Antigenic Heterogeneity of Vascular Endothelium

Page, Christopher; Rose, Marlene L.; Yacoub, Magdi H.; Pigott, Rod

doi:10.1007/978-1-4615-3736-6_51

Cited by 176 publications

(186 citation statements)

References 33 publications

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“…Endothelial cells are known to be phenotypically heterogeneous in a manner that varies not only with vessel size (31,32) but also within microvascular populations (33)(34)(35)(36)(37). Our results support this: RMEC constitutively express HLA-DR in vivo, whereas endothelial cells from larger vessels do not; lower levels of CD31 on cultured RMEC distinguish them from HUVEC and cultured human lung microvascular endothelial cells; vWF expression is variable within a population of RMEC that otherwise have a uniform phenotype.…”

Section: Discussionsupporting

confidence: 73%

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

Muczynski¹,

Ekle²,

Coder³

et al. 2003

Journal of the American Society of Nephrology

145

107

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Abstract. Human, but not murine, renal peritubular and glomerular capillaries constitutively express class II major histocompatibility (MHC) proteins at high levels in normal human kidney. Expression of class II proteins on renal microvascular endothelial cells (RMEC) makes it available to circulating lymphocytes and imparts a surveillance capacity to RMEC for controlling inflammatory responses. In this report, the coexpression of HLA-DR and the endothelial marker CD31 are used to identify RMEC as a distinct population of cells within a standard renal biopsy using flow cytometry. A three-laser, multicolor flow cytometry analysis using Alexa dyes, developed for characterizing the expression of cell surface antigens, identifies RMEC as a population separate from HLA-DRexpressing leukocytes. HLA-DR RMEC co-express HLA-DP and HLA-DQ. RMEC also express the T cell costimulatory factor CD58 but not CD80, CD86, or CD40. On the basis of high HLA-DR expression, RMEC are isolated for culture using fluorescence-activated cell sorting and magnetic beads. Cultured RMEC require normal basal physiologic concentrations of gamma interferon (␥IFN) to maintain HLA protein expression. This expression is regulated by CIITA, the MHC class II-specific transcription factor. Four tissue-specific promoters have been described for CIITA. In freshly isolated RMEC, RT-PCR and hybridization using specific oligonucleotide probes to CIITA promoter sequences identify only the statinsensitive ␥IFN-induced promoter IV of CIITA. Therefore, the constitutive expression of HLA-DR on RMEC in normal human kidney is located in a position for immune surveillance, depends on basal physiologic concentrations of ␥IFN, and may be amenable to regulation with statins.MHC proteins are of two classes distinguished on the basis of structure and function. Class I molecules, composed of a polymorphic subunit complexed with ␤-2-microglobulin, are found on all nucleated cells and present antigenic peptides to CD8ϩ T lymphocytes; class II molecules, composed of polymorphic ␣ and ␤ chains, are constitutively expressed on a limited number of cell types (dendritic cells, macrophages, B lymphocytes) and present antigenic peptides to CD4 ϩ T lymphocytes. We recently described an unusual expression of MHC class II proteins in normal human kidneys that is not found in murine kidneys (1). The human MHC class II protein HLA-DR is abundantly expressed on peritubular and glomerular capillary endothelial cells but not on endothelial cells of larger blood vessels of normal kidney. Antibodies to HLA-DR and CD31, a protein highly expressed on endothelial cells, co-localize on peritubular and glomerular cells within sections of kidney tissue, indicating capillary endothelial cell location of HLA-DR. HLA-DR has also been identified on rare scattered circulating leukocytes found within the kidney, but over 98% of the DR identified by immunofluorescence microscopy in kidney cortex is located on capillary endothelial cells (1). We refer to these cells co-expressing HLA-DR and CD31 as rena...

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Section: Discussionsupporting

confidence: 73%

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

Muczynski¹,

Ekle²,

Coder³

et al. 2003

Journal of the American Society of Nephrology

145

107

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“…It is known that MHC class II is widely expressed within the vasculature in human, but not rodent, organs, particularly on microvascular, although also to a lesser extent, on large vessel endothelial cells (1)(2)(3). A number of groups have shown that IFN-␥-treated large vessel endothelial cells cause alloproliferation of resting CD4 ϩ T cells in vitro, allowing them to postulate that constitutively HLA class II-positive endothelial cells cause allostimulation of resting T cells in vivo (4 -6).…”

mentioning

confidence: 99%

“…To further dissect the responses of allospecific resting peripheral CD4 ϩ T cells to nonprofessional APC, we have permanently transfected two cell lines with a construct containing the full-length cDNA for class II transactivator (CIITA), 3 previously described as a regulator of the expression of HLA class II and related molecules, both in vivo and in vitro (18,19). In this way we have induced expression of HLA class II without the pleiotropic effects of IFN-␥.…”

mentioning

confidence: 99%

An Epithelial Cell Line That Can Stimulate Alloproliferation of Resting CD4+ T Cells, But Not After IFN-γ Stimulation

McCormack

Moyes

Shi

et al. 2000

The Journal of Immunology

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It has previously been shown that IFN-γ-induced up-regulation of HLA class II on the surface of epithelial cells is not sufficient to induce proliferation of allospecific CD4+ T cells in vitro. To further investigate this phenomenon, a human epithelial bladder carcinoma, T24, was induced to constitutively express HLA class II without IFN-γ stimulation, by permanent transfection with the full-length class II transactivator (CIITA) gene. Proliferation of allospecific T cells to transfected and wild-type cells with and without prior activation with saturating levels of IFN-γ for 4 days was examined. IFN-γ-activated T24 did not induce any response from CD4+ T cells. However, T24.CIITA induced significant levels of alloproliferation, which could be abrogated by pretreatment of T24.CIITA with a mAb to LFA-3. Prestimulation of T24.CIITA with saturating levels of IFN-γ for 4 days also prevented allospecific CD4+ T cell proliferation. These findings suggest that epithelial cells may be intrinsically able to process and present alloantigen and provide adequate costimulation. We propose that IFN-γ has a secondary, as yet unidentified, effect that acts to negatively regulate this response, at least in some epithelial cells.

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“…The much poorer relaiionship between arterial thrombotic events and anti-endothelial cell antibodies detected by immunoblotting with venous cndothelium. may be due to well recognized antigenic dilTercnces between venous and arterial endothelium [25]. Such a possibility could be further investigated by immunoblotting studies which compared endothelium obtained from various arterial sources with those of venous origin.…”

Section: Discussionmentioning

confidence: 99%

“…The enrichment of the membrane preparations and freedom 10 15 20 Concentration (jig/ml) 25 30 from cross-contamination of the cytosol fractions prepared from HUVEC were established by an ELISA which used a MoAb EN4 (Bradsurc Biologicals, Loughborough, UK) which is known to react with membrane epitopes which are retained on cultured HUVEC [21]. ELISA plates were coated overnight at 4^C with 0-30 ^g/ml of either membrane or cytosol preparation solubilized in 25 mM carbonate bulTer pH 9-6 and then incubated, after washing and blocking with PBS, 01% Tween 20 and PBS 01%.…”

Section: Ititegrity Of Membrane Ami Cytosol Fractions Of Huvecmentioning

confidence: 99%

Characterization and specificity of anti-endothelial cell membrane antibodies and their relationship to thrombosis in primary antiphospholipid syndrome (APS)

Hill

Phipps

Malia

et al. 1995

Clinical and Experimental Immunology

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SUMMARYImmunoblotting was used to detect antibodies reacting with membrane and cytosol preparations of human umbilical vein endothelial cells (HUVEC), fibroblasts and a T lymphoma line HUT78in 18 patients with anticardiolipiii antibodies (ACA) (14 of whom had had a thrombotic event), II patients with a recent myocardial infarction and 17 controls. Multiple membrane-specific antibodies to HUVEC were found in 10 ofthe patients with ACA (28 bands) and in nine ofthe patients with thromboses (27 bands) in contrast to only three ofthe patients with myocardial infarction (four bands) and one control (one band). The most frequently recognized HUVEC membrane epitopes were at 33 kD (four sera), 61-63 kD (five sera) and 76-79 kD (four sera). Although crossreactivity with fibroblast and/or HUT78 membranes was seen at 33 kD. binding at 61-63 kD and 76-79 kD was specific for endothelial membranes. Although no correlations with the presence and titre of ACA were seen, HUVEC membrane-specific antibodies showed a correlation with venous thrombotic events.

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Antigenic Heterogeneity of Vascular Endothelium

Cited by 176 publications

References 33 publications

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells

An Epithelial Cell Line That Can Stimulate Alloproliferation of Resting CD4+ T Cells, But Not After IFN-γ Stimulation

Characterization and specificity of anti-endothelial cell membrane antibodies and their relationship to thrombosis in primary antiphospholipid syndrome (APS)

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