Effect of KIR2DS1-mediated human natural killer cells cytotoxicity against leukemia cells
10.3760/cma.j.issn.1009-9921.2014.07.004
- VernacularTitle:KIR2DS1受体对人类NK细胞杀伤白血病细胞的作用研究
- Author:
Jing WANG
;
Tao GUAN
;
Jiangtao WANG
;
Liping SU
- Publication Type:Journal Article
- Keywords:
Natural killer cells;
Killer cell immunoglobulin-like receptors;
Human leucocyte antigen;
Acute leukemia;
Hematopoietic stem cell transplantation
- From:
Journal of Leukemia & Lymphoma
2014;23(7):393-396
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the killing effects of the killer cell immunoglobulin-like receptors (KIR) KIR2DS1-positive natural killer (NK) cells against leukemia cells.Methods High-purified NK cells separated by RosetteSep NK cell enrichment kit from healthy donor peripheral blood were taken as effector cells,and the freshly isolated bone marrow mononuclear cells from newly diagnosed acute myelogeneous leukemia (AML) patients were taken as target cells.The cytotoxic activity of NK cells were detected by CCK8 kit assay.HLA-Cw,KIR gene of the healthy donors and patients were detected by polymerase chain reaction and sequence specific primer (PCR-SSP) genotyping techniques,respectively.NK cells were divided into KIR2DS1-positive group and KIR2DS1-negevitive group,and then anti-KIR2DS1 mononuclear antibody was used to block KIR2DS1 of NK cells.Meanwhile based on HLA-Cw,KIR2DS1-positive NK cells and target cells were divided into C1 homozygote group(expressing HLA-Cw 01,03,07,08,12,14,16 alleles),C2 homozygote group (expressing HLA-Cw 02,04,05,06,15,17,18 alleles) and the C1/C2 heterozygote group (co-expressing the alleles in C1 group and C2 group).Results The purity of NK cells was (91.2±5.94) ％ through flow cytometry analysis.At the same effector-target ratio,cytotoxicity of KIR2DS1-positive NK cells against target cells was higher than that of KIR2DS1-negetive NK cells.While the E:T =10:1,cytotoxicity of KIR2DS1-positive NK cells against target cells [(2.82±6.81) ％] was significant higher than that of KIR2DS1-negetive NK cells [(28.61±5.14) ％] against target cells.The killing effects of KIR2DS1-positive NK cells was significantly weakened after KIR2DS1 blockaded with specific antibody (t =-3.00,P =0.05).When focusing on the C1 group NK cells,KIR2DS1-positive NK cells against C2 group [(4.39±3.46) ％] target cells was significantly higher than than against C1 group [(41.22±3.68) ％] (t =8.33,P ＜ 0.05) and C1/C2 group [(41.32±5.09) ％] (t =6.37,P ＜ 0.05) target cells.Conclusions The killing effects of KIR2DS1-positive NK cells are significantly higher than that of KIR2DS1-negetive NK cells.The HLA-C1 group KIR2DS1-positive NK cells could recognize HLA-C2 loci and then kill the target cells.
