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Titel (primär) CD137 ligand prevents the development of T-helper type 2 cell-mediated allergic asthma by interferon-γ-producing CD8+ T cells
Autor Polte, T.; Jagemann, A.; Foell, J.; Mittler, R.S.; Hansen, G.;
Journal / Serie Clinical and Experimental Allergy
Erscheinungsjahr 2007
Department IMMU;
Band/Volume 37
Heft 9
Sprache englisch;
Keywords allergy; co-stimulation; inflammation; lung; T cells
Abstract Background Allergic asthma is a T-helper type 2 (Th2) cell-mediated chronic disease that is characterized by airway hyperreactivity (AHR) and chronic eosinophilic airway inflammation. Several studies suggest co-stimulatory molecules like CD137 as potential targets for therapeutic interventions in allergic airway disease. Recently, we could show in a murine asthma model that administration of an agonistic antibody against the receptor of the co-stimulatory molecule CD137 prevented and even reversed an already-established asthma phenotype.Objective The purpose of this study was to analyse the effect of stimulation of the CD137 ligand by a monoclonal antibody (CD137L mAb).Methods To induce an asthma-like phenotype, BALB/c mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge. Anti-CD137L or control mAb were applied 1 day before OVA immunization or after the asthma phenotype was already established.Results Stimulation of the CD137L instead of the receptor by CD137L mAb prevents the development of an asthma-like phenotype but does not reverse established disease. While the receptor-mediated effect is partly mediated by anergy of CD4+ T cells and partly by induction of IFN-?-producing CD8+ T cells, the effect of the CD137L mAb is completely dependent on IFN-?-producing CD8+ T cells: blockade of IFN-? and depletion of CD8+ T cells fully abrogated the observed protective effect. In vitro experiments showed that the anti-CD137L mAb ligates directly to CD8+ T cells and induces the generation of IFN-? by this cell population.Conclusion Our results demonstrate that anti-CD137L mAb prevents disease development via IFN-?-producing CD8+ T cells but is inferior to stimulation of the receptor that reverses established disease by a mechanism including CD4+ T cell anergy.
ID 2164
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=2164
Polte, T., Jagemann, A., Foell, J., Mittler, R.S., Hansen, G. (2007):
CD137 ligand prevents the development of T-helper type 2 cell-mediated allergic asthma by interferon-γ-producing CD8+ T cells
Clin. Exp. Allergy 37 (9), 1374 - 1385