CD137-mediated immunotherapy for allergic asthma
Tobias Polte, … , obert S. Mittler,, Gesine Hansen
Tobias Polte, … , obert S. Mittler,, Gesine Hansen
Published April 3, 2006
Citation Information: J Clin Invest. 2006;116(4):1025-1036. https://doi.org/10.1172/JCI23792.
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Research Article Immunology

CD137-mediated immunotherapy for allergic asthma

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.

Authors

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

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Figure 5

Therapeutic effect of anti-CD137 mAb on airway remodeling.

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Therapeutic effect of anti-CD137 mAb on airway remodeling. BALB/c mice w...
BALB/c mice were immunized with OVA on day 1 and challenged with OVA intranasally several times according to reversal protocol II (Figure 1), described in Methods. After application of anti-CD137 mAb or control mAb on day 32, mice were challenged again with OVA on days 39–41. On day 43, mice were sacrificed. (A) MSB-stained lung tissues (magnification, ×400) from BALB/c mice revealed increased peribronchiolar ECM deposition, which was reduced by anti-CD137 mAb. (B) For quantification of ECM deposition, digital photographs of 4 bronchioles per tissue section were taken and analyzed with a computer-based image-analyzing program, demonstrating the protective effect of anti-CD137 mAb. (C) Total lung collagen was increased in OVA-immunized mice compared with control animals. This effect was partly abrogated (62%) by anti-CD137 mAb application. *P < 0.05, OVA plus anti-CD137 mAb versus OVA plus control antibody by Student’s t test. n ≥ 8 animals per group; data are expressed as mean ± SEM from 2 independent experiments.