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[Immunoediting of natural killer cells by human nasopharyngeal carcinoma cell line: altered expression of KIRs and NKG2D receptors leads to reduction of natural killer cell-mediated cytolysis].
Nan Fang Yi Ke Da Xue Xue Bao 2007; 27(3):247-9NF

Abstract

OBJECTIVE

To analyze the changes of inhibitory killer cell immunoglobulin-like receptors (KIRs), NKG2D receptor and the cytotoxicity of natural killer (NK) cells induced by persistent exposure to CNE2 cells.

METHODS

The HLA-class I genotypes of CNE2 cells and KIR genotypes were determined by PCR with sequence-specific primers (PCR-SSP). The expressions of KIR2DL1, KIR2DL3, KIR3DL1, and NKG2D by the NK cells (freshly isolated NK cells, NK cells cocultured with 100 U/ml IL2 or with 100 U/ml IL2 and CNE2 cells as the control, IL2 and CNE2 groups, respectively) were analyzed by flow cytometry. Cytotoxicity of NK cells against CNE2 cells were detected by LDH releasing assay.

RESULTS

The HLA genotypes of CNE2 cells were A2, 24, B18, 35, Cw4, 7. NK cells isolated from 3 healthy donors expressed KIR2DL1, KIR2DL3, and KIR3DL1. After 4, 24 and 48 h of culture, NK cells in CNE2 group displayed higher KIR2DL1, KIR2DL3 but lower NKG2D expression than those in the control and IL2 groups (P<0.01), whereas the latter two groups showed no significant difference in KIR2DL1, KIR2DL3, and NKG2D expressions (P>0.05), and no difference in KIR3DL1 expression was found between the 3 groups (P>0.05). After 24 h of culture, the cytotoxicity against CNE2 cells mediated by the NK cells in IL2 and CNE2 groups were (26.96-/+1.47) % and (2.74-/+1.64) % at E:T ratios of 10:1, and (35.74-/+3.59)% and (4.57-/+2.41) % at E:T ratio of 20:1, respectively. NK cells in CNE2 group displayed lower cytotoxicity than those in IL2 group (P<0.01).

CONCLUSIONS

Persistent exposure to tumor cells expressing NKG2D ligands can lead to downregulated expression of NKG2D receptor, increased expression of KIRs and reduction of NK-mediated cytolysis. These results elucidate the molecular mechanism of reduced cytotoxicity mediated by the edited NK cells and indicate that blocking HLA-class I-bound KIRs or enhancing the expression of NKG2D may promote NK cell-mediated cytolysis.

Authors+Show Affiliations

Department of Pathology, Southern Medical University, Guangzhou 510515, China. gzyuan@pub.guangzhou.gd.cnNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

17425963

Citation

Guo, Kun-yuan, et al. "[Immunoediting of Natural Killer Cells By Human Nasopharyngeal Carcinoma Cell Line: Altered Expression of KIRs and NKG2D Receptors Leads to Reduction of Natural Killer Cell-mediated Cytolysis]." Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University, vol. 27, no. 3, 2007, pp. 247-9.
Guo KY, Mei JZ, Yao KT. [Immunoediting of natural killer cells by human nasopharyngeal carcinoma cell line: altered expression of KIRs and NKG2D receptors leads to reduction of natural killer cell-mediated cytolysis]. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27(3):247-9.
Guo, K. Y., Mei, J. Z., & Yao, K. T. (2007). [Immunoediting of natural killer cells by human nasopharyngeal carcinoma cell line: altered expression of KIRs and NKG2D receptors leads to reduction of natural killer cell-mediated cytolysis]. Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University, 27(3), pp. 247-9.
Guo KY, Mei JZ, Yao KT. [Immunoediting of Natural Killer Cells By Human Nasopharyngeal Carcinoma Cell Line: Altered Expression of KIRs and NKG2D Receptors Leads to Reduction of Natural Killer Cell-mediated Cytolysis]. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27(3):247-9. PubMed PMID: 17425963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Immunoediting of natural killer cells by human nasopharyngeal carcinoma cell line: altered expression of KIRs and NKG2D receptors leads to reduction of natural killer cell-mediated cytolysis]. AU - Guo,Kun-yuan, AU - Mei,Jia-zhuan, AU - Yao,Kai-tai, PY - 2007/4/12/pubmed PY - 2008/5/13/medline PY - 2007/4/12/entrez SP - 247 EP - 9 JF - Nan fang yi ke da xue xue bao = Journal of Southern Medical University JO - Nan Fang Yi Ke Da Xue Xue Bao VL - 27 IS - 3 N2 - OBJECTIVE: To analyze the changes of inhibitory killer cell immunoglobulin-like receptors (KIRs), NKG2D receptor and the cytotoxicity of natural killer (NK) cells induced by persistent exposure to CNE2 cells. METHODS: The HLA-class I genotypes of CNE2 cells and KIR genotypes were determined by PCR with sequence-specific primers (PCR-SSP). The expressions of KIR2DL1, KIR2DL3, KIR3DL1, and NKG2D by the NK cells (freshly isolated NK cells, NK cells cocultured with 100 U/ml IL2 or with 100 U/ml IL2 and CNE2 cells as the control, IL2 and CNE2 groups, respectively) were analyzed by flow cytometry. Cytotoxicity of NK cells against CNE2 cells were detected by LDH releasing assay. RESULTS: The HLA genotypes of CNE2 cells were A2, 24, B18, 35, Cw4, 7. NK cells isolated from 3 healthy donors expressed KIR2DL1, KIR2DL3, and KIR3DL1. After 4, 24 and 48 h of culture, NK cells in CNE2 group displayed higher KIR2DL1, KIR2DL3 but lower NKG2D expression than those in the control and IL2 groups (P<0.01), whereas the latter two groups showed no significant difference in KIR2DL1, KIR2DL3, and NKG2D expressions (P>0.05), and no difference in KIR3DL1 expression was found between the 3 groups (P>0.05). After 24 h of culture, the cytotoxicity against CNE2 cells mediated by the NK cells in IL2 and CNE2 groups were (26.96-/+1.47) % and (2.74-/+1.64) % at E:T ratios of 10:1, and (35.74-/+3.59)% and (4.57-/+2.41) % at E:T ratio of 20:1, respectively. NK cells in CNE2 group displayed lower cytotoxicity than those in IL2 group (P<0.01). CONCLUSIONS: Persistent exposure to tumor cells expressing NKG2D ligands can lead to downregulated expression of NKG2D receptor, increased expression of KIRs and reduction of NK-mediated cytolysis. These results elucidate the molecular mechanism of reduced cytotoxicity mediated by the edited NK cells and indicate that blocking HLA-class I-bound KIRs or enhancing the expression of NKG2D may promote NK cell-mediated cytolysis. SN - 1673-4254 UR - https://www.unboundmedicine.com/medline/citation/17425963/[Immunoediting_of_natural_killer_cells_by_human_nasopharyngeal_carcinoma_cell_line:_altered_expression_of_KIRs_and_NKG2D_receptors_leads_to_reduction_of_natural_killer_cell_mediated_cytolysis]_ L2 - http://www.diseaseinfosearch.org/result/5110 DB - PRIME DP - Unbound Medicine ER -