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

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• 作者：Yi Lin ; Yanmin Zhong ; Shigeru Saito ; Yijing Chen ; Weizai Shen ; Jingfang Di ; Shan Zeng
• 关键词：Immature NK cell ; reproductive immunology ; tolerance ; Toll-like receptor
• 刊名：Fertility and Sterility
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：91
• 期：6
• 页码：2676-2686
• 全文大小：443 K

文摘

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) agonists.

Main Outcome Measure(s)

Flow cytometric analysis was performed to detect the percentage of cell subsets, and standard ⁵¹Cr 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-tetraosylceramide⁺, CD25⁺, CD122⁺, Thy-1 (CD90)^hi, c-kit (CD117)^hi, and interleukin-10⁺. In addition, the percentage of interferon-γ⁺ 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-γ⁺ 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 ⁵¹Cr 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.