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Published ahead of print on September 18, 2003, doi:10.1164/rccm.200305-690OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 1, January 2004, 20-26

A more recent version of this article appeared on January 1, 2004
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Submitted on June 2, 2003
Accepted on September 11, 2003

Late asthmatic reactions induced by inhalation of allergen-derived T-cell peptides

F. Runa Ali1, William L.G. Oldfield1, Noritaka Higashi2, Mark Larche1, and A. Barry Kay1*

1 Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, United Kingdom, 2 Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa, Japan

* To whom correspondence should be addressed. E-mail: a.b.kay{at}imperial.ac.uk.

In atopic asthmatics allergen-derived T cell peptides injected intradermally induce isolated late asthmatic reactions (LAR) followed by bronchial hyporesponsiveness to peptide, inhibition of the allergen-induced cutaneous latephase reaction (LPR) and altered T cell function in vitro. Experimental animal data indicates that "activation" and "tolerance" also occur if peptides are inhaled. In this study we show that inhalation of Fel d 1-derived peptides induced isolated LAR in cat-allergic asthmatics comparable to that previously demonstrated using intradermal injection. LAR's were accompanied by eosinophilia and non-significant elevations of total cysteinyl leukotrienes in the sputum. Unlike the intradermal route, repeated inhalation of peptides was not associated with abrogation of the LAR and produced a sputum eosinophilia comparable to the first exposure. Additionally, there was no inhibition of the cutaneous LPR to whole cat dander. Thus, isolated LAR induced by inhaled, allergen-derived peptides represent a novel model of provoked asthma, and are not associated with the induction of hyporesponsiveness ("tolerance") in the skin or lung. Some of the results of these studies have been previously reported in the form of abstracts (1,2).
Key words: allergy, T lymphocytes, epitopes, inflammation, tolerance




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