The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a Listeria monocytogenes infection
The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a Listeria monocytogenes infection
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DOI：
10.4049/jimmunol.171.1.37
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发表时间：
2003-07-01
影响因子：
4.4
通讯作者：
Pollard, JW
中科院分区：
文献类型：
--
作者：
Barber, EM;Pollard, JW
在小鼠怀孕期间，子宫自然杀伤（uNK）细胞大量积聚在胎盘的子宫内膜侧。在这项研究中，我们表明成熟和未成熟的 uNK 细胞的存在都需要 IL-15。由于重组激活基因 (Rag) 2/共同细胞因子受体伽玛链 (Rag2(-/-) gamma(c)(-/-)) 基因无效突变而对 NK 细胞阴性小鼠进行骨髓移植，表明 uNK 细胞起源于骨髓，需要 IL-15 才能发育。 NK 细胞被认为是对细胞内病原体（例如单核细胞增生李斯特菌）免疫反应的核心参与者，这种细菌也倾向于在胎盘中复制。然而，与野生型小鼠相比，IL-15(-/-)、NK细胞缺陷小鼠相对免受这种感染，并且在怀孕期间，NK细胞的缺失不会损害该部位的免疫反应。 uNK细胞的丧失导致蜕膜异常，包括动脉壁增厚、管腔变窄和基底蜕膜细胞减少。这些缺陷通过 Rag2(-/-) gamma(c)(-/-) 小鼠的骨髓移植得到修复，恢复了 uNK 细胞群。然而，IL-15(-/-)小鼠的蜕膜异常不会导致不孕，因为妊娠时间和产仔数与野生型小鼠相当。胎儿体重轻度受损，与动脉病理学一致。这些结果表明，成功怀孕不需要 uNK 细胞，并且无论是怀孕小鼠还是非怀孕小鼠，NK 细胞对于单核细胞增生利斯特氏菌的充分免疫反应都不是必需的。
During pregnancy in mice, uterine natural killer (uNK) cells abundantly accumulate on the mesometrial side of the placenta. In this study, we show that the presence of both mature and immature uNK cells requires IL-15. Bone marrow transplantation of NK cell-negative mice due to null mutations in the recombination-activating gene (Rag) 2/common cytokine receptor gamma-chain (Rag2(-/-) gamma(c)(-/-)) genes indicated that uNK cells originate from the bone marrow and require IL-15 to develop. NK cells are thought to be central players in the immune response to intracellular pathogens such as Listeria monocytogenes, a bacterium that also has a predilection for replication in the placenta. However, IL-15(-/-), NK cell-deficient mice were relatively protected from this, infection compared with wild-type mice, and during pregnancy the absence of NK cells did not compromise the immune response at this site. The loss of uNK cells results in decidual abnormalities, including thickening of the arterial walls with luminal narrowing and a hypocellular decidua basalis. These defects were rescued by bone marrow transplantation of the Rag2(-/-) gamma(c)(-/-) mice that restored the uNK cell population. The decidual abnormalities in the IL-15(-/-) mice however did not result in infertility as gestation times and litter sizes were comparable to those of ' wild-type mice. Fetal weights were mildly compromised, consistent with the arterial pathologies. These results show that uNK cells are not required for successful pregnancy and that NK cells are not essential for an adequate immune response to L. monocytogenes in either pregnant or nonpregnant mice.