Table 1.

In vivo models demonstrating that chronic exposure to NKG2DLs results in receptor down-regulation.

Experimental Mouse Model	Findings	Reference
Nonobese diabetic (NOD) mice	NKG2D down-modulation on activate NK cells Impaired NKG2D-dependent NK cell functions	[47]
FVB transgenic mice overexpressing Rae-1ε ligand ubiquitously or localized in normal epithelium	NKG2D down-modulation on splenic NK cells (and intraepithelial T cells) Impaired NKG2D-dependent NK cell functions Normal generation of antigen (HY) specific CTL memory Increased susceptibility to tumorigenesis	[48]
C57BL/6 transgenic mice constitutively and ubiquitously overexpressing MICA	NKG2D down-modulation on splenic NK cells Impaired NKG2D-dependent functions in vivo and in vitro Impaired CD8 T cell response to L. monocytogeneses	[49]
C57BL/6 transgenic mice ubiquitously overexpressing Rae-1ε ligand	NKG2D down-modulation on splenic NK cells Impaired NKG2D-dependent NK cell functions Normal NK and CD8 T cell response to MCMV	[60]

NKG2D, natural-killer receptor group 2, member D; NK, natural killer; CTL, cytotoxic T lymphocytes; MCMV, murine cytomegalovirus.