Possible roles of KIR2DL4 expression on uNK cells in human pregnancy.
OBJECTIVE
To investigate possible roles of the natural killer (NK) cell receptor killer immunoglobulin-like receptor (KIR)2DL4 expressed on uterine NK (uNK) cells during pregnancy, we investigated KIR2DL4 expression on uNK cells isolated from patients with early recurrent spontaneous abortion (RSA) and normal early pregnancy women, and functions of KIR2DL4 was analyzed in vitro. METHODS OF THE STUDY: Semi-quantitative RT-PCR analysis was introduced to detect KIR2DL4 messenger RNA (mRNA) expression on uNK cells. Cytotoxicity and cytokine production as the result of interaction of KIR2DL4 and its ligand human leukocyte antigen (HLA)-G were analyzed in vitro with lactic dehydrogenase releasing method and enzyme-linked immunosorbent assay, respectively.


RESULTS
No significant difference in KIR2DL4 mRNA expression was observed, while the KIR2DL4 protein level in isolated uNK cells is much higher in normal controls than that in RSA patients. Data showed that HLA-G transfection could not reverse the lysis of uNK against HLA-G transfected K562 cells but induced cytokine production. Furthermore, we demonstrated that, via KIR2DL4, membrane-bound HLA-G could induce high cytotoxicity and cytokine production in a high cytotoxic, IL-2 dependent human NK cell line NK-92 cells.


CONCLUSIONS
Our data suggest that KIR2DL4 might play a crucial implication for human pregnancy.
Yan
Wei-Hua
WH
Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, People's Republic of China. yanwhcom@yahoo.com
Lin
Aifen
A
Chen
Bao-Guo
BG
Zhou
Mei-Ying
MY
Dai
Mei-Zhen
MZ
Chen
Xue-Jiao
XJ
Gan
Ling-Hong
LH
Zhu
Min
M
Shi
Wei-Wu
WW
Li
Bo-Li
BL
D000026:Abortion, Habitual / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C515079:KIR2DL4 protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4