Naslov
ENHANCED NK CELL-DEPENDENT SURVEILLANCE OF TUMOURS IN NKG2D-DEFICIENT MICE

Autori
Jelenčić, Vedrana ; Wensveen, Felix Martinus ; Lenartić, Maja ; Polić, Bojan ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
17th FEBS Summer School on Immunology: "Genes, Receptors and Regulation"

Mjesto i datum
Rabac, Hrvatska, 14.09.2013. - 21.09.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
NKG2D; NCR1; NK cdlls; B16

Sažetak
NKG2D is an activating receptor expressed on all NK cells, activated / memory CD8 T cells, NKT and γδ T cells. We have shown previously that NKG2D-deficiency alters NK cell development and function (Zafirova et al., Immunity, 2009). NKG2D deficient NK cells showed enhanced proliferation in the immature phase, perturbation in size of NK cell subpopulations and augmented sensitivity to apoptosis. Furthermore, we observed enhanced NK cell-mediated resistance to MCMV infection in NKG2D-deficient mice which is due to the enhanced maturation and hyper responsiveness of NK cells. Here we questioned whether and how NKG2D-deficiency influences control of melanoma (B16) cells which do not express NKG2D-ligands, but do express ligands for other activating NK receptors. Surprisingly, we observed prolonged survival of NKG2D-/- mice subjected to B16 cells in comparison to C57BL/6 controls. Their survival was NK-cell mediated since NK cell depletion abrogated the difference. Next we questioned which activating NK receptor is responsible for the enhanced control. One of the obvious candidates was NCR1, since B16 cells express ligands for this receptor expressed on all NK cells. To investigate potential role of NCR1 we employed NCR1- deficient (NCR1 gfp/gfp) and double knock-out (NKG2D-/-NCR gfp/gfp) mice. The enhanced control of the melanoma tumour in NKG2D-/- mice was completely abrogated when double k.o. mice were used, indicating for a dominant role of NCR1 on NKG2D-/- NK cells. In conclusion, NKG2D-deficiency results in NK cells with better capabilities in controlling B16 melanoma cells and this control is NCR1-dependet. Our findings indicate interplay between NKG2D and NCR1, two activating receptors involved early in the development and function of NK cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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