Engraftment of bone marrow from severe combined immunodeficient (SCID) mice reverses the reproductive deficits in natural killer cell-deficient tg epsilon 26 mice.
Engraftment of bone marrow from severe combined immunodeficient (SCID) mice reverses the reproductive deficits in natural killer cell-deficient tg epsilon 26 mice.
复制标题
DOI：
10.1084/jem.187.2.217
复制
发表时间：
1998-01-19
期刊：
影响因子：
--
通讯作者：
Croy BA
中科院分区：
文献类型：
--
作者：
Guimond MJ;Wang B;Croy BA
在妊娠期间，小鼠子宫系膜三角区出现大量短暂的自然杀伤（NK）细胞。最近使用基因消融和转基因小鼠实现的子宫（u）NK细胞的耗尽导致病理学。纯合子NK和T细胞缺陷型tgε26小鼠交配后妊娠，正常uNK细胞频率<1%，未发育着床部位相关子宫腺，以及水肿性蜕膜伴血管病理，包括异常高的血管壁/管腔比。64%的胎儿丢失发生在妊娠中期，胎盘较小。这些特征在妊娠T细胞缺陷小鼠中均未观察到。为了证实NK细胞缺陷在这些生殖缺陷中的作用，使用来自B和T细胞缺陷scid/scid供体的骨髓对tgε26雌性进行移植。移植的妊娠雌性在研究的所有妊娠日（第10、12和14天）具有uNK细胞群体的恢复、诱导的子宫腺分化、减少的蜕膜和蜕膜血管中的异常、增加的胎盘尺寸和胎儿活力的恢复。因此，uNK细胞似乎在妊娠中具有促进蜕膜健康、着床部位适当血管化和胎盘大小的关键功能。
A large, transient population of natural killer (NK) cells appears in the murine uterine mesometrial triangle during pregnancy. Depletion of uterine (u) NK cells, recently achieved using gene-ablated and transgenic mice, results in pathology. Pregnancies from matings of homozygous NK and T cell–deficient tgε26 mice have <1% of normal uNK cell frequency, no development of an implantation site–associated metrial gland, and an edematous decidua with vascular pathology that includes abnormally high vessel walls/lumens ratios. Fetal loss of 64% occurs midgestation and placentae are small. None of these features are seen in pregnant T cell–deficient mice. To confirm the role of the NK cell deficiency in these reproductive deficits, transplantation of tgε26 females was undertaken using bone marrow from B and T cell–deficient scid/scid donors. Engrafted pregnant females have restoration of the uNK cell population, induced metrial gland differentiation, reduced anomalies in the decidua and decidual blood vessels, increased placental sizes, and restoration of fetal viability at all gestational days studied (days 10, 12, and 14). Thus, uNK cells appear to have critical functions in pregnancy that promote decidual health, the appropriate vascularization of implantation sites, and placental size.