Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus.
OBJECTIVE
To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE).


METHODS
Patients with SLE (n=108), rheumatoid arthritis (RA; n=90), Behçet's disease (n=39), or ankylosing spondylitis (n=41) and healthy control subjects (n=173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription-polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro.


RESULTS
Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RA patients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLE patients, but not RA patients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLE patients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLE patients.


CONCLUSIONS
In SLE patients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE.
Park
Yong-Wook
YW
Chonnam National University Medical School, and Chonnam National University Hospital, Gwangju, Republic of Korea. parkyw@jnu.ac.kr
Kee
Seung-Jung
SJ
Cho
Young-Nan
YN
Lee
Eun-Hee
EH
Lee
Hwa-Youn
HY
Kim
Eun-Mi
EM
Shin
Min-Ho
MH
Park
Jeong-Jin
JJ
Kim
Tae-Jong
TJ
Lee
Shin-Seok
SS
Yoo
Dae-Hyun
DH
Kang
Hyung-Sik
HS
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology; D001528:Behcet Syndrome / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000473:pathology / Q000502:physiology; D007694:Killer Cells, Natural / Q000473:pathology* / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000473:pathology* / Q000503:physiopathology*; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000473:pathology / Q000503:physiopathology; D013921:Thrombocytopenia / Q000473:pathology / Q000503:physiopathology
D015375:Receptors, Interleukin-2; D054353:Perforin; D053804:Granzymes