Lea R G, Flanders K C, Harley C B, Manuel J, Banwatt D, Clark D A
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
J Immunol. 1992 Feb 1;148(3):778-87.
Postimplantation murine decidual tissue from allopregnant C3H mice has been shown to release in vitro a potent immunosuppressive factor closely related to transforming growth factor (TGF)-beta 2 but slightly lower in apparent molecular weight. Decidual suppressor factor (DSF) activity was first detected in decidual tissue supernatant at day 9.5 of gestation and reached a plateau by day 10.5 to 12.5. By Northern analysis of decidual and placental tissue with a simian TGF-beta 2 probe, two characteristic TGF-beta 2 mRNA transcripts were detected in decidual tissue. In situ hybridization analysis of C3H implant sites, with the simian (pGEM-G1G2) TGF-beta 2 riboprobe, revealed a small population of TGF-beta 2+ cells localized to postimplantation decidua basalis and metrial gland cell area after day 8.5. On and before day 8.5, when DSF was not detectable, few TGF-beta 2 mRNA+ cells were detected. To test for TGF-beta release in situ, sections of uterine tissue were stained with antibody specific for TGF-beta 2, that identified DSF in Western blots. In postimplantation tissues (day 9.5, 12.5) patchy anti-TGF-beta 2 staining was seen over decidual tissue. Before day 9.5, slight and diffuse staining over decidual tissue was present with more marked staining of extradecidual tissue. Very little staining was noted over day 9.5 decidual tissue by using anti-TGF-beta 1 antibody as a control; however, some staining was seen over postimplantation fetal trophoblast and myometrial tissue. Fractionation of disaggregated postimplantation decidua by velocity sedimentation revealed that TGF-beta 2 mRNA+ cells were predominantly small and sedimented in the same fraction(s) as those cells previously shown to release DSF in vitro. Thus, the release of TGF-beta 2 related DSF correlates with the in situ detection of TGF-beta 2 mRNA and the in situ release of TGF-beta 2 peptide. These studies suggest that DSF may be a form of TGF-beta 2 released by a population of small lymphocytic decidual suppressor cells.
已证明,同种异体妊娠C3H小鼠植入后蜕膜组织在体外可释放一种强效免疫抑制因子,该因子与转化生长因子(TGF)-β2密切相关,但表观分子量略低。蜕膜抑制因子(DSF)活性最早在妊娠第9.5天在蜕膜组织上清液中检测到,并在第10.5天至12.5天达到平台期。用猴TGF-β2探针对蜕膜和胎盘组织进行Northern分析,在蜕膜组织中检测到两种特征性的TGF-β2 mRNA转录本。用猴(pGEM-G1G2)TGF-β2核糖探针对C3H植入部位进行原位杂交分析,发现在第8.5天后,一小群TGF-β2+细胞定位于植入后基蜕膜和子宫肌腺细胞区域。在第8.5天及之前,当无法检测到DSF时,几乎检测不到TGF-β2 mRNA+细胞。为了检测原位TGF-β的释放,用对TGF-β2特异的抗体对子宫组织切片进行染色,该抗体在Western印迹中可识别DSF。在植入后组织(第9.5天、12.5天)中,在蜕膜组织上可见散在的抗TGF-β2染色。在第9.5天之前,蜕膜组织上有轻微弥漫性染色,蜕膜外组织染色更明显。以抗TGF-β1抗体作为对照,在第9.5天的蜕膜组织上几乎没有观察到染色;然而,在植入后的胎儿滋养层和子宫肌层组织上可见一些染色。通过速度沉降对植入后蜕膜进行分级分离,发现TGF-β2 mRNA+细胞主要为小细胞,沉降在与先前显示在体外释放DSF的细胞相同的级分中。因此,TGF-β2相关DSF的释放与TGF-β2 mRNA的原位检测以及TGF-β2肽的原位释放相关。这些研究表明,DSF可能是一小群淋巴细胞性蜕膜抑制细胞释放的TGF-β2的一种形式。