Allergy Asthma Immunol Res.  2014 May;6(3):201-207. 10.4168/aair.2014.6.3.201.

Bacillus Calmette-Guerin Suppresses Asthmatic Responses via CD4+CD25+ Regulatory T Cells and Dendritic Cells

• Kim YJ
• Kim HJ
• Kang MJ
• Yu HS
• Seo JH
• Kim HY
• Park SJ
• Lee YC
• Hong SJ

• KMID: 2260681
• DOI: http://doi.org/10.4168/aair.2014.6.3.201

Abstract

PURPOSE
Bacillus Calmette-Guerin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma.
METHODS
BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb).
RESULTS
BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects.
CONCLUSIONS
BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs.

Keyword

BCG; dendritic cells; T-lymphocytes, regulatory; asthma; allergic inflammation; mouse

MeSH Terms

Animals
Asthma
Bacillus*
Bronchoalveolar Lavage
Dendritic Cells*
Eosinophils
Immunoglobulin E
Immunoglobulin G
Inflammation
Lung
Mice
Mycobacterium bovis
Ovalbumin
T-Lymphocytes, Regulatory*
Immunoglobulin E
Immunoglobulin G
Ovalbumin

Figure

• 

  Fig. 1 Effect of treatment with Bacillus Calmette-Guerin (BCG) vaccine-stimulated DCs on the ovalbumin (OVA)-induced allergic asthma of mouse model. OVA: mice sensitized with intraperitoneal injections of OVA on days 0 and 7 and then challenged with aerosolized OVA on days 14-16; Saline: mice sensitized and challenged with saline following the same time schedule described for OVA mice; BGC-DC: mice that were injected intravenously with BCG vaccine-stimulated DCs on day -5 and then sensitized and challenged with OVA; Non-DC: mice that were injected intravenously with unstimulated DCs on day -5 and then sensitized and challenged with OVA; BCG: mice injected intraperitoneally with BCG vaccine emulsified in alum and then sensitized and challenged with OVA (A) Brochial hyperresponsiveness (BHR), *P<0.05, **P<0.01 compared to the OVA mice; †P<0.01 compared to the BCG-DC-treated mice. (B) Differential cell counts in the Bronchoalvoelar lavage (BAL) fluid. (C) Lung pathology. (D) Peribronchial and perivascular lung inflammation scores. The values are the means±SD of the results from 5 mice per group. *P<0.05, **P<0.01.

• 

  Fig. 2 Effect of treatment with BCG vaccine-stimulated DCs on the serum levels of immunoglobulins in mouse model of allergic asthma. The plot legends are as described in Fig. 1. BCG vaccine-stimulated DC transfer inhibited total IgE, OVA-specific IgE and OVA- specific IgG1 levels compared to OVA mice. The values are the means±SD of the results from 5 mice per group. *P<0.05, **P<0.01.

• 

  Fig. 3 Effect of anti-CD25 monoclonal antibody (mAb) treatment on the allergic asthma of mice injected with BCG vaccine-stimulated DCs and then sensitized and challenged with OVA. The mice were injected intraperitoneally with anti-CD25 mAb before challenge with OVA. The plot legends are as described in Fig. 1 except that BCG-DC+ anti-CD25 indicate mice that received BCG-DCs and the anti-CD25 mAb. (A) BHR, *P<0.05, **P<0.01 compared to the OVA mice; †P<0.05 compared to the BCG-DC-treated mice. (B) Differential cell counts in the BAL fluid. (C) Lung pathology. (D) Peribronchial and perivascular lung inflammation scores. The values shown are the means±SD of the results from 5 mice per group. *P<0.05, **P<0.01.

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