Aberrant Expression of NKG2D Ligand and High Expression HLA-Ⅰ Molecules May Contribute to Immune Escape from Natural Killer Cell-mediated Immune Surveillance of Malignant Gliomas
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Graphical Abstract
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Abstract
Objective To explore the mechanism of immune escape from natural killer(NK)cell-mediated immune surveillance of malignant gliomas. Methods We took K562 cells cytolysis sensitively to NK cell as positive control,cytotoxicities of NK cells isolated from 5 healthy volunteers against U251 cells were analyzed by LDH releasing assay at different effector-to-target cell ratios(E∶T).The genes and proteins expression of NKG2D ligands on K562 and U251 cell line were respectively measured by RT-PCR and flow cytometry.In blocking experiment s, mAbs of different N KG2D ligands and HLA2 Ⅰmolecules were added to the target cells at E∶T of 20∶1. Results Cytotoxicity of N K cells against K562 cells was much higher than that against U251 cells at the same ET ratio. There was a significant difference between them. The genes of N KG2D ligands were positive in K562 and U251 cells, All the proteins of N KG2D ligands were expressed on K562 cell surface, but noly ULBP2 molecule was found on U251 cell surface. In blocking experiment s, the cytotoxicity of N K cells against K562 cell was partially inhibited, that against U251 cell was not influenced when mAbs of different N KG2D ligands were added ; the cytotoxicity of N K cells against U251 cell was dramatically upgraded, that against K562 cell was not influenced when mAb of HLA2 Ⅰmolecules was added. Conclusion Aberrant expression of N KG2D ligand and high expression HLA2 Ⅰmolecules may cont ribute to immune escape f rom N K cell2mediated immune surveillance of malignant gliomas.
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