TY - JOUR
T1 - Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice
AU - Chapoval, Svetlana P.
AU - Nabozny, Gerald H.
AU - Marietta, Eric V.
AU - Raymond, Ernie L.
AU - Krco, Christopher J.
AU - Andrews, Amy G.
AU - David, Chella S.
PY - 1999/6
Y1 - 1999/6
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI6175
DO - 10.1172/JCI6175
M3 - Article
C2 - 10377177
AN - SCOPUS:0032716602
SN - 0021-9738
VL - 103
SP - 1707
EP - 1717
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -