NK1.1+ cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis

J Immunol. 2012 Jul 15;189(2):897-905. doi: 10.4049/jimmunol.1102833. Epub 2012 Jun 18.

Abstract

We previously found that human NK cells lyse Mycobacterium tuberculosis-infected monocytes and alveolar macrophages and upregulate CD8(+) T cell responses. We also found that human NK cells produce IL-22, which inhibits intracellular growth of M. tuberculosis, and that NK cells lyse M. tuberculosis-expanded CD4(+)CD25(+)FOXP3(+) T regulatory cells (Tregs). To determine the role of NK cells during the protective immune response to vaccination in vivo, we studied the NK cell and T cell responses in a mouse model of vaccination with bacillus Calmette-Guérin (BCG), followed by challenge with virulent M. tuberculosis H37Rv. BCG vaccination enhanced the number of IFN-γ-producing and IL-22-producing NK cells. Depletion of NK1.1(+) cells at the time of BCG vaccination increased the number of immunosuppressive Tregs (CD4(+)CD25(hi), 95% Foxp3(+)) after challenge with M. tuberculosis H37Rv, and NK1.1(+) cells lysed expanded but not natural Tregs in BCG-vaccinated mice. Depletion of NK1.1(+) cells at the time of BCG vaccination also increased the bacillary burden and reduced T cell responses after challenge with M. tuberculosis H37Rv. IL-22 at the time of vaccination reversed these effects and enhanced Ag-specific CD4(+) cell responses in BCG-vaccinated mice after challenge with M. tuberculosis H37Rv. Our study provides evidence that NK1.1(+) cells and IL-22 contribute to the efficacy of vaccination against microbial challenge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukins / biosynthesis
  • Interleukins / physiology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / microbiology
  • Lymphocyte Count
  • Mice
  • Mycobacterium bovis / immunology*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*

Substances

  • Interleukins
  • Tuberculosis Vaccines
  • Interferon-gamma
  • interleukin-22