We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance.
- Authors
Oppenheim, David E; Roberts, Scott J; Clarke, Sarah L; Filler, Renata; Lewis, Julie M; Tigelaar, Robert E; Girardi, Michael; Hayday, Adrian C
- Abstract
Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'immunoevasion'. Investigating this paradox, we report here that constitutive Rae-1epsilon transgene expression in normal epithelium elicited local and systemic NKG2D downregulation, generalized but reversible defects in NK cell-mediated cytotoxicity and mild CD8(+) T cell defects. The extent of NKG2D downregulation correlated well with the incidence and progression of cutaneous carcinogenesis, emphasizing the utility of NKG2D as a marker of tumor resistance. Thus, NKG2D engagement is a natural mediator of immunosurveillance, which can be compromised by locally sustained ligand expression but potentially restored by innate immune activation.
- Publication
Nature immunology, 2005, Vol 6, Issue 9, p928
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1239