Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>NKG2D is an activating receptor expressed by all Natural Killer (NK) cells, a subset of T cells, and activated macrophages. NKG2D and its ligands, which are expressed on stressed or damaged cells, play important roles during viral infections, cancers, and autoimmune diseases, both in mouse and human. While NKG2D is well studied in NK cells, its function on other cells remains unclear, particularly in vivo. In this study, we examine the consequences of cell-specific ablation of NKG2D, or tissue-specific expression of its ligand Rae-1, on innate and adaptive immunity, using two novel mouse models. By crossing Cre expressing strains to our two newly generated mice bearing a floxed allele of NKG2D, or a Rosa26-LSL-Rae-1 transgene, we obtain conditional knockouts of NKG2D, or mice that express Rae-1 in a cell-specific manner. We are now able to dissect the contribution of each cell subset expressing NKG2D in models of viral infection, tumor rejection, and autoimmunity. In addition, we observed that NK cells chronically interact with myeloid cells in vivo, since expression of Rae-1 on these subsets, but not others, leads to down-modulation of NKG2D expression and impaired NKG2D-dependent functions. Data from these two new mouse models provide a better understanding of the role of NKG2D by defining its impact on different immune cell functions, and by mimicking physiopathological situations of patients in which a human counterpart of Rae-1 is expressed on various tissues.</jats:p>