Document Detail

Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma.
MedLine Citation:
PMID:  11344354     Owner:  NLM     Status:  MEDLINE    
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. 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 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 lower expression of CD40 rather than B7-1 signals on the AMs from these patients.
C Tang; C Ward; D Reid; R Bish; P M O'byrne; E H Walters
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  107     ISSN:  0091-6749     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-09     Completed Date:  2001-06-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  863-70     Citation Subset:  AIM; IM    
Department of Respiratory Medicine, Alfred Hospital, and Monash University, Melbourne, Australia.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antigens, CD / immunology
Antigens, CD40 / immunology*
Antigens, CD80 / immunology
Antigens, CD86
Asthma / immunology*
Bronchial Provocation Tests
Coculture Techniques
HLA-DR Antigens / analysis
Hypersensitivity, Immediate / immunology*
Interferon-gamma / secretion
Interleukin-12 / antagonists & inhibitors,  immunology,  pharmacology
Interleukin-5 / secretion
Macrophages, Alveolar / immunology*,  pathology
Membrane Glycoproteins / antagonists & inhibitors,  immunology
Methacholine Chloride / diagnostic use
Recombinant Proteins / immunology,  pharmacology
Signal Transduction
Th2 Cells / immunology*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, CD40; 0/Antigens, CD80; 0/Antigens, CD86; 0/CD86 protein, human; 0/HLA-DR Antigens; 0/Interleukin-5; 0/Membrane Glycoproteins; 0/Recombinant Proteins; 187348-17-0/Interleukin-12; 62-51-1/Methacholine Chloride; 82115-62-6/Interferon-gamma

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