Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation

Ruth S.S. Arestides, Hongzhen He, Robert M. Westlake, Andy I. Chen, Arlene H. Sharpe, David L. Perkins, Patricia W. Finn

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

T cell activation and cytokine secretion are important mediators of inflammation in allergic asthma. The costimulatory pathway CD28/CD80/CD86 has been shown to play an important role in T cell activation in allergic asthma, but less is known about the effect of other costimulatory molecules in allergy. The costimulatory molecule OX40 ligand (OX40L), a member of the tumor necrosis factor superfamily, has been shown to be important in T cell priming and cytokine production. We investigated the role of OX40L in a murine model of allergic inflammation using OX40L-/- mice. In this model, following OVA sensitization and challenge, mice develop features of allergic inflammation including elevated levels of total serum IgE, pulmonary eosinophils, cytokines, and pulmonary inflammation. In the absence of OX40L, total serum IgE, pulmonary eosinophils, cytokines, and pulmonary inflammation were all significantly reduced compared to wild-type controls. Levels of eotaxin mRNA, an eosinophil-specific chemoattractant, were also markedly reduced, paralleling the significant reduction in pulmonary eosinophils. Levels of allergen-induced Th1 as well as Th2 cytokines were also significantly reduced. Together, the data support a critical role for OX40L signals in allergic responses.

Original languageEnglish (US)
Pages (from-to)2874-2880
Number of pages7
JournalEuropean Journal of Immunology
Volume32
Issue number10
DOIs
StatePublished - Oct 2002
Externally publishedYes

Keywords

  • Allergy
  • Asthma
  • Costimulation
  • Cytokine
  • OX40 ligand

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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