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A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection

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, antiinflam...

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Detalles Bibliográficos
Autores principales: Humphreys, Ian R., Walzl, Gerhard, Edwards, Lorna, Rae, Aaron, Hill, Sue, Hussell, Tracy
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194232/
https://www.ncbi.nlm.nih.gov/pubmed/14568982
http://dx.doi.org/10.1084/jem.20030351
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author Humphreys, Ian R.
Walzl, Gerhard
Edwards, Lorna
Rae, Aaron
Hill, Sue
Hussell, Tracy
author_facet Humphreys, Ian R.
Walzl, Gerhard
Edwards, Lorna
Rae, Aaron
Hill, Sue
Hussell, Tracy
author_sort Humphreys, Ian R.
collection PubMed
description 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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spelling pubmed-21942322008-04-11 A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection Humphreys, Ian R. Walzl, Gerhard Edwards, Lorna Rae, Aaron Hill, Sue Hussell, Tracy J Exp Med Article 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. The Rockefeller University Press 2003-10-20 /pmc/articles/PMC2194232/ /pubmed/14568982 http://dx.doi.org/10.1084/jem.20030351 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Humphreys, Ian R.
Walzl, Gerhard
Edwards, Lorna
Rae, Aaron
Hill, Sue
Hussell, Tracy
A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title_full A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title_fullStr A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title_full_unstemmed A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title_short A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection
title_sort critical role for ox40 in t cell–mediated immunopathology during lung viral infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194232/
https://www.ncbi.nlm.nih.gov/pubmed/14568982
http://dx.doi.org/10.1084/jem.20030351
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