University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria.
Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
Front Immunol. 2020 Sep 11;11:582065. doi: 10.3389/fimmu.2020.582065. eCollection 2020.
The phenotype and function of immune cells that reside at the maternal-fetal interface in humans and mice have been, and still are, extensively studied with the aim to fully comprehend the complex immunology of pregnancy. In pigs, information regarding immune cell phenotypes is limited and mainly focused on early gestation whereas late gestation has not yet been investigated. We designed a unique methodology tailored to the porcine epitheliochorial placenta, which allowed us to address immune phenotypes separately in the maternal endometrium (ME) and fetal placenta (FP) by flow cytometry. In-depth phenotyping of NK cells, non-conventional and conventional T cells within maternal blood (mBld), ME, FP, and fetal spleen (fSpln) revealed major differences between these anatomic sites. In both maternal compartments, all NK cells were perforin and had NKp46-defined phenotypes indicative of late-stage differentiation. Likewise, T cells with a highly differentiated phenotype including CD2CD8αCD27perforin γδ T cells, CD27perforin cytolytic T cells (CTLs), and T-bet CD4CD8αCD27 effector memory T (Tem) cells prevailed within these compartments. The presence of highly differentiated T cells was also reflected in the number of cells that had the capacity to produce IFN-γ. In the FP, we found NK cells and T cell populations with a naive phenotype including CD2CD8αCD27perforin γδ T cells, T-betCD4CD8αCD27 T cells, and CD27perforin CTLs. However, also non-naive T cell phenotypes including CD2CD8αCD27perforin γδ T cells, T-betCD4CD8αCD27 Tem cells, and a substantial proportion of CD27perforin CTLs resided within this anatomic site. Currently, the origin or the cues that steer the differentiation of these putative effector cells are unclear. In the fSpln, NKp46 NK cells and T cells with a naive phenotype prevailed. This study demonstrated that antigen-experienced immune cell phenotypes reside at the maternal-fetal interface, including the FP. Our methodology and our findings open avenues to study NK and T cell function over the course of gestation. In addition, this study lays a foundation to explore the interplay between immune cells and pathogens affecting swine reproduction.
人类和小鼠母体-胎儿界面上免疫细胞的表型和功能已经并仍在广泛研究，目的是充分理解妊娠的复杂免疫学。在猪中，关于免疫细胞表型的信息有限，主要集中在早期妊娠，而晚期妊娠尚未得到研究。我们设计了一种独特的方法，专门针对猪的上皮绒毛胎盘，通过流式细胞术可以分别在母体子宫内膜（ME）和胎儿胎盘（FP）中解决免疫表型问题。对母体血液（mBld）、ME、FP 和胎儿脾脏（fSpln）中的 NK 细胞、非常规和常规 T 细胞进行深入表型分析，揭示了这些解剖部位之间的主要差异。在母体的两个部位，所有的 NK 细胞都是穿孔素阳性，具有 NKp46 定义的晚期分化表型。同样，具有高度分化表型的 T 细胞，包括 CD2CD8αCD27 穿孔素 γδ T 细胞、CD27 穿孔素细胞毒性 T 细胞（CTL）和 T 细胞因子 T-bet CD4CD8αCD27 效应记忆 T（Tem）细胞，在这些部位也占主导地位。高分化 T 细胞的存在也反映在具有产生 IFN-γ 能力的细胞数量上。在 FP 中，我们发现 NK 细胞和 T 细胞群体具有幼稚表型，包括 CD2CD8αCD27 穿孔素 γδ T 细胞、T 细胞因子 T-bet CD4CD8αCD27 T 细胞和 CD27 穿孔素 CTL。然而，也有非幼稚 T 细胞表型，包括 CD2CD8αCD27 穿孔素 γδ T 细胞、T 细胞因子 T-bet CD4CD8αCD27 Tem 细胞和相当比例的 CD27 穿孔素 CTL，存在于这个解剖部位。目前，这些潜在效应细胞分化的起源或线索尚不清楚。在 fSpln 中，NKp46 NK 细胞和具有幼稚表型的 T 细胞占主导地位。本研究表明，抗原经验免疫细胞表型存在于母体-胎儿界面，包括 FP。我们的方法和发现为研究妊娠过程中 NK 和 T 细胞的功能开辟了途径。此外，这项研究为探索影响猪繁殖的免疫细胞与病原体之间的相互作用奠定了基础。
