TY - JOUR
T1 - Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation
AU - Arestides, Ruth S.S.
AU - He, Hongzhen
AU - Westlake, Robert M.
AU - Chen, Andy I.
AU - Sharpe, Arlene H.
AU - Perkins, David L.
AU - Finn, Patricia W.
PY - 2002/10
Y1 - 2002/10
N2 - 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.
AB - 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.
KW - Allergy
KW - Asthma
KW - Costimulation
KW - Cytokine
KW - OX40 ligand
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U2 - 10.1002/1521-4141(2002010)32:10<2874::AID-IMMU2874>3.0.CO;2-4
DO - 10.1002/1521-4141(2002010)32:10<2874::AID-IMMU2874>3.0.CO;2-4
M3 - Article
C2 - 12355440
AN - SCOPUS:0036772373
SN - 0014-2980
VL - 32
SP - 2874
EP - 2880
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -