Requirements for allergen-induced airway inflammation and hyperreactivity in CD4- deficient and CD4-sufficient HLA-DQ transgenic mice Svetlana P. Chapoval,

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Presentation transcript:

Requirements for allergen-induced airway inflammation and hyperreactivity in CD4- deficient and CD4-sufficient HLA-DQ transgenic mice Svetlana P. Chapoval, MD, PhD, Eric V. Marietta, PhD, Michele K. Smart, MSc, Chella S. David, PhD Journal of Allergy and Clinical Immunology Volume 108, Issue 5, Pages 764-771 (November 2001) DOI: 10.1067/mai.2001.118794 Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 1 Cellular composition of BAL fluid (A ) and cytokine (B ) and EPO and histamine (C ) levels in BAL fluid supernatants of tg mice. A, Eosinophils dominate the cellular infiltrate into BAL of DQ+/hCD4+ and DQ6+ mice. *P < .03. ‡P < .05. B, SRW treatment resulted in the increase of IL-5 and IL-13 contents in DQ+/hCD4+ mice. C, EPO concentration was increased in DQ6+/hCD4+ and DQ8+/hCD4+ mice (*P < .05). *P < .05 in BAL histamine levels between either DQ8+ or DQ6+/hCD4+ mice and Aβ0/mCD40, hCD4+, DQ6+ tg mice. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 2 Histopathology of lung tissue. A, Lungs of DQ8+/hCD4+ mice showed a diffuse eosinophilic infiltration. B, There was no inflammation in lung tissue of Aβ0/mCD40 or hCD4+ mice. C, A perivascular eosinophil/MNC inflammation was observed in DQ6+ mice. D, Section of lung of DQ8+ mouse shows the absence of inflammatory cells. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 3 A, Histochemical staining with naphthol AS-D chloroacetate or toluidine blue reveals mast cells in the airway submucosa in either CD4-deficient or hCD4-sufficient DQ6+ and DQ8+ mice. B, Mast cells were also observed in sufficient numbers in other tg mice, the highest count being in DQ8+ mice. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 4 Respiratory system physiology of PBS-treated and SRW-sensitized and challenged tg mice (A ) and DQ+ mice (B ) treated with mAb during SRW treatment. A, Mean methacholine dose-response curves of 4 mice per control group and from 6 to 12 mice per experimental group (± SEM) are shown. B, Treatment of mice with anti-CD1, anti-NK1.1, or anti-CD8 mAb did not significantly attenuate hyperresponsiveness in comparison with control mAb–treated groups. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 5 Changes in blood eosinophil numbers in tg mice during SRW treatment. Results are expressed as means ± SEMs. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 6 Inhibition of SRW-specific proliferative response of spleen MNCs with mAb. The data represent the percentage of inhibition of [3H]thymidine incorporation in cultures with SRW. Δ counts-per-minute values for cultures with SRW alone are indicated. Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions

Fig. 7 Serum total IgE levels in tg mice. *P < .05 in comparison with IgE concentration in preimmune sera (day 0). Journal of Allergy and Clinical Immunology 2001 108, 764-771DOI: (10.1067/mai.2001.118794) Copyright © 2001 Mosby, Inc. Terms and Conditions