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

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.