免疫治疗对母胎交界面NK细胞表面CD69表达水平的影响及其与鼠胚和鼠仔预后的关系(英文)

Effects of immunotherapy on CD69 expression on NK cells at the fetomaternal interface and the relationship with the outcomes of murine fetuses and pups

目的 :研究反复自然流产 (recurrentspontaneousabortion ,RSA)模型CBA/J×DBA/ 2小鼠母胎交界面NK细胞表面CD69分子的表达水平 ,并评价淋巴细胞免疫治疗 (lymphocyteimmunotherapy,LIT)对CD69表达水平的影响及其与鼠胚和鼠仔预后的关系。方法 :评价CBA/J×DBA/ 2、C57BL/ 6×DBA/ 2和BALB/c×DBA/ 2小鼠胚胎和鼠仔的预后 ,绘制出生后 1 - 2 1d鼠仔离乳前生长曲线和Kaplan -Meier生存分析曲线。并且采用PE -CD69和FITC -DX5双色流式细胞术检测在有或无LIT的情况下 ,母胎交界面NK细胞表面CD69分子的表达水平。此外 ,对CD1 6/CD32 +NK细胞亚群等也进行检测。结果 :在孕期母鼠体重平均增长幅度、平均每窝产仔数、新生鼠仔出生第 1d平均体重和胚胎吸收率等方面 ,CBA/J×DBA/ 2小鼠与生殖力正常的对照组相比均有显著差异。在CBA/J×DBA/ 2小鼠中 ,代表活化型NK细胞的CD69+ DX5+ 细胞比率也显著高于对照组。而有效的LIT能够显著降低CD69在母胎交界面NK细胞表面的表达水平 ,并相应地显著降低胚胎吸收率。结论 :CD69+ DX5+ 细胞在胚胎被排斥的机制中可能具有重要作用。

AIM: To examine the expression of CD69 on NK cells at the fetomaternal interface in CBA/J×DBA/2 mice as a model of recurrent spontaneous abortion (RSA), and to evaluate the effects of lymphocyte immunotherapy (LIT) on the level of CD69 expression and the relationship with the outcomes of murine fetuses and pups. METHODS: The outcomes of murine fetuses and pups were evaluated in breeding pairs of CBA/J×DBA/2, C57BL/6×DBA/2 and BALB/c×DBA/2 mice. Both preweaning growth curves and Kaplan-Meier survival graphs of pups were constructed throughout postnatal days 1 to 21. In addition, the level of CD69 expression on NK cells at the fetomaternal interface with and without LIT were determined by two-color flow cytometric analysis, stained with PE-CD69 and FITC-DX5. The subpopulation of CD16/CD32 + NK cells was also evaluated. RESULTS: Statistically significant differences were observed between CBA/J×DBA/2 mice and normal fertile controls in the median increase of maternal weight during pregnancy, the number of pups born per litter, the median neonatal weight on postnatal day 1, and the resorption rate of fetuses. The proportion of CD69 +DX5 + cells which represents activated NK cells was significantly higher in CBA/J×DBA/2 mice compared with normal fertile controls, while efficient LIT was able to dramatically decrease the expression of CD69 on NK cells at the fetomaternal interface and this was associated with the decrease of resorption rate accordingly. CONCLUSION: The fraction of CD69 +DX5 + cells seems to be functionally important in the mechanisms by which the embryos were rejected, whereas efficient LIT is capable of reducing the abortion rate via decreasing the expression of CD69 molecules on NK cells at the fetomaternal interface.