Original Articles: Mechanisms of Allergy
Late asthmatic reactions provoked by intradermal injection of T-cell peptide epitopes are not associated with bronchial mucosal infiltration of eosinophils or TH2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid,☆☆

https://doi.org/10.1067/mai.2001.117460Get rights and content

Abstract

Background: Isolated late asthmatic reactions can be provoked by intradermal challenge of allergen-derived T-cell peptide epitopes. Objective: The purpose of this study was to determine whether the isolated LAR is associated with the local accumulation of inflammatory cells, the expression of TH2 cytokines, and the production of pharmacologic mediators. Methods: A randomized, placebo-controlled, crossover study design was used. The investigation involved bronchial and skin biopsies and bronchoalveolar lavage (BAL) fluids from 8 cat-allergic subjects who developed significant late asthmatic reactions 6 hours after intradermal injection of Fel d 1 chain 1–derived peptides (FC1Ps). Results: Immunostaining of bronchial biopsy specimens showed no changes in the numbers of eosinophils, neutrophils, basophils, mast cells, CD3+, CD4+ or CD8+ T cells, CD25+ cells or macrophages, or cells mRNA+ for IL-4, IL-5, or IL-13 when the FC1P day was compared with the diluent control day. There were also no significant differences in eosinophil numbers, either in BAL fluids or in peripheral blood after FC1P challenge. Furthermore, there were no significant alterations in the concentrations of histamine, histamine-releasing factors, or eicosanoids (LTC4/D4/E4, PGD2, PGE2, TXB2, PGF) in BAL fluids. FC1Ps induced a significant (P < .05) elevation in CD8+ cells in the skin and an unexpected decrease in IL-5 in BAL fluids (P = .043). Conclusion: Part of the asthma process might involve T cell–dependent airway narrowing with no requirement for IgE, mast cells, or infiltrating inflammatory cells. (J Allergy Clin Immunol 2001;108:394-401.)

Section snippets

Study design

All subjects were documented cat-allergic asthmatic individuals, as defined previously.1 Thirty-four people entered the study. At each initial assessment, the study was explained in detail and the patient completed an asthma and allergy questionnaire that recorded sensitivity to allergens, asthma symptoms, and general health and medication information. Each of the 34 patients was given a physical examination, and allergic status was assessed by skin prick tests to a panel of common

Cutaneous and asthmatic reactions to intradermal Fel d 1 chain 1 peptides

Six of the 8 patients studied had no visible local cutaneous reaction to the FC1P. Each of 2 subjects developed a wheal that was slightly larger than that observed with diluent alone at 15 minutes (though smaller than that observed with whole allergen). One subject had a visible late cutaneous reaction to intradermal injection of FC1P at 6 hours. None of the 26 FC1P nonresponders had late cutaneous reactions to the peptides. All 34 subjects developed immediate and late-phase cutaneous reactions

Discussion

We recently described IgE-independent isolated LARs elicited by intradermal adminstration of allergen-derived T-cell peptide epitopes. The evidence that linear, allergen-derived, peptide-induced LARs are T cell–dependent includes the following. First, as described previously,1 the FC1P peptides induced T-cell proliferation but not histamine release from peripheral blood basophils. Second, responsiveness of subjects with asthma, in terms of the development of LAR, appears to be MHC class

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    Funded by the National Asthma Campaign (UK), and by GM 15431 from the National Institutes of Health.

    ☆☆

    Reprint requests: A.B. Kay, Professor and Head, Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, United Kingdom.

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