Cockroach allergen-induced eosinophilic airway inflammation in HLA-DQ/human CD4(+) transgenic mice

Airway eosinophilic inflammation is a characteristic feature of allergic as thma. Exposure to allergens produced by the German cockroach (Blattella ger manica) is a risk factor for allergic disease in genetically predisposed in dividuals, and has been linked to an increase in asthma morbidity among coc kroach-sensitive inner city children. To determine the role and contributio n of specific HLA class II in the pathogenesis of allergic airway Inflammat ion in cockroach-induced asthma, we generated double-transgenic, double-kno ckout mice expressing human HLA-DQ8, HLA-DQ6, and CD4 molecules in the abse nce of mouse class II and mouse CD4. Mice were actively Immunized and later challenged intranasally with cockroach allergen extract. These mice develo ped bronchoalveolar lavage fluid (BALF) eosinophilia and pulmonary eosinoph ilia. This was accompanied by an increase in total protein levels, IL-5, an d IL-13 in BALF. There were also elevated levels of cockroach-specific seru m IgG1 and total serum IgE. Histological analysis revealed peribronchial an d perivascular eosinophilic inflammation in cockroach-treated mice. Other p athologic changes in the airways were epithelial cell hypertrophy and mucus production. Treatment with anti-DQ mAb significantly reduced pulmonary and BALF eosinophilia in cockroach allergen-sensitized mice. A beta (0) mice a nd transgenic mice expressing human CD4 molecule alone (without class II) o r human HLA-DQ8 molecule (without CD4) treated in the same fashion showed n o eosinophilia In bronchoalveolar fluid and no pulmonary parenchymal inflam mation. Our results provide direct evidence that HLA-DQ molecules and CD4 T cells mediate cockroach-induced eosinophilic inflammation in the airways.