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早期小鼠蜕膜基底的子宫自然杀伤细胞伙伴关系。

Uterine natural killer cell partnerships in early mouse decidua basalis.

机构信息

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

出版信息

J Leukoc Biol. 2016 Oct;100(4):645-655. doi: 10.1189/jlb.1HI0515-226R. Epub 2016 Mar 21.

Abstract

The decidua basalis of developing mouse implantation sites is highly enriched in CD45 leukocytes. In intact, syngeneically mated C57BL/6 decidua basalis examined at gestation day 8.5 by whole-mount in situ immunohistochemistry, leukocyte, but not trophoblast, conjugations were reported. Nothing is known regarding time course, frequency, composition, or importance of physiologic decidual CD45 cell pairing. In this study, we confirmed the presence of anti-CD54/anti-CD11a immune synapses in CD45 decidual cell conjugates and characterized their cellular heterogeneity. Conjugated cell pairs were virtually absent before implantation (virgin and gestation days 3.5 and 4.5), were infrequent at gestation day 5.5, but involved 19% of all CD45 cells by gestation day 8.5, then declined. By gestation day 8.5, almost all CD45 cells coexpressed CD31, and 2 CD45CD31 cells composed most conjugates. Conjugation partners were defined for 2 nonoverlapping uterine natural killer cell subsets (Ly49C/I /Dolichos biflorus agglutinin lectin and Ly49C/I/Dolichos biflorus agglutinin lectin). Ly49C/I uterine natural killer cells were the major subset from before mating up to gestation day 6.5. At gestation day 5.5/6.5, uterine natural killer cell conjugates involving Ly49C/I cells were more abundant. By gestation day 8.5/9.5, Dolichos biflorus agglutinin lectin uterine natural killer cells were the dominant subset with Dolichos biflorus agglutinin lectin/Dolichos biflorus agglutinin lectin homologous conjugates and Dolichos biflorus agglutinin lectin/Dolichos biflorus agglutinin lectin heterologous conjugates dominating uterine natural killer cell pairings. At gestation day 6.5, both Ly49C/I/CD45 and Dolichos biflorus agglutinin lectin/CD45 heterologous conjugate pairs strongly engaged antigen-presenting cells (CD11c, CD68, or major histocompatibility complex class II). By gestation day 8.5, dominant partners of Ly49C/I/CD45 and Dolichos biflorus agglutinin lectin/CD45 heterologous conjugates are T cells (CD8 >CD4). Heterologous conjugates that did not involve uterine natural killer cells occurred but did not suggest antigen presentation to T cells. These data identify gestation day 6.5-8.5 in the pregnant mouse as a critical window for leukocyte interactions that may establish immune regulation within implantation sites.

摘要

处于发育中的小鼠着床部位的蜕膜基底层富含 CD45 白细胞。在妊娠第 8.5 天通过整体原位免疫组织化学检查同基因交配的 C57BL/6 蜕膜基底层时,报告了白细胞,但不是滋养层的连接。关于生理蜕膜 CD45 细胞配对的时间过程、频率、组成或重要性,目前尚不清楚。在这项研究中,我们证实了 CD45 蜕膜细胞偶联物中存在抗 CD54/抗 CD11a 免疫突触,并对其细胞异质性进行了表征。在妊娠第 3.5 天、第 4.5 天和第 5.5 天之前,偶联细胞对几乎不存在,在妊娠第 5.5 天很少见,但在妊娠第 8.5 天占所有 CD45 细胞的 19%,然后下降。到妊娠第 8.5 天,几乎所有的 CD45 细胞都表达 CD31,并且 2 个 CD45CD31 细胞组成了大多数偶联物。对于 2 个非重叠的子宫自然杀伤细胞亚群(Ly49C/I /多花胡枝子凝集素和 Ly49C/I /多花胡枝子凝集素),定义了偶联物的配体。在交配前到妊娠第 6.5 天,Ly49C/I 子宫自然杀伤细胞是主要亚群。在妊娠第 5.5/6.5 天,涉及 Ly49C/I 细胞的子宫自然杀伤细胞偶联物更为丰富。到妊娠第 8.5/9.5 天,多花胡枝子凝集素子宫自然杀伤细胞是优势亚群,具有多花胡枝子凝集素/多花胡枝子凝集素同源偶联物和多花胡枝子凝集素/多花胡枝子凝集素异源偶联物主导着子宫自然杀伤细胞的配对。在妊娠第 6.5 天,Ly49C/I/CD45 和多花胡枝子凝集素/CD45 异源偶联对均强烈参与抗原呈递细胞(CD11c、CD68 或主要组织相容性复合体 II)。到妊娠第 8.5 天,Ly49C/I/CD45 和多花胡枝子凝集素/CD45 异源偶联的优势配体是 T 细胞(CD8 > CD4)。但发生了不涉及子宫自然杀伤细胞的异源偶联物,但这并不意味着向 T 细胞呈递抗原。这些数据确定了妊娠第 6.5-8.5 天的小鼠怀孕期为白细胞相互作用的关键窗口,可能在着床部位建立免疫调节。

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