Transplantation into genetically alymphoid mice as an approach to dissect the roles of uterine natural killer cells during pregnancy - A review

Transplantation into genetically alymphoid mice as an approach to dissect the roles of uterine natural killer cells during pregnancy - A review
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DOI:
10.1053/plac.1999.0518
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发表时间:
2000-03-01
期刊:
影响因子:
3.8
通讯作者:
Ashkar, AAA
Ashkar, AAA
中科院分区:
医学3区
文献类型:
--
作者:
Croy, BA;Di Santo, JP;Ashkar, AAA

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自然杀伤(NK)细胞系遗传缺陷的小鼠缺乏子宫(Unk细胞),并在其植入部位表现出形态计量可量化的组织病理学。两个特殊的小鼠品系,Tg epsilon,26和RAG-2 Null x Gamma c Null,已经成功地用作移植受体,以解决与Unk细胞生物学有关的问题。Unk细胞在来自正常小鼠的蜕膜化子宫移植段内不分化,这些子宫移植段原位吻合到免疫缺陷宿主中。Unk细胞确实出现在植入具有免疫活性的宿主体内的类似移植物中,这表明Unk细胞或其祖细胞一定是在子宫中。这一点通过将脾细胞移植到怀孕的Unk细胞缺陷受体中得到证实。只有怀孕捐赠者的脾细胞,而不是非怀孕捐赠者的脾细胞,才会回到子宫。体内实验中的归巢不依赖于CC趋化因子受体CCR-2和CCR-5。新生或成年Unk细胞缺陷小鼠的长期骨髓细胞重建已证实Unk细胞在干扰素-γ介导的蜕膜小动脉调节中发挥功能作用。通过利用突变和基因去除的小鼠作为供体,将组织或造血细胞移植到Unk细胞缺陷小鼠,应该可以充分表征这些妊娠特异性子宫淋巴细胞的体内调节和功能。(C)2000年IFPA和哈考特出版有限公司。
Mice genetically deficient in the natural killer (NK) cell lineage lack uterine (uNK cells) and demonstrate morphometrically-quantifiable histopathology within their implantation sites. Two particular mouse strains, tg epsilon,26 and RAG-2 null x gamma c null, have been used successfully as transplant recipients to address questions relating to the biology of uNK cells. uNK cells did not differentiate within decidualized uterine graft segments from normal mice, which were anastomosed orthotopically into immunodeficient hosts. uNK cells did appear in similar grafts placed into immunocompetent hosts, indicating that uNK cells or their progenitors must home to the uterus. This was confirmed by splenocyte transplantation into pregnant uNK cell deficient recipients. Only splenocytes from pregnant donors, not those from non-pregnant donors, homed to the uterus. Homing in this in vivo assay was independent of the CC-chemokine receptors, CCR-2 and CCR-5. Longer-term bone marrow cell reconstitution of neonatal or virgin adult uNK cell-deficient mice has identified a functional role for uNK cells in modification of the decidual arterioles which is mediated by IFN-gamma. By utilizing mutant and gene-ablated mice as donors for tissue or haematopoietic cell transplants to uNK cell deficient mice, it should be possible to fully characterize the in vivo regulation and functions of these pregnancy-specific uterine lymphocytes. (C) 2000 IFPA and Harcourt Publishers Ltd.