Inhibition of allergen-induced airway remodeling by neonatal bacillus Calmette-Guerin vaccination is associated with interferon-gamma-producing T cells but not regulatory T cells in mice

Ann Allergy Asthma Immunol. 2011 Aug;107(2):163-70. doi: 10.1016/j.anai.2011.05.018. Epub 2011 Jun 15.

Abstract

Background: Epidemiological assessments of patients and studies using animal models show that exposure to Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine in early life prevents asthma development. However, little is known about the potential of neonatal BCG vaccination in preventing the development of airway remodeling of asthma.

Objective: To investigate the effects of multiple BCG vaccinations of neonates on the airway remodeling in mice and the accompanied pulmonary T cell responses.

Methods: BALB/c neonates were vaccinated with BCG 3 times. At 5 and 7 weeks of age, the mice were sensitized and then challenged with aerosolized ovalbumin (OVA) 3 times per week for 8 successive weeks. The extent of airway remodeling and induced pulmonary T cell responses were characterized.

Results: Multiple BCG vaccinations of neonates reduced OVA-induced remodeling events, including levels of peribronchial α-smooth muscle actin, peribronchial fibrosis, and airway epithelial mucin accumulation. The BCG vaccinations also decreased peribronchial cells expression of transforming growth factor beta 1 (TGF-β1). In contrast, BCG vaccinations increased the frequency of interferon-gamma (IFN-γ)-producing T cells in the lung and IFN-γ level in BALF, with no effects on pulmonary regulatory T cells and IL-17-producing T cells.

Conclusions: Our data suggest that multiple BCG vaccinations of neonates reduced metrics characteristic of allergen-induced airway remodeling. More importantly, this decrease was not associated with an increased number of pulmonary regulatory T cells but instead correlated with an increase of IFN-γ-producing T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling / immunology
  • Allergens / administration & dosage*
  • Animals
  • Animals, Newborn
  • Asthma / immunology*
  • Asthma / prevention & control
  • BCG Vaccine / administration & dosage*
  • Disease Models, Animal
  • Humans
  • Immunization
  • Interferon-gamma / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Allergens
  • BCG Vaccine
  • Interferon-gamma