Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells

Tilburgs, Tamara; Scherjon, Sicco A.; Mast, Barbara J. van der; Haasnoot, Geert W.; Versteeg-v.d.Voort-Maarschalk, Minke; Roelen, Dave L.; Rood, J.J. van; Claas, Frans H.J.

doi:10.1016/j.jri.2009.05.003

Cited by 215 publications

(181 citation statements)

References 35 publications

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“…The increase in resting Treg after coculture with EVT demonstrates that EVT directly contributes to augmentation of the maternal Treg pool at the maternal-fetal interface. Although the mechanisms responsible remain unknown, the increase in FOXP3 and proportion of Treg may contribute to suppression of maternal immune responses directed to polymorphic fetal HLA-C molecules expressed on EVT (16). However, the antigen specificity of the Treg at the fetal-maternal interface as well as whether cell contact and/or soluble factors are required to promote Treg are questions of key importance to understanding maternal-fetal tolerance.…”

Section: Discussionmentioning

confidence: 99%

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Tilburgs

Crespo

Zwan

et al. 2015

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

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Invading human leukocyte antigen-G+ (HLA-G+) extravillous trophoblasts (EVT) are rare cells that are believed to play a key role in the prevention of a maternal immune attack on foreign fetal tissues. Here highly purified HLA-G+ EVT and HLA-G− villous trophoblasts (VT) were isolated. Culture on fibronectin that EVT encounter on invading the uterus increased HLA-G, EGF-Receptor-2, and LIFReceptor expression on EVT, presumably representing a further differentiation state. Microarray and functional gene set enrichment analysis revealed a striking immune-activating potential for EVT that was absent in VT. Cocultures of HLA-G+ EVT with sample matched decidual natural killer cells (dNK), macrophages, and CD4+ and CD8+ T cells were established. Interaction of EVT with CD4+ T cells resulted in increased numbers of CD4+CD25 HI FOXP3+CD45RA+ resting regulatory T cells (Treg) and increased the expression level of the Treg-specific transcription factor FOXP3 in these cells. However, EVT did not enhance cytokine secretion in dNK, whereas stimulation of dNK with mitogens or classical natural killer targets confirmed the distinct cytokine secretion profiles of dNK and peripheral blood NK cells (pNK). EVT are specialized cells involved in maternal-fetal tolerance, the properties of which are not imitated by HLA-G-expressing surrogate cell lines.Treg | FOXP3 | NK cell | human | pregnancy

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Section: Discussionmentioning

confidence: 99%

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Tilburgs

Crespo

Zwan

et al. 2015

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

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170

183

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“…40 In humans, extravillous trophoblasts express polymorphic histocompatibility antigen, HLA-C, which can elicit an allogeneic T-cellresponse. Tilburgs et al 41 recently reported that pregnancy with a HLA-C-mismatched child induces an increased percentage of activated T cells in decidual tissue. Interestingly, HLA-C-mismatched pregnancies exhibit significantly increased suppressive capacity in one-way MLR reaction to umbilical mononuclear cells, suggesting decidual Treg cells inhibit HLA-C-recognized-T-cell attack.…”

Section: Th1/th2/th17 and Treg Paradigms In Normal Pregnancymentioning

confidence: 99%

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

Saito

Nakashima

Saito

et al. 2010

American J Rep Immunol

1,002

833

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Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010T‐helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)‐β and interleukin (IL)‐10 or by cell‐to‐cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms.

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“…Dendritic cells (DC) promote cell tolerance particularly at the maternal-foetal interface, by priming T-regulatory (T reg ) cells (Blois et al 2007). T reg cells, part of the adaptive immune system play a pivotal role in promoting foetal survival by avoiding the recognition of semi-allogenic tissues by the maternal immune system (Somerset et al 2004, Tilburgs et al 2009, La Rocca et al 2014. This was seen in a mice model where depletion of CD25 + T reg cells led to gestation failure (Aluvihare et al 2004) and a certain systemic composition of T reg cells with distinct subsets have been associated with PTL (Steinborn et al 2011).…”

Section: :3mentioning

confidence: 99%

Myometrial cytokines and their role in the onset of labour

Sivarajasingam

Imami

Johnson

2016

Journal of Endocrinology

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Human labour is an inflammatory event, physiologically driven by an interaction between hormonal and mechanical factors and pathologically associated with infection, bleeding and excessive uterine stretch. The initiation and communicators of inflammation is still not completely understood; however, a key role for cytokines has been implicated. We summarise the current understanding of the nature and role of cytokines, chemokines and hormones and their involvement in signalling within the myometrium particularly during labour.

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Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells

Cited by 215 publications

References 35 publications

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy

Myometrial cytokines and their role in the onset of labour

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