engleski

NKG2D deficiency results in better control of melanoma

NKG2D and NCR are both activating receptors expressed on all murine NK cells early in NK cell development. For NKG2D receptor majority of its’ ligands are known, such as Rae 1 family, H60 and MULT, while for NCR receptor most of the ligands are still unknown. It has been published that NKG2D deficient NK cells show perturbation in size of some NK cell subpopulations, impairments in NK cell development, enhanced proliferation of NK cells and augmented sensitivity to apoptosis. NKG2D deficient mice show an enhanced NK cell-mediated resistance to MCMV infection. NKG2D deficient mice are also less responsive to tumor targets expressing NKG2D ligands. However, ability of NKG2D deficient mice to control tumors which don’t express NKG2D ligands is still unknown. In our model we are using B16 melanoma cell line, which does not express NKG2D ligands. We observed prolonged survival of NKG2D-/- mice in comparison to wild type mice. Prolonged survival of NKG2D deficient mice is result of NK cell activity since after NK cell depletion these differences were lost. Although B16 cells don’t express NKG2D ligands they expresses unknown NCR ligands, so to further analyse this observations we included in our study also NCR deficient mice ( NCRgfp/gfp) and double knock-out mice (NKG2D-/-NCRgfp/gfp). NKG2D deficient mice were the best in controling methastasis development while the NCRgfp/gfp mice were the worst. Same results were observed after MCMV infection at early time points (4th day post infection). Our findings indicate at possible interaction between these two receptors and show us that NKG2D deficiency results in hyperactive NK cells which are then better in controlling MCMV infection and tumor growth.

NKG2D; NCR1; B16 melanoma

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