Regulatory natural killer cells in murine liver and their immunosuppressive capacity.
BACKGROUND
Abundant amounts of natural killer (NK) cells are present in the liver, most of which are endowed with direct cytotoxic and inflammatory cytokine production capacities. However, the control of compromised immunity in the liver may be accomplished by a population of regulatory NK cells possessing suppressive or tolerogenic functions.


OBJECTIVE
To identify and characterize regulatory NK cells in murine liver.


METHODS
NK cells were isolated from the liver of C57BL/6 mice by magnetic-activated cells sorting (MACS). NK cells were stimulated with different agents and those cells that produced interleukin (IL)-10 were detected by flow cytometry and isolated by MACS. IL-10-producing NK cells were regarded as regulatory NK cells and the functional capacities of liver-derived regulatory NK cells were assessed in vitro.


RESULTS
The frequencies of regulatory NK cells in the liver were 4.1 +/- 0.3% of hepatic NK cells and 0.45 +/- 0.02% of liver nonparenchymal cells. Regulatory NK cells produced abundant amounts of IL-10 in culture. These cells also suppressed the proliferative capacities of T cells and B cells in vitro. However, another population of NK cells that did not produce IL-10 (immunogenic NK cells) could not suppress lymphocyte proliferation.


CONCLUSIONS
The presence of regulatory NK cells in the liver and their immunosuppressive capacities endowed these cells with the critical function of maintaining homeostasis under normal conditions. Exaggerated or impaired functions of these cells may also contribute to different pathological processes.
Yoshida
Osamu
O
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
Akbar
Sheikh Mohammad Fazle
SM
Chen
Shiyi
S
Miyake
Teruki
T
Abe
Masanori
M
Murakami
Hidetaka
H
Hiasa
Yoichi
Y
Onji
Morikazu
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10; D007371:Interferon-gamma