CD137-mediated immunotherapy for allergic asthma

Tobias Polte, Juergen Foell, Christoph Werner, Heinz Gerd Hoymann, Armin Braun, Stefan Burdach, Robert S. Mittler, Gesine Hansen

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

80 Zitate (Scopus)

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-γ. While B lymphocytes are partly depleted, the number of CD8+ T cells is increased. Blockade of IFN-γ 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 allergic asthma, and they indicate CD137 as a possible target for therapeutic intervention in this disease.

OriginalspracheEnglisch
Seiten (von - bis)1025-1036
Seitenumfang12
FachzeitschriftJournal of Clinical Investigation
Jahrgang116
Ausgabenummer4
DOIs
PublikationsstatusVeröffentlicht - 1 Apr. 2006

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