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Xenograft animal models using immunodeficient mice have been widely applied in medical research on various human diseases. NOD/Shi-scirf-IL2rγnull (NOG) mice are known to show an extremely high engraftment rate of xenotransplants compared with conventional immunodeficient mice. This high engraftment rate of xenotransplants in NOG mice was substantially suppressed by the transfer of spleen cells from NOD-sci'rf mice that were devoid of NK cells. These results indicate that cell types other than splenic NK cells present in NOD-scirf mice but not in NOG mice may be involved in this suppression. To identify the cell types responsible for this effect, we transferred subpopulations of spleen cells from NOD-vtiW mice into NOG mice and assessed the levels of human cell engraftment after human PBMC (hPBMC) transplantation. These experiments revealed that CDIlc+B220+ plasmacytoid dendritic cells (pDCs) from NOD-saW mice markedly inhibited engraftment of human cells. The CDllc+B220+ CD122+ cells further fractionated from the pDCs based on the expression of CD122, which is an NK cell marker strongly inhibited during hPBMC engraftment in NOG mice. Moreover, the CD122+ cells in the pDC fraction were morphologically distinguishable from conventional CD122+ NK cells and showed a higher rejection efficiency. The current results suggest that CDllc+B220+ CD122+ cells play an important role in xenograft rejection, and their absence in NOG mice may be critical in supporting the successful engraftment of xenotransplants. [ABSTRACT FROM AUTHOR]