Receptor modulation and functional activation of human CD34+ Lin- -derived immature NK cells in vitro by Mycobacterium bovis Bacillus Calmette-Guerin (BCG)

Eur J Immunol. 2012 Sep;42(9):2459-70. doi: 10.1002/eji.201242375. Epub 2012 Jul 25.

Abstract

It is not yet clear whether immature NK (iNK) cells are bystanders to or rather participate in immune responses to pathogens that may colocalize in areas of NK-cell maturation such as bone marrow or lymph nodes. Mycobacteria, including Bacillus Calmette-Guerin (BCG), have been shown to interact with peripheral NK cells and in vivo may colocalize in areas of iNK-cell development. We studied infection with BCG of human cord blood CD34(+) Lin(-)-derived cultures containing myelomonocytes and iNK cells in vitro. Increased iNK-cell DNAM-1 expression, transient natural cytotoxicity receptor modulation, and production of IFN-γ were observed. Transcriptional receptor modulation was associated to BCG challenge, which determined increased iNK-cell cytotoxic activity against tumor cell lines and also increased killing of immature dendritic cells (iDCs). No requirement for cell contact was recorded for BCG-induced iNK-cell activation, while cytokine production including IL-18, IL-10, GM-CSF, and TGF-β contributed to the observed effects. Thus, iNK cells are affected by mycobacteria in vitro and may contribute to shaping of adaptive mature innate responses through iDC-iNK cross-talk. In addition, iNK-cell activation by BCG may represent a novel additional mechanism contributing to the effects observed upon BCG administration in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / genetics
  • Antigens, CD34 / immunology*
  • Antigens, CD34 / metabolism
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • BCG Vaccine / immunology*
  • Cytotoxicity, Immunologic / genetics
  • Cytotoxicity, Immunologic / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation
  • Monocytes / immunology
  • Monocytes / metabolism
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / immunology*
  • Mycobacterium bovis / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • T Lineage-Specific Activation Antigen 1
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens, CD34
  • Antigens, Differentiation, T-Lymphocyte
  • BCG Vaccine
  • T Lineage-Specific Activation Antigen 1
  • Interleukin-18
  • Receptors, Immunologic
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor