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
; 42(9): 2459-70, 2012 Sep.
Article
in En
| MEDLINE
| ID: mdl-22736333
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-ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
BCG Vaccine
/
Killer Cells, Natural
/
Receptors, Immunologic
/
Antigens, CD34
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Cytotoxicity, Immunologic
/
Mycobacterium bovis
Language:
En
Journal:
Eur J Immunol
Year:
2012
Document type:
Article
Affiliation country:
Italy