The Role of CD4+CD25bright Regulatory T Cells in the Maintenance of Pregnancy, Premature Rupture of Membranes, and Labor

Seol, Hyun Joo; Oh, Min Jeong; Lim, Ji Eun; Jung, Nan Hee; Yoon, Soo Young; Kim, Hai Joong

doi:10.3349/ymj.2008.49.3.366

Cited by 18 publications

(24 citation statements)

References 18 publications

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“…Tregs significantly decline at term, probably in response to the onset of labor. This agrees with the recent observations of changes in Treg functions in preterm labor deliveries (Seol et al , 2008; Xiong et al , 2010; Schober et al , 2012). …”

Section: Uterine Nk Cells and Tregs In Pregnancy: Why Are They There supporting

confidence: 93%

Natural killer cells and regulatory T cells in early pregnancy loss

Sharma¹

2014

Int. J. Dev. Biol.

124

107

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Survival of the allogeneic embryo in the uterus depends on the maintenance of immune tolerance at the maternal-fetal interface. The pregnant uterus is replete with activated maternal immune cells. How this immune tolerance is acquired and maintained has been a topic of intense investigation. The key immune cells that predominantly populate the pregnant uterus are natural killer (NK) cells. In normal pregnancy, these cells are not killers, but rather provide a microenvironment that is pregnancy compatible and supports healthy placentation. In placental mammals, an array of highly orchestrated immune elements to support successful pregnancy outcome has been incorporated. This includes active cooperation between maternal immune cells, particularly NK cells, and trophoblast cells. This intricate process is required for placentation, immune regulation and to remodel the blood supply to the fetus. During the past decade, various types of maternal immune cells have been thought to be involved in cross-talk with trophoblasts and in programming immune tolerance. RegulatoryT cells (Tregs) have attracted a great deal of attention in promoting implantation and immune tolerance beyond implantation. However, what has not been fully addressed is how this immune-trophoblast axis breaks down during adverse pregnancy outcomes, particularly early pregnancy loss, and in response to unscheduled inflammation. Intense research efforts have begun to shed light on the roles of NK cells and Tregs in early pregnancy loss, although much remains to be unraveled in order to fully characterize the mechanisms underlying their detrimental activity. An increased understanding of host-environment interactions that lead to the cytotoxic phenotype of these otherwise pregnancy compatible maternal immune cells is important for prediction, prevention and treatment of pregnancy maladies, particularly recurrent pregnancy loss. In this review, we discuss relevant information from experimental and human models that may explain the pregnancy disrupting roles of these pivotal sentinel cells at the maternal-fetal interface.

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Section: Uterine Nk Cells and Tregs In Pregnancy: Why Are They There supporting

confidence: 93%

Natural killer cells and regulatory T cells in early pregnancy loss

Sharma¹

2014

Int. J. Dev. Biol.

124

107

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“…98,99 It has been observed that immunotherapy of women with URPL using paternal mononuclear cells could cause reduction and increase, respectively, in levels of Th17 and Treg cells. LIT induces production of anti-paternal cytotoxic antibodies (APCAs), mixed lymphocyte reaction blocking antibodies (MLR-Babs or MLR-BF), and anti-idiotypic antibodies (Ab2) that can cover paternal human leukocyte antigen (HLA) in the surface of the fetus and thereby prevent from maternal natural killer (NK) and T cells attacking.…”

Section: Lit For Patients With Rplmentioning

confidence: 99%

“…The CD4+CD25+ Treg cells levels in peripheral blood lymphocytes of women suffering from URPL are lower than non-pregnant healthy women, which implies possible contribution of these cells in tolerance of maternal immune to conceptus antigens and thus conservation of pregnancy. 98,99 It has been observed that immunotherapy of women with URPL using paternal mononuclear cells could cause reduction and increase, respectively, in levels of Th17 and Treg cells. 100 Treg cells apply their function partially through secretion of anti-inflammatory cytokines such as IL-10…”

Section: Lit For Patients With Rplmentioning

confidence: 99%

Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

Taheri

Nejabati

Latifi

et al. 2018

American J Rep Immunol

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Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi-allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti-paternal cytotoxic antibodies (APCA), progesterone-induced blocking factor (PIBF), anti-idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR-Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT.

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“…Most studies observed an augmentation of Treg in peripheral blood and decidua during the first and second trimester in normal pregnant women (Heikkinen et al 2004;Xiong et al 2013;Tilburgs et al 2006). In the third trimester, Treg levels begin to decrease (Seol et al 2008) and further decline with successive stages of labor (Xiong et al 2010). Furthermore, Treg suppressive capacity is reduced in term labor and preterm labor suggesting that changes in Treg function may contribute to initiation of labor (Kisielewicz et al 2010).…”

Section: Regulatory T Cells In Human and Murine Pregnancymentioning

confidence: 99%