Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy

In human pregnancy, CD14⁺ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20–30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy.     

原因不明复发性流产患者巨噬细胞表面TSP1、CD36、CD47的表达及其细胞因子的分泌

目的:探讨巨噬细胞表面分子凝血酶敏感蛋白1(TSP1)、CD36、CD47及其分泌细胞因子IL-10和IFN-γ与原因不明复发性流产发病的关系。方法:采用流式细胞技术检测10例原因不明复发性流产患者和20例正常早孕妇女外周血及蜕膜巨噬细胞表面TSP1、CD36、CD47的表达;同时用ELISPOT法检测两组外周血及蜕膜分泌IL-10和IFN-γ的巨噬细胞数。结果:原因不明复发性流产患者外周血巨噬细胞TSP1、CD36、CD47表达水平及其分泌IL-10和IFN-γ的细胞数与正常早孕妇女均无统计学差异。与正常早孕妇女比较,原因不明复发性流产患者蜕膜巨噬细胞CD36表达水平明显升高(P<0.01),TSP1表达水平明显降低(P<0.01),CD47表达水平无明显差异(P>0.05)。蜕膜组织分泌IL-10的巨噬细胞数显著降低(P<0.05),而分泌IFN-γ的巨噬细胞数量无明显差异。结论:蜕膜巨噬细胞在维持正常妊娠免疫耐受和导致原因不明复发性流产发病中起重要作用。     

Decidual leucocyte populations in early to late gestation normal human pregnancy

Most research on human decidual leucocytes to date has focused on the predominant CD56+ uterine natural killer (uNK) cell population in early pregnancy. Few reports have documented decidual leucocyte populations after 13 weeks gestation and in late pregnancy. Placental bed (decidua basalis) and non-placental bed (decidua parietalis) biopsies from normal pregnancies were taken from women undergoing termination of pregnancy in the 1st and 2nd trimesters and following Caesarean section in the 3rd trimester. Immunohistochemistry was used to quantify the numbers of decidual cells expressing CD56, CD3, CD8, CD94, NKG2A and CD14 and double labelled CD161+CD3+ NKT-like cells. Although a significant reduction in CD56+ uNK cells was found in 3rd trimester samples compared with 1st and 2nd trimester decidua, a substantial residual CD56+ leucocyte population was identified in 3rd trimester decidua. Expression of the KIR CD94/NKG2A mirrored that of CD56 at all gestational ages, providing an explanation for the absence of cytotoxic responses at the fetal–maternal interface. There was no difference in leucocyte populations between decidua basalis and decidua parietalis. Double immunohistochemical labelling revealed small numbers of decidual CD3+CD56+ and CD8+CD56+ cells, which decreased in number at term, and CD161+CD3+ cells, which increased in number at term. No differences in leucocyte populations were detected between decidua parietalis and decidua basalis. In contrast to previous reports, a substantial residual CD56+ cell population was demonstrated in 3rd trimester decidua. Decidual cytotoxic T-lymphocytes did not alter in number during gestation, while in contrast CD14+ macrophages decreased at term, representing the smallest decidual population assessed.     

妊娠早期蜕膜组织巨噬细胞分泌IL-10/IFN-γ功能的特征

目的:探讨正常妊娠早期母胎界面蜕膜组织与外周血中细胞因子分泌的格局以及单核/巨噬细胞分泌IL-10/IFN-γ的功能特征。方法:收集9例接受人工流产的正常早孕妇女外周血和蜕膜组织,用MACS法富集单核/巨噬细胞,用ELISPOT法检测细胞因子。结果:在正常妊娠早期,母胎界面蜕膜组织分泌IL-10的细胞细胞和分泌IFN-γ细胞比值显著高于外周血;蜕膜巨噬细胞分泌IL-10数量明显高于外周血单核细胞,亦明显高于蜕膜组织非巨噬细胞。结论:蜕膜组织分泌细胞因子格局的特征与外周血有差异,可能是母胎免疫耐受形成的重要途径。蜕膜巨噬细胞可通过增强IL-10的分泌调节母胎界面细胞因子格局,有利于诱导母胎免疫耐受。     

Selective distribution and pregnancy-specific expression of DC-SIGN at the maternal-fetal interface in the rhesus macaque: DC-SIGN is a putative marker of the recognition of pregnancy

We performed immunohistochemical analysis of DC-SIGN expression at the maternal-fetal interface at different stages of pregnancy in the rhesus monkey. Natural killer cells, monocytes and macrophages were observed in the nonpregnant endometrium, particularly in the luteal phase, and were increased in pregnant endometrium. No DC-SIGN+ cells were observed in the nonpregnant uterus. We observed decidual DC-SIGN+ cells within 1 week of implantation, and they increased in number during the first 5 weeks of gestation. DC-SIGN+ cells showed a clear differential distribution in the decidua in the first 2 weeks of pregnancy, being found only adjacent to the implantation site, in marked contrast to the widespread distribution of CD68+ macrophages and CD56+ NK cells throughout the endometrium. DC-SIGN+ cells also showed a more dendritic morphology than the general CD68+ cell population, and analysis of serial sections indicated an overlapping but not identical localization of these markers. Mature dendritic cells could not be detected as judged by total absence of immunostaining for CD83, CD86, DEC-205, or CD1a. DC-SIGN+ cells were defined as MHC class II+ and CD14+ by flow cytometry. We conclude that DC-SIGN expression is an early response by the primate maternal immune system to the implanting embryo. The selectively distributed population of DC-SIGN+ decidual leukocytes may represent a morphologically and phenotypically distinct subpopulation of decidual macrophages of early pregnancy that could contribute to the establishment of maternal-fetal immune tolerance.     

Invariant NKT cells increase lipopolysacchride-induced pregnancy loss by a mechanism involving Th1 and Th17 responses

Abstract

Objective: To determine the role of invariant natural killer T (iNKT) cells in infection-associated pregnancy loss.

Methods: B6 and iNKT cell-deficient Jα18^?/? mice were injected i.p. with lipopolysaccharide (LPS) or vehicle, and pregnancy outcomes were examined. Decidual iNKT cell expression of CD69 and intracellular cytokine production were analyzed. Mouse decidual iNKT cells were co-cultured with LPS or PBS-treated dendritic cells (DCs), and iNKT cell CD69 expression and intracellular and extracellular cytokine production were assessed.

Results: The embryo resorption rate was notably lessened for Jα18^?/? mice treated with LPS on day 6 or day 9 gestation in comparison with B6 mice treated with LPS. Decidual iNKT cell CD69 expression and intracellular IFN-γ and IL-17 production for B6 mice injected with LPS on day 6 or day 9 gestation were significantly up-regulated compared with PBS-treated mice. Levels of IFN-γ and IL-17 in the supernatants of the co-culture of decidual iNKT cells and LPS-sensitized DCs were strikingly increased in comparison with the co-culture of iNKT cells and PBS-treated DCs. CD69 expression and intracellular IFN-γ and IL-17 production of iNKT cells co-cultured with LPS-sensitized DCs were remarkably up-regulated compared with iNKT cells co-cultured with PBS-treated DCs.

Conclusions: Our results suggest that iNKT cells may play a role in LPS-induced pregnancy loss by Th1 and Th17 cytokine-dependent manner.     

Dynamic changes in primate endometrial leukocyte populations: differential distribution of macrophages and natural killer cells at the rhesus monkey implantation site and in early pregnancy

The distribution of uterine leukocytes during the periimplantation period cannot be readily evaluated in human pregnancy. Using immunohistochemistry we examined the distribution of macrophages, natural killer (NK) cells, and T cells in the non-pregnant endometrium and in the decidua at early stages of implantation and pregnancy in the rhesus monkey. CD68+ macrophages, CD56+ lymphocytes and CD3+ T cells were present in the proliferative and secretory endometrium. The number of macrophages and CD56+ lymphocytes dramatically increased at implantation (day 14-15 of pregnancy) and continued to be high in early pregnancy decidua. Macrophages were conspicuously more numerous in proximity to implantation site (decidua basalis) as compared to sites peripheral to the developing placenta (decidua parietalis), and were found in close association with cytotrophoblasts adjacent to the decidua, as well as around arteries invaded by extravillous cytotrophoblasts. In contrast to macrophages, CD56+ lymphocytes were more evenly distributed throughout the decidua. Few CD3+ T cells were seen in pregnancy, being scattered in the endometrial stroma with occasional aggregate formation. The distribution of uterine leukocytes vis-à-vis trophoblasts at the rhesus monkey implantation site and in early pregnancy suggests different roles for macrophages and uterine NK cells in the response to trophoblast invasion.     

孕酮和IL-15对人早孕蜕膜子宫自然杀伤(uNK)细胞促血管生成因子的调节

目的:探讨孕酮和IL-15对蜕膜子宫自然杀伤细胞(uNK)在早孕蜕膜血管生成/重塑过程中的作用。方法:免疫磁珠(MACS)分离及纯化蜕膜uNK细胞后进行体外培养,分别用不同浓度孕酮或IL-15干预72h后获取培养上清液和细胞。采用RT-PCR和ELISA检测蜕膜uNK细胞的VEGF-A、VEGF-C、Ang2的mRNA转录和蛋白表达。结果:蜕膜uNK细胞可表达多种与血管形成有关的生物活性分子,与未干预的空白对照组相比,IL-15促进uNK细胞表达VEGF-A、VEGF-C(P<0.05),且呈剂量依赖关系,但对Ang2无影响;而孕酮对uNK细胞表达上述因子均无显著影响(P>0.05)。结论:妊娠早期蜕膜uNK细胞通过表达多种促血管生成因子,在早孕蜕膜血管生成/重塑中起着重要的作用,IL-15对此有直接促进作用。     

Side population cells in the human decidua of early pregnancy exhibit stem/progenitor cell-like characteristics

It is proposed that human decidua contains a population of stem cells that are responsible for the proliferation ability during the process of embryo implantation and placenta formation and that factors in the crosstalk between the decidua and chorion may mediate decidual stem cell differentiation. This study analysed the phenotype of side population (SP) cells and investigated the clonogenicity and differentiation ability of SP cells in human decidua of early pregnancy. Serum-free culture-conditioned media of human decidua and chorion were obtained from decidua and chorion explant culture. Decidual SP cells were isolated by fluorescence-activated cell sorting. Different inducing media were added and the functional differentiation of decidual SP cells was examined. Decidual SP cells were negative for the mature decidual cell marker CD13 and prolactin and negative for CD34 and CD45 expression. Decidual SP cells formed clones after culture in colony-forming medium and they could form clones again. Differentiated cells expressing CD13 and prolactin were observed and stroma-like structures expressing CD13 were obtained. These results indicate that decidual SP cells are enriched for stem cell activity. Oestradiol, progesterone and factors in culture-conditioned media of human decidua and chorion induced their proliferation and differentiation.     

NK Cells Detect Changes in Adaptive Immunity within Mouse Decidua from Gestation Day Eight

Viable human CD56+ CD16? peripheral blood Natural Killer (NK) cells show specific in vitro binding under shear forces to ligands expressed by endothelial cells in cryostat sections of gestation day (gd)7 mouse decidua basalis. In serial assays, numbers of cells adhering to gd7 tissue are constant for men but have cyclical variation for fertile women, suggesting a brief gain in functional decidual homing potential of this NK cell subset during the menstrual cycle. Regardless of gender, numbers of adhering cells from an individual donor, increase dramatically when the substrate is decidua basalis from a later gestational timepoint. Here, we report that human blood CD56+ CD16? NK cells which adhere as single cells over gd7 decidua basalis, adhere as large clusters over gd8 and gd9 tissues, suggestive of antigen recognition and lymphocyte activation. We asked which cells within mouse decidua basalis trigger this response in CD56+ CD16? cells. Using decidua from mice transgenic for myeloid dendritic cell (mDC) expression of enhanced yellow fluorescent protein (eYFP), we found cluster formation was independent of mDC contact. Use of decidua from alymphoid mice showed clustering behavior required substrate lymphocytes. By use of decidua containing NK cells but lacking T and B cells, decidual T and/or B lymphocytes were identified as the cells altered after gd7 in a manner that activates CD56+ CD16? cell clustering. This timepoint is just prior to mouse spiral arterial modification and its detection by these indicator cells implicates adaptive, decidual immune responses in the regulation of NK cell function.     

不明原因习惯性流产患者蜕膜自然杀伤细胞活性及表型的研究

目的 :探讨原因不明习惯性流产 (UHA)患者蜕膜自然杀伤 (NK)细胞的数量、表型特征及杀伤活性 ,探讨其在UHA发病中的作用。方法 :选取确定妊娠并难免流产的UHA 32例 ,选取 2 0例正常妊娠行人工流产者作为对照组 ,用流式细胞仪检测两组蜕膜组织中NK细胞数量及表型 ,用改进的乳酸脱氢酶释放法测定NK细胞杀伤活性。结果 :正常早孕蜕膜中CD5 6+CD3- NK细胞占蜕膜单个核细胞的 60 .73± 13.2 4 % ,为蜕膜组织的优势细胞群 ,UHA患者蜕膜中CD5 6+CD3- NK细胞总量与正常妊娠蜕膜组织中相同 ,而其CD5 6+CD16- 亚群却明显低于正常妊娠组 (P <0 .0 5 ) ,CD5 6+CD16+亚群含量及CD5 6+CD16+/CD5 6+CD16- 比值均异常增高 (P均 <0 .0 5 )。UHA组蜕膜组织中NK细胞杀伤活性及其异常增高率均高于正常妊娠组 ,差异均有显著性 (P均 <0 .0 5 )。结论 :NK细胞是孕早期蜕膜组织中的优势细胞群 ,其亚群失衡及功能异常可导致自然流产     

Co-ordinate expression of Th1/Th2 phenotypes in maternal and fetal blood: evidence for a transplacental nexus

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE <300 IU/mL. Basal levels of IFN-γ, IL-4, and eotaxin in paired maternal and fetal sera were tightly correlated. Polyclonal T cell activation in vitro by Staphylococcal exotoxin B induced co-ordinate IFN-γ production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-γ. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system.     

Study on the activity and phenotype of decidual natural killer cells in patients with unexplained habitual abortions

Habitualabortionsoccurin 1to 2 %ofthechild bearingpopulation .Chromosomalaberrationistheprincipalcauseoffetallossduringtheearlystageofgestation .Oth eretiologies ,whichincludeanatomicanomalies ,endocrinedisorders,andinfections ,havealsobeendocumemtedinpatientswithhabitualabortions .Nevertheless ,in 4 0to6 0 %ofcouples ,habitualabortionsremainunexplained ,whicharecalledUHA .Recently ,theimportanceofim munologyinUHAisrecognized .Immunecellsareabun dantinhumandeciduaandarecapableofrespondingto…     

Activation antigens during the proliferative and secretory phases of endometrium and early-pregnancy decidua

BACKGROUND: Clarifying the normal distribution of activation antigens will contribute to database construction studies of monoclonal-antibody-based therapies in endometrial disorders. METHODS: In this study, endometrial tissue samples obtained during proliferative and secretory phases and decidual samples of early pregnancies were immunostained by the monoclonal antibodies anti-CD26, anti-CD30, anti-CD70, anti-CD71, and anti-CD98 using the indirect immunoperoxidase method. RESULTS: CD26 is expressed on the glandular epithelium in the endometrium and decidua. Endothelial CD26 is expressed less in the decidua when compared to the endometrium. CD30 is strongly expressed by decidual cells. It is only weakly expressed on endometrial and decidual vessels. Glandular and endothelial CD70 expression is mainly seen in the proliferative phase of the menstrual cycle. Glandular CD71 expression is less in the decidua when compared to the endometrium. Its expression on stromal cells is more in the secretory phase of the menstrual cycle and in early pregnancy deciduae. It is expressed on endometrial vessels but not on decidual vessels. Glandular CD98 is expressed more in the decidua when compared to the endometrium. This antigen exists on endometrial lymphocytes. It is strongly expressed on the endothelium in the endometrium and decidua. CONCLUSION: It seems that CD26 and CD70 are not involved in the functions of endometrial and decidual stromal cells. CD30 and CD71 are thought to be involved in decidualization. Absence of activation antigens other than CD98 on lymphocytes indicated an antigenic profile for large granular lymphocytes that is different from regular lymphocytes.     

早孕蜕膜及绒毛组织中趋化因子CXC受体3、4及其配体的表达变化和意义

目的 探讨早孕蜕膜及绒毛组织中趋化因子CXC受体(CXCR)3、4及其配体CXCL9、CXCL10和CXCL12的表达变化和意义.方法 体外分离正常早孕蜕膜组织中单个核细胞,免疫磁珠分选试剂盒纯化CD+56自然杀伤(NK)细胞,流式细胞仪分析其纯度和表型;RT-PCR技术榆测早孕蜕膜NK细胞中CXCR3和CXCR4、早孕蜕膜及绒毛组织中CXCL9、CXCL10、CXCL12的表达情况;免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法检测正常子宫内膜、早孕蜕膜组织中CXCL9和CXCL10的表达及CD+56NK细胞的分布情况,分析CXCL9、CXCL10表达量(灰度值)与CD+56NK细胞数的相关性.结果 分离纯化的早孕蜕膜NK细胞中,98.7%的细胞表型为CD56bright;早孕蜕膜NK细胞中有CXCR3和CXCR4表达;早孕蜕膜组织中有CXCL9、CXCL10表达,早孕绒毛组织中有CXCL12的表达.分泌期子宫内膜中CXC19、CXCL10表达最为56±43、59±47,较增生期子宫内膜的16±18、8±14明显升高,差异有统计学意义(P<0.05),而早孕蜕膜组织中CXCL9、CXCL10表达量为143±35、158±29,较分泌期子宫内膜进一步升高(P<0.05);分泌期子宫内膜中NK细胞数量为(60±20)个,增生期子宫内膜中NK细胞数量为(23±4)个,两者比较,差异有统计学意义(P<0.05),早孕蜕膜中NK细胞数量为(114 ±15)个,较分泌期子宫内膜进一步增多(P<0.05);子宫内膜和蜕膜组织中CXCL9、CXCL10表达量与组织中CD56+细胞数呈正相关关系(rcxL9=0.88,P<0.05;rcxcL10=0.86,P<0.05).结论 早孕蜕膜及绒毛组织中表达的CXCL9、CXCL10及CXCL12可能通过与CD56+NK细胞表面对应的趋化因子受体CXCR3、CXCR4结合而影响早孕期母-胎界面中CD56+NK细胞的聚集,从而对母-胎间免疫平衡起调控作用.     

调节性T细胞和Notch1信号通路在原因不明复发性自然流产中的作用

目的探讨调节性T细胞(Treg)和Notch1信号通路在原因不明复发性自然流产(URSA)中的作用。方法流式细胞仪检测URSA患者(URSA组)及正常妊娠妇女(对照组)蜕膜CD4~+CD25~+T细胞Treg表达比例,real time RT-PCR及Western blotting检测蜕膜中CD4~+T细胞中Notch1信号通路和叉头转录因子家族3(Foxp3)表达情况。结果 URSA组CD4~+CD25~+T细胞/淋巴细胞、CD4~+Foxp3~+T细胞/淋巴细胞和CD4~+Foxp3~+T细胞/CD4~+T细胞比例均低于对照组(P0.05)。URSA组CD4~+T细胞中Notch1-Ic、RBPJκ、Foxp3 m RNA及蛋白表达均低于对照组。结论 URSA患者蜕膜CD4~+T细胞中Notch1信号通路和Foxp3表达下调,CD4~+CD25~+T细胞表达比例下降,提示URSA患者Notch1信号通路和Foxp3表达下调可能阻碍CD4~+T细胞转化为CD4~+CD25~+T细胞,进而诱发免疫排斥,诱导流产。     

米非司酮药流时整合蛋白β3和细胞间粘附分子-1在蜕膜与绒毛内的表达

为了解米非司酮与米索前列醇对早孕流产的蜕膜、绒毛中整合蛋白 (Integrin)β3和细胞间粘附分子 1 (Intercellular adhesion molecule,ICAM 1 )的影响 ,应用流式细胞定性定量分析技术测定了 1 0例采用米非司酮与米索前列醇终止早孕妇女的蜕膜与绒毛组织中整合蛋白β3和 ICAM 1水平 ,并以 1 0例负压吸引人工流产者为对照。结果显示 :蜕膜与绒毛组织整合蛋白 β3和 ICAM 1均较对照组明显降低。实验组蜕膜组织整合蛋白 β3与 ICAM 1分别为 1 9.1± 5.0 1 %和 2 0 .6 1± 6 .51 % ,对照组分别为 2 9.3 1± 5.2 6和 2 6 .6 9± 6 .1 1 ;实验组绒毛组织整合蛋白β3与 ICAM 1分别为 2 1 .3 2± 4 .3 8%和 2 0 .2 9± 6 .4 9% ,而对照组则为 3 1 .3 1± 7.85和 2 8.6 9± 7.98。结果提示整合蛋白β3及 ICAM 1可能与维持早孕有关 ,米非司酮影响蜕膜、绒毛组织中整合蛋白 β3及 ICAM 1的表达 ,可能参与药物抗早孕机制。     

Comparison of macrophage phenotype between decidua basalis and decidua parietalis by flow cytometry

The two regions of the maternal decidua, decidua basalis and decidua parietalis, differ in the extent of trophoblast invasion and consequently in cytokines and other biological mediators, extracellular matrix and cellular components. Our aim was to compare the phenotypic features of macrophages from the two decidual regions across a broad gestational age range. We isolated macrophages by enzymatic digestion from healthy decidua samples obtained after elective abortions, at 9-18-week and at 19-23-weeks, or after term deliveries (caesarean sections at term and spontaneous term vaginal deliveries). Macrophages were analysed by flow cytometry applying the same instrument settings to all the samples to allow semi-quantitative comparison of the expression of a particular marker between different samples. We found higher expressions of CD80, CD86 and HLA-DR, suggestive of a more activated phenotype of decidual macrophages, at early/mid pregnancy than at term. Marginal differences were found between term decidual macrophages obtained after spontaneous vaginal deliveries or caesarean sections which imply that the parturient process is not associated with decidual macrophage activation. The expressions of CD105, DC-SIGN and MMR were the strongest in decidua basalis of mid pregnancy and indicate the importance of decidual macrophages in tissue homeostasis at the uteroplacental interface.     

早孕蜕膜组织淋巴细胞在妊娠中的作用

目的 探讨子宫内膜局部免疫细胞在妊娠中的作用,方法 采用免疫组化技术和原位杂交技术,研究２０例正常孕妇的早孕蜕膜组织内淋巴细胞的分布,表型特征及穿孔素蛋白和ｍＲＮＡ的表达。结果 早孕蜕膜组织内Ｔ总淋巴细胞（ＣＤ３淋巴细胞）抑制或杀伤了Ｔ淋巴细胞（ＣＤ８淋巴细胞）较少,约占３％,辅助Ｔ淋巴细胞（ＣＤ４淋巴细胞）极少,甚至看不到,早孕蜕膜组织内大部分淋巴细胞为表达穿孔素的自然杀伤样细胞ＣＤ（５６非典型