Evaluation of inducible costimulator/B7-related protein-1 as a therapeutic target in a murine model of allergic airway inflammation
| Autor: | Ryan E. Wiley, Susanna Goncharova, Manel Jordana, Theresa Shea, Jill R. Johnson, Anthony J. Coyle |
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| Rok vydání: | 2003 |
| Předmět: |
Pulmonary and Respiratory Medicine
Antigens Differentiation T-Lymphocyte Chemokine CCL11 Ovalbumin T cell Clinical Biochemistry Immunoglobulin E Bronchoalveolar Lavage Antibodies Inducible T-Cell Co-Stimulator Protein Inducible T-Cell Co-Stimulator Ligand Mice Th2 Cells Medicine Animals Molecular Biology Interleukin 5 Lung Interleukin 4 Cells Cultured Inflammation Mice Inbred BALB C Interleukin-13 biology business.industry Cell Biology respiratory system Th1 Cells Asthma Interleukin-10 Interleukin 10 Disease Models Animal medicine.anatomical_structure Desensitization Immunologic Chemokines CC Interleukin 13 Immunology biology.protein B7-1 Antigen Female Interleukin-4 Interleukin-5 business Spleen |
| Zdroj: | American journal of respiratory cell and molecular biology. 28(6) |
| ISSN: | 1044-1549 |
| Popis: | Given its primary role in the execution of T cell, and especially Th2, effector activity, the inducible costimulator (ICOS)/B7-related protein (RP)-1 costimulatory pathway is currently being heralded as a promising therapeutic target for immune-inflammatory disorders such as asthma. This study investigates the merits of ICOS blockade in a murine model of experimental asthma in which mice are sensitized to ovalbumin (OVA) through the respiratory mucosa. Intraperitoneal treatment of mice with anti-ICOS neutralizing antibody during sensitization resulted in a marked reduction in airway eosinophilia and IL-5 in bronchoalveolar lavage, but had no effect on interleukin (IL)-4, IL-13, and eotaxin content in bronchoalveolar lavage or the production of OVA-specific immunoglobulin E in serum. Cultured splenocytes from mice sensitized to OVA in the context of ICOS ablation produced enhanced levels of IL-4 and IL-5 upon stimulation with OVA, and this correlated with elevated inflammation and immunoglobulin E secretion upon long-term in vivo OVA recall; the deleterious effects ICOS blockade, however, were not associated with reduced IL-10 production by splenocytes. Peculiarly, anti-ICOS intervention during OVA rechallenge had no effect on airway inflammation or immunoglobulin production, despite high levels of ICOS expression on infiltrating CD4+ T cells. This study provides in vivo evidence of an exacerbated long-term immune-inflammatory response following acute ICOS blockade, and suggests that ICOS costimulation is functionally redundant in established allergic disease. |
| Databáze: | OpenAIRE |
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