Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice
Svetlana P. Chapoval, … , Amy G. Andrews, Chella S. David
Svetlana P. Chapoval, … , Amy G. Andrews, Chella S. David
Published June 15, 1999
Citation Information: J Clin Invest. 1999;103(12):1707-1717. https://doi.org/10.1172/JCI6175.
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Article

Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice

Abstract

The human leukocyte antigen (HLA) restriction of the IgE response to different allergens in humans has been a subject of numerous published studies. However, the role and contribution of specific HLA class II molecules in the pathogenesis of allergic airway inflammation are unknown and difficult to assess. HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous mouse class II gene expression were actively immunized and later challenged intranasally with short ragweed (SRW) allergenic extract. The HLA-DQ transgenic mice developed pulmonary eosinophilia and lung tissue damage. We also found an increase in total protein (TP) level and IL-5 production in bronchoalveolar lavage (BAL) fluid and an increase in SRW-specific Th2-type immunoglobulins (IgG1, IgG2b) and total serum IgE levels. Under similar treatment, DQ-negative full-sib control mice were normal. The allergic response could be significantly inhibited or abrogated in HLA-DQ mice by systemic treatment with anti-DQ mAb. The in vivo responses of HLA-DQ6 and HLA-DQ8 mice showed differences in terms of levels of eosinophilia, BAL protein, IL-5 concentration, and lung hyperreactivity to inhaled methacholine. These findings demonstrate the crucial role for specific HLA-DQ molecules in SRW-specific CD4+ T-cell activation and resulting recruitment of eosinophils into the airways.

Authors

Svetlana P. Chapoval, Gerald H. Nabozny, Eric V. Marietta, Ernie L. Raymond, Christopher J. Krco, Amy G. Andrews, Chella S. David

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Figure 1

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Representative examples of BAL fluid cells isolated from PBS-treated HLA...
Representative examples of BAL fluid cells isolated from PBS-treated HLA-DQ or H-2Aβ0 mice (a), SRW-sensitized and -challenged H-2Aβ0 (b) and HLA-DQ6 (c) mice, and anti-DQ–treated SRW-immunized HLA-DQ6 mice (d) 48 hours after intranasal challenge with allergenic extract. No eosinophils were recovered in BAL from any groups of PBS-treated mice (a) or SRW-sensitized and -challenged MHC class II knockout mice (b). Eosinophils were found to dominate the cellular infiltrate into BAL of HLA-DQ6 and HLA-DQ8 transgenic mice (c). Only a few eosinophils can be seen in anti-DQ–treated SRW-immunized mice (d). e, eosinophils; l, lymphocytes; m, macrophages.