Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation

PLoS One. 2012;7(7):e40314. doi: 10.1371/journal.pone.0040314. Epub 2012 Jul 9.

Abstract

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Airway Remodeling / immunology
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / therapy*
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Cytokines / blood
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / physiology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / physiology
  • T-Lymphocytes, Regulatory / transplantation
  • Transforming Growth Factor beta / physiology

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Transforming Growth Factor beta
  • Ovalbumin