Maternal Acceptance of the Fetus: True Human Tolerance

Guleria, Indira; Sayegh, Mohamed H.

doi:10.4049/jimmunol.178.6.3345

Cited by 207 publications

(203 citation statements)

References 94 publications

(96 reference statements)

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“…It is the most common early pregnancy (10). Since HM is a pregnancy-based tumor, it is worth investigating how the presence of this pregnancy-related subpopulation of T cells, together with classical T cells (CD3 + T cells), are involved in tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Decidual infiltration of FoxP3+ regulatory Tï¿½cells, CD3+ Tï¿½cells, CD56+ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies

et al. 2011

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Abstract. Hydatidiform moles are considered pre-cancerous lesions of gestational trophoblastic neoplasia and are associated with an aberrant immune response. This preliminary study aimed to evaluate the feasibility of measuring the presence of immune cells as potential prognostic markers for hydatidiform moles. + trophoblast cells were highest in the gestational trophoblastic neoplasias (688/1,000 trophoblast cells) and lowest in the partial moles (87/1,000 trophoblast cells). Our results suggest that regulatory T cells may be involved in the progression of complete hydatidiform moles. A larger cohort study is required to assess whether immune cells are effective prognostic markers in gestational trophoblastic diseases. IntroductionHydatidiform moles (HM) or molar pregnancy is a unique entity among gestational trophoblastic diseases (GTDs), characterized by abnormal proliferation of placental trophoblasts accompanied by an excess of paternal genes. This pathological form of pregnancy persists until the 1st trimester before clinical symptoms become evident (1-4). The incidence of HM is highest in Asian countries and comparatively low in Western countries (5,6). HM appears as complete moles (CM) or partial moles (PM), based on histopathological features and karyotypes that confer the potential for local invasion and widespread metastasis. The level of aggressiveness varies according to mole type; they may lead to persistent disease or post-molar gestational trophoblastic neoplasia (GTN). Thus, HMs are considered the pre-cancerous lesions of GTN (3,7).Most CMs are cytogenetically diploid with a 46XX karyotype. Both sets of chromosomes are of paternal origin, since the CM results from fertilization of an empty ovum by a haploid (23X) spermatozoa; alternatively, dispermic CMs develop from an empty ovum fertilized by two haploid (23X and/or 23Y) spermatozoa. Both types of CMs are totally paternally derived and represent a complete intrauterine allograft in the mother. In contrast to CMs, PMs are generally triploid; PMs retain maternal chromosomes, but also have an excess set of paternal chromosomes. PMs result from fertilization of a normal haploid ovum (23X) by two haploid spermatozoa (3,4,7). In CMs, the complete allograft conceptus is expected to provoke a maternal immune response, with immune cell invasion leading to rejection. PMs may also provoke an altered immune response compared to normal pregnancy (NP), due to the excess paternal genetic material.Ectopic pregnancy (EP) is another type of first trimester abnormal pregnancy. It is the most common early pregnancy

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Section: Introductionmentioning

confidence: 99%

Decidual infiltration of FoxP3+ regulatory Tï¿½cells, CD3+ Tï¿½cells, CD56+ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies

et al. 2011

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“…One means to address this challenge could be provided by the use of embryonic porcine tissue. This strategy is based on the growing evidence, over the past 5 decades, demonstrating maternal immune tolerance to the fetus (2,3), and on recent observations that embryonic tissues exhibit reduced immunogenicity in various transplantation settings (4)(5)(6)(7). Considering that very early embryonic tissues are associated with a substantial risk of teratoma formation, we have attempted, during the past several years, to define the earliest gestational time point that does not pose a teratoma risk for transplantation of different embryonic pig tissues, including kidney (6), heart (unpublished), spleen (8), pancreas, liver, and lung (7) into SCID mice.…”

mentioning

confidence: 99%

Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model

Hecht

Eventov‐Friedman

Rosen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a ␤ cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes.immune-suppression ͉ rejection ͉ xeno-transplantation

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“…It has been argued that reducing B and T lymphocyte production during pregnancy might be a way of preventing entry into the naive lymphocyte pool of cells bearing receptors potentially reactive against paternal alloantigens. So far, many mechanisms, including augmentation of the lymphocyte activation threshold, redistribution of lymphocyte subsets or mobilization of T reg and NK cells to the placenta, have been proposed to explain the enigmatic maternal "tolerance" of the allogenic fetus (recently reviewed in [51]). In our study, restoring B lymphopoiesis during pregnancy by either IL-7 injection or use of IL-7-transgenic mice has not resulted in any obvious perturbation of pregnancy, even in situations where pregnant mice were bearing H-2 allogenic fetuses (R.C.…”

Section: Discussionmentioning

confidence: 99%

Transient decrease in interleukin‐7 availability arrests B lymphopoiesis during pregnancy

2008

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In mice, B lymphopoiesis is transiently arrested during pregnancy, and this is thought to be due to depletion of a hormone-sensitive bone marrow precursor. In this study, combining in vitro and in vivo approaches with detailed phenotypic and functional analysis of progenitor cells, we have investigated the effects of pregnancy on mouse B cell development. Recently, we characterized a BM progenitor called early progenitor with lymphoid and myeloid potential (EPLM) which, when cultured under B cell conditions, is the immediate precursor of pre-B1 cells. Results obtained show that during late pregnancy, B cell development was blocked at the EPLM-to-pre-B1 transition. This block was associated with a lack of IL-7 due to a down-regulation of IL-7 gene transcription. Moreover, we established that exogenously administered IL-7 could rescue B lymphopoiesis in pregnant mice. We conclude that during pregnancy, rather than directly depleting a hormone-sensitive B cell precursor, hormones dampen BM B cell development by fine-tuning IL-7 availability.

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Maternal Acceptance of the Fetus: True Human Tolerance

Cited by 207 publications

References 94 publications

Decidual infiltration of FoxP3+ regulatory Tï¿½cells, CD3+ Tï¿½cells, CD56+ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies

Decidual infiltration of FoxP3+ regulatory Tï¿½cells, CD3+ Tï¿½cells, CD56+ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies

Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model

Transient decrease in interleukin‐7 availability arrests B lymphopoiesis during pregnancy

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