Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Bas‐Bernardet, Stéphanie Le; Hourmant, Maryvonne; Coupel, Stéphanie; Bignon, Jean-Denis; Soulillou, Jean‐Paul; Charreau, Béatrice

doi:10.1034/j.1600-6143.2003.00021.x

Cited by 94 publications

(67 citation statements)

References 38 publications

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“…Endothelial Cell Culture and Activation-Human ECs were isolated from human umbilical veins (HUVECs) or aorta (HAECs) as previously described (20). ECs were cultured in endothelial cell growth medium supplemented with 10% fetal calf serum (FCS), endothelial cell growth supplement (0.4%), hydrocortisone (1 g/ml), human basic fibroblast growth factor (1 ng/ml), human epidermal growth factor (0.1 ng/ml), amphotericin B (50 ng/ml), and gentamicin (50 g/ml) (Promocell, Heidelberg, Germany) at 37°C in a 5% CO 2 humidified air incubator.…”

Section: Methodsmentioning

confidence: 99%

The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-α-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways

Fitau¹,

Boulday²,

Coulon³

et al. 2006

Journal of Biological Chemistry

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Lnk, with APS and SH2-B (Src homology 2-B), belongs to a family of SH2-containing proteins with potential adaptor functions. Lnk regulates growth factor and cytokine receptor-mediated pathways implicated in lymphoid, myeloid, and platelet homeostasis. We have previously shown that Lnk is expressed and up-regulated in vascular endothelial cells (ECs) in response to tumor necrosis factor-␣ (TNF␣). In this study, we have shown that, in ECs, Lnk down-regulates the expression, at both mRNA and protein levels, of the proinflammatory molecules VCAM-1 and E-selectin induced by TNF␣. Mechanistically, our data indicated that, in response to TNF␣, NFB/p65 phosphorylation and translocation as well as IB␣ phosphorylation and degradation were unchanged, suggesting that Lnk does not modulate NFB activity. However, Lnk activates phosphatidylinositol 3-kinase (PI3K) as reflected by Akt phosphorylation. Our results identify endothelial nitric-oxide synthase as a downstream target of Lnk-mediated activation of the PI3K/Akt pathway and HO-1 as a new substrate of Akt. We found that sustained Lnkmediated activation of PI3K in TNF␣-activated ECs correlated with the inhibition of ERK1/2 phosphorylation, whereas phosphorylation of p38 and c-Jun NH 2 -terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) was unchanged. ERK1/2 inhibition decreases VCAM-1 expression in TNF␣-treated ECs. Collectively, our results identify the adaptor Lnk as a negative regulator in the TNF␣-signaling pathway mediating ERK inhibition and suggest a role for Lnk in the interplay between PI3K and ERK triggered by TNF␣ in ECs.

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Section: Methodsmentioning

confidence: 99%

The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-α-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways

Fitau¹,

Boulday²,

Coulon³

et al. 2006

Journal of Biological Chemistry

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“…Human aortic ECs (HAECs) were isolated as previously described (18). HAECs were cultured in cell growth medium supplemented with 10% FCS, endothelial cell growth supplement (0.4%), hydrocortisone (1 g/ ml), human basic fibroblast growth factor (1 ng/ml), human epidermal growth factor (0.1 ng/ml), amphotericin B (50 ng/ml), and gentamicin (50 g/ml) (PromoCell) at 37°C and 5% CO 2 .…”

Section: Cell Purification Culture and Activationmentioning

confidence: 99%

The C-Type Lectin-Like Receptor CLEC-1, Expressed by Myeloid Cells and Endothelial Cells, Is Up-Regulated by Immunoregulatory Mediators and Moderates T Cell Activation

Thébault

Lhermite

Tilly

et al. 2009

The Journal of Immunology

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C-type lectin receptors have recently been described as playing crucial roles in immunity and homeostasis since these proteins are able to recognize pathogens as well as self-Ags. We identified the C-type lectin-like receptor-1, CLEC-1, as being overexpressed in a model of rat allograft tolerance. We previously described in this model the expression of numerous cytoprotective molecules by graft endothelial cells and their interplay with regulatory CD4+CD25+ T cells. In this study, we demonstrate that CLEC-1 is expressed by myeloid cells and specifically by endothelial cells in tolerated allografts and that CLEC-1 expression can be induced in endothelial cells by alloantigen-specific regulatory CD4+CD25+ T cells. Analysis of CLEC-1 expression in naive rats demonstrates that CLEC-1 is highly expressed by myeloid cells and at a lower level by endothelial cells, and that its expression is down-regulated by inflammatory stimuli but increased by the immunoregulators IL-10 or TGFβ. Interestingly, we demonstrate in vitro that inhibition of CLEC-1 expression in rat dendritic cells increases the subsequent differentiation of allogeneic Th17 T cells and decreases the regulatory Foxp3+ T cell pool. Additionally, in chronically rejected allograft, the decreased expression of CLEC-1 is associated with a higher production of IL-17. Taken together, our data suggest that CLEC-1, expressed by myeloid cells and endothelial cells, is enhanced by regulatory mediators and moderates Th17 differentiation. Therefore, CLEC-1 may represent a new therapeutic agent to modulate the immune response in transplantation, autoimmunity, or cancer settings.

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“…Human arterial endothelial cells (EC) from DR1 ϩ donors were isolated from renal artery patches taken before kidney transplantation, as described previously (27). EC were treated with recombinant human IFN-␥ (250 U/ml) 72 h before their use as stimulators.…”

Section: Target Cellsmentioning

confidence: 99%

EBV-Specific CD4+ T Cell Clones Exhibit Vigorous Allogeneic Responses

Landais

Morice

Long

et al. 2006

The Journal of Immunology

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Alloreactive T cells play a key role in mediating graft-vs-host disease and allograft rejection, and recent data suggest that most T cell alloreactivity resides within the CD4 T cell subset. Particularly, T cell responses to herpesvirus can shape the alloreactive repertoire and influence transplantation outcomes. In this study, we describe six distinct EBV-specific CD4+ T cell clones that cross-reacted with EBV-transformed lymphoblastoid cell lines (LCLs), dendritic cells, and endothelial cells expressing MHC class II alleles commonly found in the population. Allorecognition showed exquisite MHC specificity. These CD4+ T cell clones efficiently killed dendritic cells or LCLs expressing the cross-reactive allogeneic MHC class II molecules, whereas they did not kill autologous LCLs. Endothelial cells expressing the proper allogeneic MHC molecules were poorly killed, but they induced high-level TNF-α production by the EBV-specific CD4+ T cell clones. As already proposed, the strong alloreactivity toward LCLs suggest that these cells could be used for selective depletion of alloreactive T cells.

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Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Cited by 94 publications

References 38 publications

The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-α-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways

The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-α-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways

The C-Type Lectin-Like Receptor CLEC-1, Expressed by Myeloid Cells and Endothelial Cells, Is Up-Regulated by Immunoregulatory Mediators and Moderates T Cell Activation

EBV-Specific CD4+ T Cell Clones Exhibit Vigorous Allogeneic Responses

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