| Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma. | |
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MedLine Citation:
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PMID: 11344354 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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C Tang; C Ward; D Reid; R Bish; P M O'byrne; E H Walters |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2001-05-09 Completed Date: 2001-06-21 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 863-70 Citation Subset: AIM; IM |
Affiliation:
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Department of Respiratory Medicine, Alfred Hospital, and Monash University, Melbourne, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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pharmacology Antigens, CD / immunology Antigens, CD40 / immunology* Antigens, CD80 / immunology Antigens, CD86 Asthma / immunology* Bronchial Provocation Tests Bronchoscopy Coculture Techniques HLA-DR Antigens / analysis Humans 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* |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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