Activation of CD8+ Regulatory T Cells by Human Placental Trophoblasts

Shao, Ling; Jacobs, Adam; Johnson, Valrie V.; Mayer, Lloyd

doi:10.4049/jimmunol.174.12.7539

Cited by 102 publications

(82 citation statements)

References 52 publications

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“…Trophoblasts play central parts in the development and maintenance of a successful pregnancy, as they modulate maternal immune cells to tolerate the fetus (32)(33)(34)(35)(36)(37). Invasive trophoblasts encounter maternal immune cells, particularly NK cells, which aid in uterine tissue invasion and remodeling of uterine spiral arteries (36).…”

Section: Discussionmentioning

confidence: 99%

Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal–Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells

Guo

Piao

et al. 2014

The Journal of Immunology

118

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Physiological pregnancy requires the maternal immune system to recognize and tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is not yet clear how the fetus evades the maternal immune system. In this article, we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP) instructs decidual CD11c+ dendritic cells (dDCs)with increased costimulatory molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines. TSLP-activated dDCs induce proliferation and differentiation of decidual CD4+CD25− T cells into CD4+CD25+FOXP3+ regulatory T cells (Tregs) through TGF-β1. TSLP-activated dDC–induced Tregs display immunosuppressive features and express Th2-type cytokines. In addition, decidual CD4+CD25+FOXP3+ Tregs promote invasiveness and HLA-G expression of trophoblasts, resulting in preferential production of Th2 cytokines and reduced cytotoxicity in decidual CD56brightCD16− NK cells. Of interest, decreased TSLP expression and reduced numbers of Tregs were observed at the maternal–fetal interface during miscarriage. Our study identifies a novel feedback loop between embryo-derived trophoblasts and maternal decidual leukocytes, which induces a tolerogenic immune response to ensure a successful pregnancy.

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Section: Discussionmentioning

confidence: 99%

Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal–Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells

Guo

Piao

et al. 2014

The Journal of Immunology

118

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“…Jenkinsson et al, first reported CD1d transcription in both trophoblast and choriocarcinoma cell lines (Jenkinson et al 1999), which was followed by the demonstration that CD1d is expressed on both the villous and extravillous trophoblasts and that its expression increases as gestation progresses (Boyson et al 2002;Shao et al 2005). In addition to trophoblasts in anchoring villi, CD1d is expressed on trophoblasts that have invaded well into the maternal decidua (Boyson et al 2002).…”

Section: Nkt Cells and Cd1d At The Maternal-fetal Interfacementioning

confidence: 99%

NKT Cells at the Maternal-Fetal Interface

Boyson

Aktan

Barkhuff

et al. 2008

Immunological Investigations

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Establishment of the maternal-fetal interface is characterized by the influx of maternal NK cells, macrophages, and T cells into the decidua. Although a great deal has been learned about the function of NK cells in the decidua, comparatively little is known of decidual T cell function. NKT cells are an unusual T cell subset capable of producing both Th1-like and Th2-like cytokines. Unlike conventional αβ T cells that recognize peptides in the context of MHC molecules, NKT cells recognize glycolipids presented by the MHC class I-like molecule, CD1d. Recent reports have demonstrated that NKT cells and CD1d are present at the maternal-fetal interface. Moreover, activation of NKT cells can have dramatic effects on pregnancy. In this article, we will review basic aspects of NKT cell biology and summarize the recent literature on NKT cells at the maternal-fetal interface.

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“…Fitting with the immunochemistry analysis, the graftinfiltrating cells contained relatively high numbers of CD103 ϩ cells compared with naive animals (Fig. 3) ϩ T cells with a CD103 ϩ CD45RC Ϫ CD62L low phenotype, a population that has also been described as being potentially regulatory/activated T cells (22,23).…”

Section: The Grafts Of Anti-donor Class Ii-treated Tolerant Recipientmentioning

confidence: 99%

Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells

Degauque

Lair

Dupont

et al. 2006

The Journal of Immunology

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Allograft acceptance can be induced in the rat by pretransplant infusion of donor blood or spleen cells. Although promoting long-term acceptance, this treatment is also associated with chronic rejection. In this study, we show that a single administration of anti-donor MHC class II alloimmune serum on the day of transplantation results in indefinite survival of a MHC-mismatched kidney graft. Long-term recipients accept a donor-type skin graft and display no histological evidence of chronic rejection. The kidney grafts of tolerant animals display an accumulation of TCR Cβ, FoxP3, and IDO transcripts. Moreover, as compared with syngeneic recipients, tolerant recipients harbor a large infiltrate of MHC class II+ cells and CD103+ cells. In vitro, splenocytes from tolerant recipients exhibit decreased donor-specific proliferation, which is restored by depletion of non-T cells and partially restored by the blockade of IDO. Finally, splenocytes from tolerant recipients, but not purified T cell splenocytes, transfer donor-specific infectious tolerance without chronic rejection, after infusion into naive recipients, over two generations. However, splenocytes depleted of T cells or splenocytes depleted of CD103+ cells fail to transfer tolerance. Collectively, these data show that a single administration of anti-donor MHC class II alloimmune serum induces a tolerant state characterized by an infiltration of the kidney graft by regulatory T cells and CD103+ cells. These data also show that the transfer of tolerance requires the presence of both T cells and CD103+ dendritic cells. The precise mechanism of cooperation of these two cell subsets remains to be defined.

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Activation of CD8+ Regulatory T Cells by Human Placental Trophoblasts

Cited by 102 publications

References 52 publications

Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal–Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells

Embryonic Trophoblasts Induce Decidual Regulatory T Cell Differentiation and Maternal–Fetal Tolerance through Thymic Stromal Lymphopoietin Instructing Dendritic Cells

NKT Cells at the Maternal-Fetal Interface

Dominant Tolerance to Kidney Allografts Induced by Anti-Donor MHC Class II Antibodies: Cooperation between T and Non-T CD103+ Cells

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