Generation of IgE-specific cytotoxic T lymphocytes as a novel immunotherapeutic approach for the treatment of allergic asthma

Singapore Med J. 2020 Apr;61(4):212-220. doi: 10.11622/smedj.2019068. Epub 2019 Jul 11.

Abstract

Introduction: Overproduction of immunoglobulin E (IgE) by a subset of B cells plays a key role in the pathogenesis of allergic asthma. Anti-IgE monoclonal antibodies have been successfully used to treat the disease, but long-term application is required.

Methods: For this study, cytotoxic T lymphocytes (CTLs) against IgE-producing B cells were generated ex vivo by stimulating naive CD8 T cells with IgE-derived peptides presented by Drosophila-derived artificial antigen-presenting cells. Based on the treatment of allergic asthma in mice, the inhibitive effect of this CTL on IgE responses and airway inflammation was determined with the enzyme-linked immunosorbent assay and histochemical method.

Results: The IgE-specific CTLs effectively lysed target cells in vitro, while the adoptively transferred CTLs specifically inhibited IgE responses and airway inflammation in an asthmatic mouse model. The effect of IgE-specific CTLs is MHC (major histocompatibility complex) Class I-restricted and requires the expression of perforin.

Conclusion: IgE-specific CTLs generated ex vivo may provide a novel treatment for allergic asthma and lead to a new therapy for other immunological disorders.

Keywords: artificial antigen-presenting cells; cytotoxic T lymphocytes; immunoglobulin E; perforin.

MeSH terms

  • Animals
  • Asthma / therapy*
  • Disease Models, Animal
  • Hypersensitivity
  • Immunoglobulin E / immunology*
  • Immunotherapy / methods*
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Immunoglobulin E