Accelerated induction of mycobacterial antigen-specific CD8+ T cells in the Mycobacterium tuberculosis-infected lung by subcutaneous vaccination with Mycobacterium bovis bacille Calmette-Guérin

Immunology. 2009 Dec;128(4):556-63. doi: 10.1111/j.1365-2567.2009.03141.x.

Abstract

Both CD4(+) and CD8(+) T cells are important in protection against Mycobacterium tuberculosis infection. To evaluate the effect of vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) on the CD8(+) T-cell response to pulmonary M. tuberculosis infection, we analyzed the kinetics of CD8(+) T cells specific to the mycobacterial Mtb32a(309-318) epitope, which is shared by M. tuberculosis and M. bovis BCG, in the lung of mice infected with M. tuberculosis. The CD8(+) T cells were detected by staining lymphocytes with pentameric major histocompatibility complex (MHC) class I H-2D(b-)Mtb32a(209-318) peptide complex and were analysed by flow cytometry. Mtb32a-specific CD8(+) T cells became detectable on day 14, and reached a plateau on day 21, in the lung of M. tuberculosis-infected unvaccinated mice. Subcutaneous vaccination with M. bovis BCG in the footpads induced Mtb32a-specific CD8(+) T cells in the draining lymph nodes (LNs) on day 7 and their numbers further increased on day 14. When M. bovis BCG-vaccinated mice were exposed to pulmonaryinfection with M. tuberculosis 4 weeks after vaccination, the Mtb32a-specific CD8(+) T cells in the infected lung became detectable on day 7 and reached a plateau on day 14, which was 1 week earlier than in the unvaccinated mice. The pulmonary CD8(+) T cells from the BCG-vaccinated M. tuberculosis-infected mice produced interferon-gamma in response to Mtb32a(209-318) peptide on day 7 of the infection, whereas those of unvaccinated mice did not. The results demonstrate that induction of mycobacterial antigen-specific protective CD8(+) T cells in the M. tuberculosis-infected lung is accelerated by subcutaneous vaccination with M. bovis BCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Bacterial / immunology
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Injections, Subcutaneous
  • Interferon-gamma / biosynthesis
  • Lung / immunology*
  • Lymph Nodes / immunology
  • Mediastinum
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / immunology
  • Tuberculosis, Pulmonary / immunology*
  • Vaccination / methods

Substances

  • Antigens, Bacterial
  • BCG Vaccine
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Interferon-gamma