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The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma

The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma
The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma
Background: T cells play an important role in airway inflammation in asthma through the release of TH2 cytokines. Optimal T-cell activation by antigen-presenting cells requires co-stimulatory signaling, such as the interaction of CD80, CD86, or both with CD28. In patients with mild allergic asthma, the fusion protein cytotoxic T-lymphocyte antigen 4Ig (CTLA-4Ig), which inhibits CD28-mediated signaling, blocks the release of IL-5 and IL-13 from bronchial explant cultures exposed to the allergen Dermatophagoides pteronyssinus.

Objectives: To assess costimulation in more severe forms of atopic asthma, we have compared the ability of CTLA-4Ig to block allergen-induced cytokine responses of bronchial explants and PBMCs from patients with moderately severe asthma.

Methods: Bronchial explants and PBMCs were cultured in vitro, and cytokine expression was measured by means of quantitative RT-PCR and ELISA.

Results: Constitutive mRNA transcripts for IL-5, IL-13, and GM-CSF were detected in the tissue explants, but only IL-5 mRNA increased significantly with allergen stimulation. Consistent with increased transcription, allergen-stimulated IL-5 protein release into explant supernatants, but this was not blocked by CTLA-4Ig. Allergen did not induce GM-CSF release, and IL-13 protein could not be detected in the explant supernatants under any condition. In contrast, allergen enhanced production of IL-5 and IL-13 by PBMC cultures from the same subjects, and this was inhibited effectively by CTLA-4Ig.

Conclusions: These data suggest that IL-5 production in the airways of subjects with moderately severe asthma is largely independent of CD28-mediated costimulation. The different requirements for CD28-mediated costimulation in PBMC cultures and bronchial tissue cultures emphasizes the importance of the tissue microenvironment in pulmonary inflammatory responses in severe asthma.
asthma, costimulation, ctla4, cd28, t cell, allergen, explant, inflammation, il
0091-6749
976-981
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Corkhill, Andrea
d46c1129-bbe5-4c67-9ab2-36edb93e0ba4
Jaffar, Zeina
0b883e4c-3943-4c7e-a303-ecdc0916ce13
Roberts, Kevan
2cf2d2f6-7911-41f9-a03e-5cf7735d7480
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Corkhill, Andrea
d46c1129-bbe5-4c67-9ab2-36edb93e0ba4
Jaffar, Zeina
0b883e4c-3943-4c7e-a303-ecdc0916ce13
Roberts, Kevan
2cf2d2f6-7911-41f9-a03e-5cf7735d7480
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Lordan, James L., Davies, Donna E., Wilson, Susan J., Dent, Gordon, Corkhill, Andrea, Jaffar, Zeina, Roberts, Kevan, Djukanovic, Ratko and Holgate, Stephen T. (2001) The role of CD28-B7 costimulation in allergen-induced cytokine release by bronchial mucosa from patients with moderately severe asthma. Journal of Allergy and Clinical Immunology, 108 (6), 976-981. (doi:10.1067/mai.2001.119740).

Record type: Article

Abstract

Background: T cells play an important role in airway inflammation in asthma through the release of TH2 cytokines. Optimal T-cell activation by antigen-presenting cells requires co-stimulatory signaling, such as the interaction of CD80, CD86, or both with CD28. In patients with mild allergic asthma, the fusion protein cytotoxic T-lymphocyte antigen 4Ig (CTLA-4Ig), which inhibits CD28-mediated signaling, blocks the release of IL-5 and IL-13 from bronchial explant cultures exposed to the allergen Dermatophagoides pteronyssinus.

Objectives: To assess costimulation in more severe forms of atopic asthma, we have compared the ability of CTLA-4Ig to block allergen-induced cytokine responses of bronchial explants and PBMCs from patients with moderately severe asthma.

Methods: Bronchial explants and PBMCs were cultured in vitro, and cytokine expression was measured by means of quantitative RT-PCR and ELISA.

Results: Constitutive mRNA transcripts for IL-5, IL-13, and GM-CSF were detected in the tissue explants, but only IL-5 mRNA increased significantly with allergen stimulation. Consistent with increased transcription, allergen-stimulated IL-5 protein release into explant supernatants, but this was not blocked by CTLA-4Ig. Allergen did not induce GM-CSF release, and IL-13 protein could not be detected in the explant supernatants under any condition. In contrast, allergen enhanced production of IL-5 and IL-13 by PBMC cultures from the same subjects, and this was inhibited effectively by CTLA-4Ig.

Conclusions: These data suggest that IL-5 production in the airways of subjects with moderately severe asthma is largely independent of CD28-mediated costimulation. The different requirements for CD28-mediated costimulation in PBMC cultures and bronchial tissue cultures emphasizes the importance of the tissue microenvironment in pulmonary inflammatory responses in severe asthma.

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More information

Published date: 2001
Keywords: asthma, costimulation, ctla4, cd28, t cell, allergen, explant, inflammation, il

Identifiers

Local EPrints ID: 27234
URI: https://eprints.soton.ac.uk/id/eprint/27234
ISSN: 0091-6749
PURE UUID: d71ba3ef-c57f-4501-81ed-45ab5109a9fc
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 27 Apr 2006
Last modified: 24 May 2019 00:39

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Contributors

Author: James L. Lordan
Author: Donna E. Davies ORCID iD
Author: Susan J. Wilson
Author: Gordon Dent
Author: Andrea Corkhill
Author: Zeina Jaffar
Author: Kevan Roberts

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