Year 2

Our goal is to identify strategies to improve the engraftment of stem cell transplants in patients. During the previous funding years, we have demonstrated that a small subset of white blood cells called natural killer (NK) cells are involved in the rejection of embryonic stem cells in animal models. However, we have now shown that not all NK cells have the same potential to reject embryonic stem (ES) cells. NK cells which express receptors that can bind a molecule called MHC are termed “licensed” because they have a greater ability to kill virally-infected and tumor cells. However, we have now demonstrated for the first time that these cells are also the predominant subset of NK cells which are involved in the rejection of ES cells. This may lead to clinical strategies to improve ES engraftment since we have identified a key player in the rejection of these cells. Furthermore, we have studied how NK cells can act as “veto” cells: cells which can attack the T and NK cells in the patient which are responsible for rejecting transplants. Combined, our studies suggest that NK cells from both the donor and patient can be utilized and carefully observed in stem cell transplants to improve the likelyhood of engraftment and clinical responses.