Abstract
Background: Allergic bronchopulmonary aspergillosis (ABPA) is a lung hypersensitivity disease mediated in part by CD4+ TH2 cells. There is a significant association between ABPA and the HLA-DR2 genotypes DRB1*1501 and DRB1*1503, whereas resistance might be associated with HLA-DRB1*1502. Objective: We sought to elucidate the role of HLA-DR alleles in allergic inflammation in lungs. Methods: HLA-DR humanized transgenic mice expressing either the susceptible or resistant alleles were analyzed for the nature and extent of pulmonary inflammation after exposure to Aspergillus species antigens. Results: Exposed DRB1*1501 and DRB1*1503 transgenic mice displayed infiltrates made up prominently of eosinophils, which is consistent with the inflammation found in ABPA. The resistant DRB1*1502 mice, on the other hand, displayed minimal to moderate inflammation, consisting mainly of T-cell infiltrates. Significantly more mucin was produced in the DRB1*1503 and DRB1*1501 mice, and their ability to limit the number of Aspergillus species conidia within the lung parenchyma was impaired. Despite their differences, both the DRB1*1503 and DRB1*1502 strains mounted comparable T cell-proliferative responses to Aspergillus species antigens. Conclusion: The HLA-DR2 alleles DRB1*1501 and DRB1*1503 play a major role in the development of allergic pulmonary inflammation. In contrast, the HLA-DR2 allele DRB1*1502 mediates a nonallergic TH1-like response to the organism, possibly explaining an ABPA resistance factor. These results are in support of our published human studies in patients with cystic fibrosis and asthma. Clinical implications: HLA-DR typing in patients with cystic fibrosis and asthma will aid in the identification of individuals at risk for ABPA.
Original language | English (US) |
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Pages (from-to) | 570-577 |
Number of pages | 8 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 120 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- Allergic bronchopulmonary aspergillosis
- Aspergillus fumigatus
- HLA-DR
- MHC
- T2
- asthma
- cystic fibrosis
- eosinophilia
- pulmonary immunity
- transgenic
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology