Distant lymph nodes serve as pools of Th1 cells induced by neonatal BCG vaccination for the prevention of asthma in mice

Allergy. 2013 Mar;68(3):330-8. doi: 10.1111/all.12099. Epub 2013 Jan 25.

Abstract

Background: Neonatal Bacillus Calmette-Guérin (BCG) vaccination induces vigorous T-helper type 1 (Th1) responses and inhibits allergy-related airway dysfunction, but the exact mechanisms remain unclear. The objective of this study was to address where the Th1 cells induced by neonatal BCG vaccination are generated and stored, and how they are recruited into the inflamed airway for the prevention of allergen-induced airway inflammation.

Methods: We vaccinated neonatal C57BL/6 mice with BCG in a mouse model of asthma and analyzed the expression and function of Th1 cells in vivo and in vitro.

Results: BCG vaccination-induced Th1 cells in the local inguinal lymph nodes (ILN) migrated into the lungs upon inhaled ovalbumin (OVA) challenge in OVA-sensitized mice. These CD4(+) T cells in the ILN exhibited potentials of activation, proliferation and cytokine secretion and expressed high levels of CXCR3. Adoptive transfer of CD4(+) T cells from BCG-treated ILN significantly decreased allergic airway responses. In addition, the protective effect of BCG vaccination against allergic airway inflammation was lost upon the excision of the ILN.

Conclusions: These data demonstrate that ILN serves as a 'weapon' pool of Th1 cells following BCG vaccination, and these cells are ready for the migration into the inflamed lungs upon the allergen challenge, thereby inhibiting allergen-induced airway disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / immunology*
  • Asthma / prevention & control*
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Movement / immunology
  • Chemokine CXCL9 / metabolism
  • Female
  • Immunization
  • Lung / immunology
  • Lung / pathology
  • Lymph Nodes / immunology*
  • Male
  • Mice
  • Ovalbumin / immunology
  • Phenotype
  • Receptors, CXCR3 / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Allergens
  • BCG Vaccine
  • Chemokine CXCL9
  • Receptors, CXCR3
  • Ovalbumin