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After 2 weeks, the mice were perfused and the brains were evaluated by immunostaining to characterize the survival and phenotype of the GFP+ transplanted cells. The total number of surviving GFP+ NPCs was quantified using unbiased stereology and the fraction of NPCs adopting a neuronal fate was estimated by confocal colocalization of GFP with Dcx and NeuN. The survival of GFP+ cells was increased by loss of NKG2D (Fig. 6C, p �� .05). Allografts in NKG2D-/- hosts showed significantly more neurogenesis than WT hosts, with three times more transitional and mature neurons expressing NeuN (Fig. 6D, p http://www.selleckchem.com/products/XL184.html Neurogenesis in NKG2D-/- mice receiving NPC allografts is restored to levels comparable to that seen in WT animals receiving syngeneic transplants. Similar results were observed in NKG2D-/- hosts that received syngeneic grafts. Most GFP+ neurons in the WT hosts expressed Dcx only whereas a significant fraction of graft-derived cells in NKG2D-/-hosts also coexpressed NeuN (Fig. 6D, 6F, 6G), suggesting that NKG2D-mediated effects were most pronounced on neurons of a slightly more mature phenotype. To determine if this result is consistent with Rae-1 expression on neurons of varying maturation states, NPCs were differentiated in vitro for 7 days and analyzed for class III ��-tubulin (Tuj1), Map2ab, and Rae-1 expression on days 4 and 7 by immunofluorescent staining and flow cytometry. Early progenitors and newborn neurons, expressing Tuj1 and no Map2 on day 4, express moderate to high levels of Rae1 (Fig. http://www.selleckchem.com/products/CP-690550.html 6E, left panels). By day 7, maturing neurons expressing Map2 and reduced Tuj1 show diminished Rae1 expression, consistent with previous reports that analyzed Rae expression levels in the developing and adult brain (Fig. 6E, right panels) [[26, 35]]. NPC and other stem cell-like transplants in the CNS have long been thought to benefit from immune privilege [[3, 36, 37]], resulting from reduced or no MHC expression and the CNS environment. The CNS tightly regulates leukocyte entry and adaptive immune recognition [[3, http://www.selleck.cn/products/MLN8237.html 38]] and the absence of MHC is beneficial for evasion of adaptive immune responses. However, the absence of MHC also triggers a ��Missing-self�� response by NK cells of the innate immune system [29]. Still, several reports have indicated that NPC, as well as other stem cell populations, are resistant to NK cell lysis [[9, 39]]. In contrast, we have demonstrated that NK cells target both syngeneic and allogeneic NPC as efficiently as they target the NK-sensitive mouse lymphoma line, YAC-1. Other reports have shown the susceptibility of embryonic stem cell (ESC) and induced pluripotent stem cell lines to NK-mediated lysis [42], indicating that innate recognition and killing is not unique to CNS transplantation.