Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice.
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.
Chapoval
S P
SP
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nabozny
G H
GH
Marietta
E V
EV
Raymond
E L
EL
Krco
C J
CJ
Andrews
A G
AG
David
C S
CS
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D052179:Antigens, Plant; D001798:Blood Proteins / Q000737:chemistry; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D047091:Eosinophil Granule Proteins; D004847:Epithelial Cells / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006683:HLA-DQ Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015848:Interleukin-5 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010940:Plant Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D014176:Protein Biosynthesis; D011657:Pulmonary Eosinophilia / Q000209:etiology* / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D012137:Respiratory System / Q000378:metabolism; D012260:Ribonucleases; D013194:Staining and Labeling; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; C028564:Amb a III protein, Ambrosia artemisiifolia; D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D001798:Blood Proteins; D015704:CD4 Antigens; D047091:Eosinophil Granule Proteins; D006683:HLA-DQ Antigens; D007106:Immune Sera; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D010940:Plant Proteins; D007073:Immunoglobulin E; D012260:Ribonucleases