Endothelial cells express NKG2D ligands and desensitize antitumor NK responses.

Chimeric mice in which RAE-1ε was present only in hematopoietic cells (WT → KO) showed high NKG2D levels comparable to KO → KO chimeras, indicating that hematopoietic RAE-1ε does not play a major role in engaging NKG2D, although there was a reproducibly small effect in most experiments that failed to reach significance.

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NK cell hyper-responsiveness in NKG2D-KO mice has been reported previously by several groups including ours ( Zafirova et al., 2009 ; Sheppard et al., 2013 ; Deng et al., 2015 ), although the trend of increased responsiveness did not reach statistical significance in our original characterization of the NKG2D-KO mouse ( Guerra et al., 2008 ).

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