A critical role for OX40 in T cell-mediated immunopathology during lung viral infection

Humphreys, Ian R. ORCID: https://orcid.org/0000-0002-9512-5337, Walzl, Gerhard, Hussell, Tracy and Hill, Sue 2003. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. Journal of Experimental Medicine 198 (8) , pp. 1237-42. 10.1084/jem.20030351

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Additional Information:	Publisher’s copyright requirements: “Ownership of copyright in the Work remains with the authors. The Authors retain the non-exclusive right to do anything they want with the Work, so long as the Authors provide attribution to the place of original publication. The retained right specifically includes the right to post the Work on the authors’ or their institutions’ web sites.” See: http://www.rupress.org/site/subscriptions/terms.xhtml
Publisher:	Rockefeller University Press
ISSN:	15409538
Last Modified:	17 May 2023 02:43
URI:	https://orca.cardiff.ac.uk/id/eprint/252

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