T lymphocytes in asthma: Bronchial versus peripheral responses

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Presentation transcript:

T lymphocytes in asthma: Bronchial versus peripheral responses Stephen R. Durham, MD, FRCP, Stephen J. Till, PhD, Christopher J. Corrigan, PhD, MRCP Journal of Allergy and Clinical Immunology Volume 106, Issue 5, Pages S221-S226 (November 2000) DOI: 10.1067/mai.2000.110154 Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 Serum IL-2R concentration in patients with acute severe asthma versus control groups. The dotted line represents the 95% confidence interval for the range of values in normal control subjects. COAD , Chronic obstructive airway disease. (From Corrigan CJ, Kay AB. CD4 T-lymphocyte activation in acute severe asthma: relationship to disease severity and atopic status. Am Rev Respir Dis 1990;141:970-7. With permission. Official Journal of the American Thoracic Society. © American Lung Association.) Journal of Allergy and Clinical Immunology 2000 106, S221-S226DOI: (10.1067/mai.2000.110154) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 Proliferation and IL-5 production by peripheral blood T-cell cultures in patients with asthma and sensitive allergy to house dust mite (AA ), in patients with allergic rhinitis (AR ), in atopic asymptomatic patients (AASY ), and in nonatopic normal control subjects (N ). Peripheral blood monocytes were cultured for 6 days in the presence of optimal concentrations of house dust mite before the measurement of IL-5 production in culture supernatants by enzyme-linked immunosorbent assay and tritiated thymidine incorporation. (From Till S, Dickason R, Huston D, Humbert M, Robinson D, Larche M, et al. IL-5 secretion by allergen-stimulated CD4+ T cells in primary culture: relationship to expression of allergic disease. J Allergy Clin Immunol 1997;99:563-9. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S221-S226DOI: (10.1067/mai.2000.110154) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 T-cell activation, IL-5 mRNA expression, bronchoalveolar eosinophilia, and the magnitude of the late-phase asthmatic response (LPR ) in bronchoalveola of atopic asthmatic patients after allergen inhalation challenge. Patients were challenged with house dust mite or grass pollen extract. Twenty-four hours later, fiberoptic bronchoscopy and BAL were performed. CD25 expression on T cells was measured by flow cytometry. Eosinophils and IL-5 mRNA expression were detected with immunostaining and in situ hybridization of BAL cytospin preparations, respectively. The late-phase asthmatic response was recorded as maximal fall in FEV1 at 3 to 24 hours after the challenge. Correlations among cell counts and the late-phase asthmatic response were determined by the Spearman’s rank method. (Adapted with permission from Durham SR, Kay AB. Late allergic responses. In: Kaplan AP, ed. Allergy. 2nd ed. Philadelphia, PA: WB Saunders; 1997:292.) Journal of Allergy and Clinical Immunology 2000 106, S221-S226DOI: (10.1067/mai.2000.110154) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 The influence of prednisolone tablets (0.6 mg/kg daily) versus placebo on airway methacholine responsiveness, the numbers of IL-5 mRNA+ cells, and the number of eosinophils in the BAL fluid that was harvested before and 2 weeks after treatment. Between-group differences (after/before treatment) were significant for methacholine PC20, for IL-5 mRNA+ cells, and for eosinophils. Two-tailed Mann-Whitney U test probability values are shown. (Adapted with permission from Robinson D, Hamid Q, Ying S, Bentley A, Assoufi B, Durham S, et al. Prednisolone treatment in asthma is associated with modulation of bronchoalveolar lavage cell interleukin-4, interleukin-5, and interferon-γ cytokine gene expression. Am Rev Respir Dis 1993;148:401-6. Official Journal of the American Thoracic Society. © American Lung Association.) Journal of Allergy and Clinical Immunology 2000 106, S221-S226DOI: (10.1067/mai.2000.110154) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 5 Hypothesis of the mechanism of allergen-induced late asthmatic response as a consequence of TH2-type T-lymphocyte activation. Whereas corticosteroids inhibit TH2-cytokine production, allergen injection immunotherapy may act by inducing T-cell unresponsiveness (anergy) and/or immune deviation in favor of TH1 responses. APC , Antigen-presenting cell. Journal of Allergy and Clinical Immunology 2000 106, S221-S226DOI: (10.1067/mai.2000.110154) Copyright © 2000 Mosby, Inc. Terms and Conditions