Regulatory T-Cells in Pregnancy: Historical Perspective, State of the Art, and Burning Questions

Ruocco, Maria Grazia; Chaouat, G.; Flórez, Laura; Bensussan, Armand; Klatzmann, David

doi:10.3389/fimmu.2014.00389

Cited by 91 publications

(82 citation statements)

References 127 publications

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“…7B). These findings support the involvement of immature DCs in the establishment of tolerogenic microenvironments, and they are in line with the importance of the cross-talk between Tregs and DCs for maintenance of tolerance (12). Treg-mediated suppression of DC function is mediated at least in part by the interaction of CTLA4 on Tregs with CD80/ CD86 on DCs.…”

Section: Discussionsupporting

confidence: 68%

“…The first viviparous mammals were faced with the development of a sophisticated adaptive immune system (12). The development of placentation in eutherians required the co-development of immune suppression mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…The discovery of Tregs, which are key players in immune tolerance, has uncovered their seemingly similar role in the two processes (12). In human pregnancy, Tregs are enriched at the maternal-fetal interface throughout healthy pregnancy (13,14), whereas a decreased Treg pool is observed in recurrent miscarriage cases (15) and preeclampsia (16).…”

mentioning

confidence: 99%

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Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice

Nehar-Belaid

Courau

Dérian

et al. 2016

The Journal of Immunology

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice

Nehar-Belaid

Courau

Dérian

et al. 2016

The Journal of Immunology

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“…Alongside well-known and deeply investigated immune adaptations involving dendritic cells (Segerer et al 2012), T cells (Ruocco et al 2014), NK cells (Parham 2004) and macrophages (Faas et al 2014), the B cell compartment was recently demonstrated to undergo profound modifications and adaptations during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Marginal zone B cells emerge as a critical component of pregnancy well-being

Muzzio¹,

Ziegler²,

Ehrhardt³

et al. 2016

Reproduction

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The success of eutherian mammal evolution was certainly supported by the ability of the already existing immune system to adapt to the presence of the semi-allogeneic fetus without losing the capability to defend the mother against infections. This required the acquisition of highly regulated and coordinated immunological mechanisms. Failures in the development of these strategies not only lead to the interruption of pregnancy but also compromise maternal health. Alongside changes on the cytokine profile -expansion of tolerogenic dendritic and regulatory T cells -a profound adaptation of the B cell compartment during pregnancy was recently described. Among others, the suppression of B cell lymphopoiesis and B cell lymphopenia were proposed to be protective mechanisms tending to reduce the occurrence of autoreactive B cells that might recognize fetal structures and put pregnancy on risk. On the other hand, expansion of the pre-activated marginal zone (MZ) B cell phenotype was described as a compensatory strategy launched to overcome B cell lymphopenia thus ensuring a proper defense. In this work, using an animal model of pregnancy disturbances, we demonstrated that the suppression of B cell lymphopoiesis as well as splenic B cell lymphopenia occur independently of pregnancy outcome. However, only animals undergoing normal pregnancies, but not those suffering from pregnancy disturbances, could induce an expansion and activation of the MZ B cells. Hence, our results clearly show that MZ B cells, probably due to the production of natural protective antibodies, participate in the fine balance of immune activation required for pregnancy well-being.

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“…Although the mechanisms of action of Th1-and Th2-type cytokines produced by maternal CD4+ T helper lymphocytes present at the fetomaternal interface are defined with respect to conceptus tolerance/pregnancy maintenance or are conceptus rejection/ failure of pregnancy [20][21][22][23][24], the mechanisms of action of CD4+CD25+Foxp3+ T reg cells present during human pregnancy are not so clear [25]. It was suggested in human pregnancy that T reg cells could inhibit the majority of human T cells that spontaneously proliferate and produce IFN-γ [26].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce Interleukin-4

Lombardelli

Logiodice

Aguerre-Girr

et al. 2017

Journal of Reproductive Immunology

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Background: Trophoblast expressing paternal HLA-C antigens resemble a semiallograft, and could be rejected by maternal CD4+ T lymphocytes. We examined the possible role in human pregnancy of Th17 cells, known to be involved in allograft rejection and reported for this reason to be responsible for miscarriages. We also studied Th17/ Th1 and Th17/Th2 cells never investigated before. We defined for the first time the role of different Th17 subpopulations at the embryo implantation site and the role of HLA-G5, produced by the trophoblast/embryo, on Th17 cell differentiation. Methods:Cytokine production by CD4+ purified T cell and T clones from decidua of normal pregnancy, unexplained recurrent abortion, and ectopic pregnancy at both embryo implantation site and distant from that site were analyzed for protein and mRNA production. Antigen-specific T cell lines were derived in the presence and in the absence of HLA-G5. Results:We found an associated spontaneous production of IL-17A, IL-17F and IL-4 along with expression of CD161, CCR8 and CCR4 (Th2-and Th17-type markers) in fresh decidua CD4+ T cells during successful pregnancy. There was a prevalence of Th17/Th2 cells (producing IL-17A, IL-17F, IL-22 and IL-4) in the decidua of successful pregnancy, but the exclusive presence of Th17 (producing IL-17A, IL-17F, IL-22) and Th17/Th1 (producing IL-17A, IL-17F, IL-22 and IFN-γ) cells was found in the decidua of unexplained recurrent abortion. More importantly, we observed that Th17/Th2 cells were exclusively present at the embryo implantation site during tubal ectopic pregnancy, and that IL-4, GATA-3, IL-17A, ROR-C mRNA levels increased in tubal biopsies taken from embryo implantation sites, whereas Th17, Th17/Th1 and Th1 cells are exclusively present apart from implantation sites. Moreover, soluble HLA-G5 mediates the development of Th17/Th2 cells by increasing IL-4, IL-17A and IL-17F protein and mRNA production of CD4+ T helper cells. Conclusion:No pathogenic role of decidual Th17 cells during pregnancy was observed. Indeed, a beneficial role for these cells was observed when they also produced IL-4. HLA-G5 could be the key feature of the uterine microenvironment responsible for the development of Th17/Th2 cells, which seem to be crucial for successful embryo implantation.

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Regulatory T-Cells in Pregnancy: Historical Perspective, State of the Art, and Burning Questions

Cited by 91 publications

References 127 publications

Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice

Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice

Marginal zone B cells emerge as a critical component of pregnancy well-being

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce Interleukin-4

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