Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):385-390. doi: 10.1073/pnas.1713957115. Epub 2017 Dec 19.
Understanding how decidual CD8 T cell (CD8 dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8 dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8 dT effector responses to maintain tolerance to fetal antigens. However, CD8 dT degranulated, proliferated, and produced IFN-γ, TNF-α, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8 dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8 dT that are permissive of placental and fetal development, and reversal of this dysfunctional state, is crucial in understanding the etiology of pregnancy complications and prevention of congenital infections.
了解蜕膜 CD8 T 细胞（CD8 dT）细胞毒性的调控机制，以及这些细胞如何整合母体-胎儿耐受和抗感染免疫的竞争需求，是一个重要的研究和临床目标。效应记忆 CD8 dT 的基因表达分析显示出 T 细胞功能障碍、激活和效应功能的混合转录特征。共抑制分子 PD1、CTLA4 和 LAG3 的高蛋白表达，伴随着细胞毒性分子的低表达，表明蜕膜微环境降低了 CD8 dT 的效应反应，以维持对胎儿抗原的耐受。然而，CD8 dT 在体外刺激下脱颗粒、增殖并产生 IFN-γ、TNF-α、穿孔素和颗粒酶，表明 CD8 dT 并非永久性抑制，它们保留了对炎症事件（如感染）的反应能力。了解胎盘和胎儿发育允许的 CD8 dT 短暂功能障碍与这种功能障碍状态逆转之间的平衡，对于理解妊娠并发症的病因和预防先天性感染至关重要。
