Respiratory infections are the third leading cause of death worldwide. Illness is caused by pathogen replication and disruption of airway homeostasis by excessive expansion of cell numbers. One strategy to prevent lung immune–mediated damage involves reducing the cellular burden. To date, antiinflammatory strategies have affected both antigen-specific and naive immune repertoires. Here we report a novel form of immune intervention that specifically targets recently activated T cells alone. OX40 (CD134) is absent on naive T cells but up-regulated 1–2 d after antigen activation. OX40–immunoglobulin fusion proteins block the interaction of OX40 with its ligand on antigen-presenting cells and eliminate weight loss and cachexia without preventing virus clearance. Reduced proliferation and enhanced apoptosis of lung cells accompanied the improved clinical phenotype. Manipulation of this late costimulatory pathway has clear therapeutic potential for the treatment of dysregulated lung immune responses.
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20 October 2003
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October 20 2003
A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
Ian R. Humphreys,
Ian R. Humphreys
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
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Gerhard Walzl,
Gerhard Walzl
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
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Lorna Edwards,
Lorna Edwards
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
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Aaron Rae,
Aaron Rae
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
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Sue Hill,
Sue Hill
2Xenova Research Ltd., Cambridge CB4 0WG, United Kingdom
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Tracy Hussell
Tracy Hussell
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
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Ian R. Humphreys
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
Gerhard Walzl
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
Lorna Edwards
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
Aaron Rae
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
Sue Hill
2Xenova Research Ltd., Cambridge CB4 0WG, United Kingdom
Tracy Hussell
1Centre for Molecular Microbiology and Infection (CMMI), Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AZ, United Kingdom
Address correspondence to Tracy Hussell, CMMI, Biological Sciences, Imperial College of Science, Technology and Medicine, Exhibition Road, London SW7 2AZ, United Kingdom. Phone: 44-207-5943091; Fax: 44-207-5943095; email: [email protected]
Abbreviations used in this paper: BAL, bronchoalveolar lavage fluid; BrdU, 5-bromo-2′-deoxyuridine; HA, hemagglutinin; MLN, mediastinal LN; OX40L, OX40 ligand; RT, room temperature.
Received:
March 05 2003
Revision Received:
August 19 2003
Accepted:
September 16 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (8): 1237–1242.
Article history
Received:
March 05 2003
Revision Received:
August 19 2003
Accepted:
September 16 2003
Citation
Ian R. Humphreys, Gerhard Walzl, Lorna Edwards, Aaron Rae, Sue Hill, Tracy Hussell; A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection . J Exp Med 20 October 2003; 198 (8): 1237–1242. doi: https://doi.org/10.1084/jem.20030351
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