Prevention of embryo loss in non-obese diabetic mice using adoptive ITGA2+ISG20+ natural killer-cell transfer

Both regulatory T cells and regulatory natural killer (NK) cells may play essential roles in the maintenance of pregnancy. In this study, we show that a significantly high percentage of spontaneous embryo loss was observed in both allogeneic and syngeneic pregnant non-obese diabetic (NOD) mice. The percentage of embryo loss in allogeneic pregnant mice was further increased by the administration of anti-asialo ganglio-N-tetraosylceramide to deplete NK cells, but was decreased by the adoptive transfer of ITGA2(+)ISG20(+) (CD49b(+) CD25(+)) NK cells from normal mice. No such trend was observed in syngeneic pregnant NOD mice. The pattern of CXCR4 (specific receptor for CXCL12) expression on NK cells was analyzed and NK-cell migration was confirmed by in vitro and in vivo migratory assays. Since CXCL12 production by murine trophoblast cells was confirmed previously, our findings suggest that the recruitment of peripheral CXCR4-expressing ITGA2(+)ISG20(+) NK cells into pregnant uteri may be important in the regulation of feto-maternal tolerance. Reproduction (2009) 137 943-955