Expression of HLA class I molecules in human first trimester and term placenta trophoblast

Hutter, Heinz; Hammer, Astrid; Blaschitz, Astrid; Hartmann, Michaele; Ebbesen, Peter; Dohr, Gottfried; Ziegler, Andreas; Uchańska-Ziegler, Barbara

doi:10.1007/s004410050713

Cited by 89 publications

(53 citation statements)

References 35 publications

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“…The A-LAP and 3F5 antibodies were raised against ERAP1 and ERAP2, respectively (15,20). MHC I was detected by Western blotting using R5996-4 (21) and by flow cytometry using W6/32 (22) and the HLA-A locus-specific TU155 (23). The antibodies to MYCN, p50, p65, and proliferating cell nuclear antigen (PCNA) were from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells

et al. 2010

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Neuroblastoma (NB) is the most common solid extracranial cancer of childhood. Amplification and overexpression of the MYCN oncogene characterize the most aggressive forms and are believed to severely downregulate MHC class I molecules by transcriptional inhibition of the p50 NF-κB subunit. In this study, we found that in human NB cell lines, high MYCN expression is not responsible for low MHC class I expression because neither transfection-mediated overexpression nor small interfering RNA suppression of MYCN affects MHC class I and p50 levels. Furthermore, we identified NF-κB as the immediate upstream regulator of MHC class I because the p65 NF-κB subunit binds MHC class I promoter in chromatin immunoprecipitation experiments, and MHC class I expression is enhanced by p65 transfection and reduced by (a) the chemical NF-κB inhibitor sulfasalazine, (b) a dominant-negative IKBα gene, and (c) p65 silencing. Moreover, we showed that the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2, which generate MHC class I binding peptides, are regulated by NF-κB, contain functional NF-κB-binding elements in their promoters, and mimic MHC class I molecules in the expression pattern. Consistent with these findings, nuclear p65 was detected in NB cells that express MHC class I molecules in human NB specimens. Thus, the coordinated downregulation of MHC class I, ERAP1, and ERAP2 in aggressive NB cells is attributable to a low transcriptional availability of NF-κB, possibly due to an unknown suppressor other than MYCN. Cancer Res; 70(3); 916-24. ©2010 AACR.

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Section: Methodsmentioning

confidence: 99%

NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells

et al. 2010

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“…Following implantation, the decidualised endometrium, a tissue containing a large population of leucocytes (King & Loke 1991, Stallmach et al 1995, is rapidly infiltrated by foetally derived extravillous trophoblast cells (EVT; Kurman et al 1984, Yeh et al 1991, which express the paternally derived non-self HLA antigens, HLA-G, HLA-E and HLA-C (Houlihan et al 1995, Hutter et al 1996, King et al 1996. In normal pregnancy, w30-40% of decidual stromal cells are leucocytes (Bulmer et al 1991); in the first trimester, uterine natural killer (uNK) cells account for up to 70%, macrophages up to 30% (Bulmer et al 1988) and T-lymphocytes fewer than 20% (Bulmer et al 1991) of the total leucocyte population (Bulmer et al 1991, King & Loke 1991, Klentzeris et al 1992.…”

Section: Introductionmentioning

confidence: 99%

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Williams¹,

Bulmer²,

Searle³

et al. 2009

Reproduction

150

113

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Alterations in the balance of leucocyte populations in uterine decidua may lead to the generation of an unfavourable cytokine environment that is associated with unsuccessful pregnancy. Single and double immunohistochemical labelling was used to examine leucocyte populations in decidua from normal third trimester, foetal growth-restricted and pre-eclamptic pregnancies. Placental bed biopsies from 12 women undergoing elective Caesarean section with no hypertension or foetal growth restriction (FGR), 8 women with FGR without maternal hypertension and 12 women with pre-eclampsia (PE) were used to quantify decidual CD56C uterine NK cells, CD14C macrophages, CD3CT-lymphocytes and CD8C lymphocytes. CD3CCD56C, CD8CCD56C and CD161CCD3C double-labelled cells in decidua were compared in PE and control decidua. Decidual CD3CT-lymphocytes (P!0.01), CD8C cytotoxic T-lymphocytes (P!0.05), CD14C macrophages (P!0.0001) and CD56C uterine natural killer (uNK) cells (PZ0.01) were decreased in placental bed biopsies from women with PE compared with control third trimester decidua. By contrast, only CD56C uNK cells were decreased in FGR decidua (P!0.05). Double-positive CD8CCD56C cells were also decreased in PE compared with control third trimester decidua (P!0.05). The reduction in specific leucocyte subset numbers in PE and uNK cells in FGR suggests that altered local cytokine balance may be important in defective trophoblast invasion and spiral artery transformation in these pathological pregnancies.

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“…These epithelial cells possess several intriguing features that suggest a role for these cells in preventing fetal rejection. Trophoblasts express little or no classical MHC class I (HLA-A, -B, and -C) (2)(3)(4)(5), but do express a number of nonclassical MHC class I molecules. Examples include HLA-E (6) and HLA-G (7,8), which can modulate the innate immune response and prevent NK (6) and NK T cell (9)-mediated cytotoxicity.…”

mentioning

confidence: 99%

“…We have previously described a subset of CD8 ϩ regulatory T cells in humans that is restricted by CD1d and a costimulatory molecule of the carcinoembryonic Ag (CEA) 3 family expressed on intestinal epithelial cells (IEC). These cells use a restricted TCR repertoire (V␤5.1/V␣18), are CD28 Ϫ , and can suppress immune responses in vitro (11).…”

mentioning

confidence: 99%

Activation of CD8+ Regulatory T Cells by Human Placental Trophoblasts

Shao¹,

Jacobs

Johnson

et al. 2005

The Journal of Immunology

102

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The immunological basis by which a mother tolerates her semi-allogeneic fetus remains poorly understood. Several mechanisms are likely to contribute to this phenomenon including active immune regulation by regulatory T cells. In this article, we report that human placental trophoblasts activate a clonal population of CD8+ T cells with regulatory function. These cells are not MHC class I restricted, but require costimulation through a member of the carcinoembryonic Ag family present on early gestation trophoblasts. These regulatory T cells express the mucosal markers CD101 and CD103 and display selective usage of the TCR gene Vβ9. CD8+ T cells isolated from the peripheral blood of pregnant mothers (16–28 wk) also demonstrate expansions in the same Vβ family (Vβ9), signaling a possible role for these cells in preventing fetal rejection in vivo. We have previously characterized a subset of CD8+ regulatory T cells activated by the combination of the nonclassical class I molecule CD1d and a costimulatory molecule of the carcinoembryonic Ag family present on the intestinal epithelium. These data support the concept that distinct regulatory T cell populations exist at different sites and may be regulated locally by unique restriction elements, costimulatory signals, and Ags.

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Expression of HLA class I molecules in human first trimester and term placenta trophoblast

Cited by 89 publications

References 35 publications

NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells

NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells

Altered decidual leucocyte populations in the placental bed in pre-eclampsia and foetal growth restriction: a comparison with late normal pregnancy

Activation of CD8+ Regulatory T Cells by Human Placental Trophoblasts

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