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

The Journal of Allergy and Clinical Immunology
C TangE H Walters

Abstract

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. 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. Peripheral blood CD4(+) T cells and AMs were cocultured under different conditions. 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. Lower IL-12 production by the AMs from asthmatic subjects was also observed under the same conditions. Allergen-related T-cell IFN-gamma 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 wa...Continue Reading

Citations

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