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

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

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1707-1717
Number of pages11
JournalJournal of Clinical Investigation
Volume103
Issue number12
DOIs
StatePublished - Jun 1999

ASJC Scopus subject areas

  • Medicine(all)

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    Chapoval, S. P., Nabozny, G. H., Marietta, E. V., Raymond, E. L., Krco, C. J., Andrews, A. G., & David, C. S. (1999). Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice. Journal of Clinical Investigation, 103(12), 1707-1717. https://doi.org/10.1172/JCI6175