Abstract
Regulatory T cells (Tregs) are a specialized subset of T lymphocytes that function as suppressive immune cells and inhibit various elements of immune response in vitro and in vivo. While there are constraints on the number or function of Tregs which can be exploited to evoke an effective anti-tumor response, sufficient expansion of Tregs is essential for successful organ transplantation and for promoting tolerance of self and foreign antigens. The immune-suppressive property of Tregs equips this T lymphocyte subpopulation with a pivotal role in the establishment and maintenance of maternal tolerance to fetal alloantigens, which is necessary for successful pregnancy. Elevation in the level of pregnancy-related hormones including estrogen, progesterone and human chorionic gonadotropin promotes the recruitment and expansion of Tregs, directly implicating these cells in the regulation of fetal-maternal immune tolerance. Current studies have provided evidence that a defect in the number or function of Tregs contributes to the etiology of several reproductive diseases, such as recurrent spontaneous abortion, endometriosis, and pre-eclampsia. In this review, we provide insight into the underlying mechanism through which Tregs contribute to pregnancy-related immune tolerance and demonstrate the association between deficiencies in Tregs and the development of reproductive diseases.
Highlights
Regulatory T cells (Tregs), a key subset of T lymphocytes, play a critical role in regulating the immune response and maintaining immune tolerance both in physiological and pathological processes
Khil et al reported that human chorionic gonadotropin (HCG) prevents the development of autoimmune-mediated diabetes in NOD mice by downregulating immune effector cells and cytokines and simultaneously upregulating the proportion of Tregs and the levels of TGF-β and IL-10, suggesting that HCG is an effective regulator for immune tolerance [114]
Since it has been determined that Tregs maintain fetal-maternal tolerance during the normal course of embryo implantation and pregnancy, it is of interest to investigate whether systemic and local maldistribution and dysfunction of Tregs play a role in the etiology of infertility and pregnancy-related complications
Summary
Regulatory T cells (Tregs), a key subset of T lymphocytes, play a critical role in regulating the immune response and maintaining immune tolerance both in physiological and pathological processes. Immune tolerance to the fetus is necessary for successful pregnancy, and transmission of seminal fluid seems to play a priming role prior to implantation by promoting expansion of Tregs, thereby activating specific tolerance to paternal alloantigens. A seemingly opposite pro-inflammatory process is involved in both implantation and initiation of labor, immunosuppression is an indispensable response to maintain immune homeostasis during the fetal growth stage, and this is highly dependent on the expansion and activation of Tregs triggered by the fetal alloantigens [93].
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