Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Front Immunol. 2019 Apr 2;10:625. doi: 10.3389/fimmu.2019.00625. eCollection 2019.
Adaptations of the maternal immune response are necessary for pregnancy success. Insufficient immune adaption is associated with pregnancy pathologies such as infertility, recurrent miscarriage, fetal growth restriction, spontaneous preterm birth, and preeclampsia. The maternal immune system is continuously exposed to paternal-fetal antigens; through semen exposure from before pregnancy, through fetal cell exposure in pregnancy, and through microchimerism after pregnancy. This results in the generation of paternal-fetal antigen specific memory T cells. Memory T cells have the ability to remember previously encountered antigens to elicit a quicker, more substantial and focused immune response upon antigen reencounter. Such fetal antigen specific memory T cells could be unfavorable in pregnancy as they could potentially drive fetal rejection. However, knowledge on memory T cells in pregnancy has shown that these cells might play a favorable role in fetal-maternal tolerance rather than rejection of the fetus. In recent years, various aspects of immunologic memory in pregnancy have been elucidated and the relevance and working mechanisms of paternal-fetal antigen specific memory T cells in pregnancy have been evaluated. The data indicate that a delicate balance of memory T cells seems necessary for reproductive success and that immunologic memory in reproduction might not be harmful for pregnancy. This review provides an overview of the different memory T cell subtypes and their function in the physiology and in complications of pregnancy. Current findings in the field and possible therapeutic targets are discussed. The findings of our review raise new research questions for further studies regarding the role of memory T cells in immune-associated pregnancy complications. These studies are needed for the identification of possible targets related to memory mechanisms for studies on preventive therapies.
母体免疫反应的适应对于妊娠的成功是必要的。免疫适应不足与不孕、反复流产、胎儿生长受限、自发性早产和子痫前期等妊娠病理有关。母体免疫系统不断受到父胎抗原的暴露；通过妊娠前的精液暴露、妊娠期间的胎儿细胞暴露以及妊娠后的微嵌合现象。这导致了父胎抗原特异性记忆 T 细胞的产生。记忆 T 细胞具有记住以前遇到过的抗原的能力，以便在抗原再次遇到时引发更快、更实质性和更集中的免疫反应。这些针对胎儿抗原的特异性记忆 T 细胞在妊娠中可能是不利的，因为它们可能潜在地导致胎儿排斥。然而，关于妊娠中记忆 T 细胞的知识表明，这些细胞可能在胎儿-母体耐受中发挥有利作用，而不是排斥胎儿。近年来，妊娠中免疫记忆的各个方面已经得到阐明，并且评估了父胎抗原特异性记忆 T 细胞在妊娠中的相关性和作用机制。数据表明，记忆 T 细胞的微妙平衡似乎对于生殖成功是必要的，并且生殖中的免疫记忆可能对妊娠无害。这篇综述提供了不同记忆 T 细胞亚群及其在妊娠生理和并发症中的功能的概述。讨论了该领域的当前发现和可能的治疗靶点。我们的综述结果提出了关于记忆 T 细胞在与免疫相关的妊娠并发症中的作用的进一步研究的新问题。这些研究对于确定与记忆机制相关的可能靶点以进行预防治疗的研究是必要的。
