CD137-mediated immunotherapy for allergic asthma

The Journal of Clinical Investigation
Tobias PolteG Hansen

Abstract

The prevalence of asthma continues to increase. Asthma is caused by a Th2 cell-driven immune response. Its optimal treatment remains a challenge, and a sufficient immunotherapeutic approach to treating asthma has yet to be found. Using a murine asthma model, we show that a single injection of an anti-CD137 (4-1BB) mAb prevents the development of airway hyperreactivity, eosinophilic airway inflammation, excessive mucus production, and elevated IgE during the observation period of 7 weeks. Most importantly, even established disease is completely reversed by anti-CD137 mAb administration. The protection is associated with markedly reduced Th2 cytokine production and increased secretion of the Th1 cytokine IFN-gamma. While B lymphocytes are partly depleted, the number of CD8+ T cells is increased. Blockade of IFN-gamma and depletion of CD8+ T cells during treatment with anti-CD137 mAb reduces in part but does not abrogate the protective effect of CD137 mAb. In contrast, CD137 mAb-mediated CD4+ T cell anergy is critical for the observed effects, since transfer of CD4+ T cells from CD137 mAb-treated mice conveyed protection. These data demonstrate, for the first time to our knowledge, the capacity of anti-CD137 mAb to ameliorate alle...Continue Reading

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Citations

Mar 5, 2013·Veterinary Immunology and Immunopathology·Xinxin ZhaoXun Suo
Mar 26, 2009·Nature Reviews. Immunology·Michael Croft
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Mar 3, 2010·American Journal of Respiratory and Critical Care Medicine·Nicole SchützeTobias Polte
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Nov 13, 2008·The Journal of Allergy and Clinical Immunology·Tobias PolteGesine Hansen
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Jan 29, 2010·Immune Network·Byungsuk Kwon

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Methods Mentioned

BETA
bronchoalveolar lavage
FACS
lavage
light microscopy
ELISA

Software Mentioned

HistoClick

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