Understanding of heterogeneous nature of natural killer (NK) subsets and their developmental origins are important for the study of NK cell biology, and for the application of NK cell-based therapies in the treatment of cancers. Here we demonstrate that the surface expression of CD94 can divide murine NK cells into two distinct and approximately even CD94low and CD94high subsets in all tested organs and tissues (n \#8805; 3). When compared to CD94low NK cells, murine CD94high NK cells have a significantly greater capacity to proliferate (p = 0.018, n = 11), to produce IFN-\#947; (p = 0.007, n = 3), and to lyse target cells (p = 0.04, n = 6). The CD94high subset also has higher surface expression of CD117, CD69, and CD127, and lower expression of Ly49D (activating) as well as Ly49G2 (inhibitory) (p< 0.05, n = 5). In vivo, purified murine CD94low NK cells develop into CD94high NK cells, but not vice versa (n = 3). Human CD94 allows for further phenotypic and functional dissection of the CD56dim NK subset which comprises ~90% of human NK in blood. Human CD94highCD56dim NK cells produce significantly more IFN-\#947; (p = 0.04, n \#8805; 3), and this appears to be secondary to a substantially greater degree of STAT4 phosphorylation in the CD94highCD56dim NK cells compared to CD94lowCD56dim NK cells (n = 3). Interestingly, these two human subsets show no significant differences in cytotoxic activity against standard targets. Collectively, we believe that CD94 is a relevant developmental marker that phenotypically and functionally defines both murine and human NK subsets. The CD94high NK cells likely play an important role in tumor surveillance, due to their potent capabilities of IFN-\#947; production and cytotoxcity.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4154.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO