Characterization of natural killer cells in nonobese diabetic/severely compromised immunodeficient mice during pregnancy

Objective: To characterize uterine natural killer (uNK) cells in nonobese diabetic/severely compromised immunodeficient (NOD/SCID) mice and investigate the potential role of these cells in pregnancy tolerance. Design: An animal model-based study. Setting: Academic research center in a university. Animal(s): Syngeneic pregnant NOD/SCID mice were compared with non-immunodeficient BALB/c mice. Intervention(s): Induction of Toll-like receptor (TLR) agoinsts. Main Outcome Measure(s): Flow cytometric analysis was performed to detect the percentage of cell subsets, and standard Cr-51 release assay was performed to determine cytotoxicity. Result(s): The dominant subset of uNK cells in NOD/SCID mice is DX5 (CD49b)(+), asialo ganglio-N-tetraosyleeramide(+), CD25(+), CD122(+), Thy-1 (CD90)(hi), c-kit (CD117)(hi), and interleukin-10(+). In addition, the percentage of interferon-gamma(+) subset was slightly increased in response to selected TLR agonists in the NOD/SCID mice, whereas the corresponding percentage in BALB/c mice could be increased dramatically. Such an effect could be abrogated by inhibitors, including LY294002, SP600125, and PD98059. The significant increase of interferon-gamma(+) NK cell percentage in BALB/c mice was concomitant with the increase of the embryo resorption rate. In contrast, the resorption rate in NOD/SCID mice was not significantly increased upon the induction of polyinosinic polycytidylic acid or lipopolysaccharide. As expected, the NK cells from NOD/SCID mice display a detectable but lower cytotoxicity than BALB/c, as determined by standard Cr-51 release assay. In addition, the uNK cells from NOD/SCID mice also display a hyposensitivity to lipopolysaccharide-induced production of inducible nitric oxide synthase. Conclusion(s): A considerable percentage of immature NK cells were detected at the fetomaternal interface in NOD/SCID mice. These cells were hyposensitive to the stimulation of selected TLR agonists. Such a status seemed to be beneficial for the maintenance of pregnancy. (Fertil Steril (R) 2009;91:2676-86. (C)2009 by American Society for Reproductive Medicine.)