Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:107

Article

Tang, CB ; Ward, C ; Reid, D ; Bish, R ; O'Byrne, PM ; Walters, EH

关键词: CD40;    B;    IL-12;    IL-5;    asthma;   

DOI  :  10.1067/mai.2001.114987

来源: Elsevier

【 摘 要 】

Background: We have previously shown that airway macrophages (AMs) from atopic nonasthmatic subjects, but not atopic asthmatic subjects, inhibit T-cell IL-5 production during an allergen-dependent interaction. However, the mechanisms responsible for the IL-5-modulating effect of the AMs are less clear. Objectives: The aim of the present study was to define the roles of B7 and CD40 costimulatory signals delivered by AMs in regulating T-cell IL-5 responses in an allergen-stimulated coculture system. Methods: Peripheral blood CD4(+) T cells and AMs were cocultured under different conditions. Results: Compared with those from well-matched atopic nonasthmatic subjects, AMs from atopic asthmatic subjects demonstrated a significantly lower expression of B7-1 and CD40, but not B7-2 and HLA-DR, after either fresh isolation or coculture with allergen-reactive CD4+ T cells. Lon:er IL-12 production by the AMs from asthmatic subjects was also observed under the same conditions. Allergen-related T-cell IFN-I and IL-5 production was inhibited by the addition of either neutralizing B7-1 or B7-2 antibody to the cocultures in both atopic groups. In contrast, IL-5 production was significantly increased by the addition of blocking CD40 antibody, whereas IL-12 production by the AMs was inhibited. Anti-IL 12 mAb enhanced IL-5 production in the cocultures from atopic nonasthmatic subjects, whereas a dose-dependent suppressive effect of recombinant human IL-12 on IL-5 production was seen in atopic asthmatic subjects. Conclusion: In this coculture model system, lower IL-12 production by AMs and higher IL-5 production by CD4(+) T cells in atopic asthmatic subjects compared with that found in atopic nonasthmatic subjects: are related to the loner expression of CD40 rather than B7-1 signals on the AMs from these patients.

【 授权许可】

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