Journal article
CTLA4Ig Inhibits Airway Eosinophilia and Hyperresponsiveness by Regulating the Development of Th1/Th2 Subsets in a Murine Model of Asthma
American journal of respiratory cell and molecular biology, Vol.18(4), pp.453-462
04/01/1998
DOI: 10.1165/ajrcmb.18.4.3055
PMID: 9533932
Abstract
Complete T-cell activation requires two distinct signals, one delivered via the T-cell receptor, and the second “co-stimulatory” signal through CD28/B7 ligation. Previous studies showed that the blockade of CD28/B7 ligation alters differentiation of Th1/Th2 lymphocyte subsets in vitro and in vivo. The present study was designed to determine the effect of a CD28/B7 antagonist (CTLA4Ig) on Th1/Th2 development in Schistosoma mansoni-sensitized and airway-challenged mice. Treatment of mice with CTLA4Ig beginning 1 wk after sensitization abolished airway responsiveness to intravenous methacholine determined 96 h following antigen challenge. We also found a significant reduction in bronchoalveolar lavage (BAL) eosinophilia, and reduced peribronchial eosinophilic infiltration and mucoid-cell hyperplasia. Furthermore, CTLA4Ig treatment significantly decreased interleukin (IL)-4 and IL-5 content in BAL fluid in vivo, and the production of IL-5 by lung lymphocytes stimulated with soluble egg antigen (SEA) in vitro. In contrast, the content of interferon-γ in BAL fluid and supernatant from SEA-stimulated lung lymphocytes from CTLA4Ig-treated mice was increased significantly compared with untreated animals. Thus, CTLA4Ig inhibits eosinophilic airway inflammation and airway hyperresponsiveness in S. mansoni-sensitized and airway-challenged mice, most likely due to attenuated secretion of Th2-type cytokines and increased secretion of Th1-type cytokines.
Details
- Title: Subtitle
- CTLA4Ig Inhibits Airway Eosinophilia and Hyperresponsiveness by Regulating the Development of Th1/Th2 Subsets in a Murine Model of Asthma
- Creators
- Philip A. Padrid - University of ChicagoMudit MathurXiantang LiKarin HerrmannYimin QinAshok CattamanchiJoel WeinstockDavid ElliottAnne I. SperlingJeffrey A. Bluestone
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.18(4), pp.453-462
- DOI
- 10.1165/ajrcmb.18.4.3055
- PMID
- 9533932
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 04/01/1998
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984359930902771
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