens in experimental in vivo and in vitro systems can overcome these problems. Another aspect, that has become obvious from the experimental studies, is that allergens can differ in their immunogenicity as well as in their capacity to act as tolerogens. Therefore, it seems important that the efficacy of the different allergen-molecules to act as therapeutic agents is individually examined. In this review, examples of animal models are described, in which recombinant allergens have been used for sensitization and/or treatment of allergic responses and how they have been used to enhance our understanding of the pathology of allergic diseases.
Efficacy of local nasal immunotherapy for Dp2-induced airway inflammation in mice: Using Dp2 peptide and fungal immunomodulatory peptide
2003, Journal of Allergy and Clinical Immunology
Background: Local nasal immunotherapy (LNIT) is an effective immunotherapy. Peptides derived from the group 2 allergen of Dermatophagoides pteronyssinus , Dp2 28-40 and Dp2 28-40A, and fungal immunomodulatory peptide (FIP) have been shown to act as T_H1 potential and response-inducing adjuvant. LNIT by the use of Dp2 peptides in conjunction with FIP were investigated. Objective: We sought to determine whether Dp2-induced airway inflammation in mice could be downregulated by Dp2 peptides or a mixture of Dp2 peptides with FIP. Method: Mice were sensitized with rDp2 followed by LNIT with Dp2 peptides, FIP, or FIP and a mixture of Dp2 peptides. After intratracheal challenge with rDp2, the airway inflammation and hyperresponsiveness were determined by bronchoalveolar lavage fluid (BALF) analysis and methacholine challenge. Results: Both Dp2 peptides and FIP were able to inhibit rDp2-induced airway inflammation and airway hyperresponsiveness. An increase in IFN-γ and a decrease in IL-5 in BALF and sera were found after LNIT with Dp2 peptides, FIP, and mixtures of both. Serum levels of TGF-β were reduced after LNIT with FIP and Dp2 28-40. Penh values were significantly decreased after methacholine challenge in both the early and late phase. Conclusions: LNIT with allergen-derived peptides and FIP can produce an anti-inflammatory effect on allergen-induced airway inflammation. LNIT with selected peptides and FIP might be a good alternative therapy for allergic airway disease. (J Allergy Clin Immunol 2003;112:301-10.)

^☆: Supported by a grant from the Australian National Health and Medical Research Council.

^☆☆: Reprint requests: Wayne R. Thomas, PhD, TVW Telethon Institute for Child Health Research, PO Box 855, West Perth, Western Australia 6872, Australia.

View full text

Mechanisms of AllergyHypersensitivity reactions after respiratory sensitization: Effect of intranasal peptides containing T-cell epitopes☆,☆☆

Abstract

Section snippets

Mice

Antigens and peptides

Results

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

Vaccine

Trends Microbiol

Immunol Today

Inhibition of specific IgE responses by pre-exposure to inhaled antigen

Immunology

Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosa tolerance induction

J Immunol

Mucosal tolerance is associated with but independent of, up-regulation Th2 responses

Immunology

Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant bet v 1, the major birch pollen allergen, in a murine model of type 1 allergy

J Allergy Clin Immunol

Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type 1 allergy

Int Immunol

The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production

J Exp Med

Inhibition of experimental autoimmune encephalomyelitis by inhalation but not oral administration of the encephalitogenic peptide: influence of MHC binding affinity

Int Immunol

Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice

J Exp Med

Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo

Int Immunol

Characterization of the specificity and duration of T cell tolerance to intranasally administered peptides in mice: a role intramolecular suppression

Int Immunol

Inhibition of mucosal and systemic Th2-type immune responses by intranasal peptides containing a dominant T cell epitope of the allergen Der p 1

Int Immunol

Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice

J Immunol

The efficacy 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

Mechanisms of Allergy
Hypersensitivity reactions after respiratory sensitization: Effect of intranasal peptides containing T-cell epitopes☆,☆☆