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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Intranasal
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Allergens / administration & dosage*
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Allergens / immunology
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / pharmacology
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Antigens, Plant
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Blood Proteins / chemistry
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Bronchial Hyperreactivity / physiopathology
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / immunology
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CD4 Antigens / immunology
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Eosinophil Granule Proteins
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Epithelial Cells / pathology
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Gene Expression Regulation / immunology
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HLA-DQ Antigens / biosynthesis
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HLA-DQ Antigens / genetics*
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HLA-DQ Antigens / immunology
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Humans
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Immune Sera / biosynthesis
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Immunoglobulin E / blood
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Immunosuppressive Agents / pharmacology
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Interleukin-5 / metabolism
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Lymphocyte Activation / immunology
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Plant Proteins / administration & dosage*
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Plant Proteins / immunology
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Plant Proteins / pharmacokinetics
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Protein Biosynthesis
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Pulmonary Eosinophilia / etiology*
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Pulmonary Eosinophilia / genetics*
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Pulmonary Eosinophilia / immunology
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Pulmonary Eosinophilia / prevention & control
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Respiratory System / metabolism
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Ribonucleases*
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Staining and Labeling
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Allergens
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Amb a III protein, Ambrosia artemisiifolia
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Antibodies, Monoclonal
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Antigens, Plant
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Blood Proteins
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CD4 Antigens
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Eosinophil Granule Proteins
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HLA-DQ Antigens
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Immune Sera
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Immunosuppressive Agents
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Interleukin-5
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Plant Proteins
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Immunoglobulin E
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Ribonucleases