<b>Alloproliferation of purified CD4<sup>+</sup> T cells to adult human heart endothelial cells, and study of second‐signal requirements</b>

McDouall, Rhoda; Page, Christopher; Hafizi, Sassan; Yacoub, Magdi H.; Rose, Marlene L.

doi:10.1046/j.1365-2567.1996.d01-736.x

Cited by 33 publications

(21 citation statements)

References 30 publications

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“…HLA-DM and Ii were also up-regulated on both cell lines. It was then shown that CIITA transfection did not alter cell surface expression of LFA-3, known to be a second signal for endothelial cell-mediated stimulation of CD4 ϩ T cells (17,28,34). Expression of ICAM-1, CD40, and HLA class I also remained unaltered after CIITA transfection.…”

Section: Discussionmentioning

confidence: 98%

“…There is a broad agreement that HLA class II-positive endothelial cells (5,6,16,28,29), but not epithelial cells (7,(11)(12)(13)(14)30), fibroblasts (31,32), or smooth muscle cells (28,33), cause alloproliferation of resting CD4 ϩ T cells. The advantage of CIITA transfection is that it can cause up-regulation of HLA-class II molecules without the pleiotropic effects of IFN-␥.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

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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“…Whereas CD80 and CD86, which provide the major costimulation for unprimed T cell responses, are lacking on RMEC, CD58, which has been associated with HLA-DR-initiated T cell activation in allogeneic assays with cardiac microvascular endothelial cells (39), is abundant on RMEC. CD40 is not normally expressed on RMEC in vivo, but a low level of CD40 is consistently induced by unknown factors in our cultured RMEC.…”

Section: Discussionmentioning

confidence: 99%

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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“…ϩ T cells after coculture with cytokine-activated human endothelial cells, others have reported the inability of cytokine-activated endothelium to initiate CD4 ϩ alloresponses (8,(25)(26)(27). Similar to human endothelium, MHC class II is induced after treatment with IFN-␥ on cultured mouse vascular endothelium (12,13).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelium Does Not Activate CD4+ Direct Allorecognition in Graft Rejection

Kreisel¹,

Krasinskas

Krupnick³

et al. 2004

The Journal of Immunology

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Expression of MHC class II by donor-derived APCs has been shown to be important for allograft rejection. It remains controversial, however, whether nonhemopoietic cells, such as vascular endothelium, possess Ag-presenting capacity to activate alloreactive CD4+ T lymphocytes. This issue is important in transplantation, because, unlike hemopoietic APCs, allogeneic vascular endothelium remains present for the life of the organ. In this study we report that cytokine-activated vascular endothelial cells are poor APCs for allogeneic CD4+ T lymphocytes in vitro and in vivo despite surface expression of MHC class II. Our in vitro observations were extended to an in vivo model of allograft rejection. We have separated the allostimulatory capacity of endothelium from that of hemopoietic APCs by using bone marrow chimeras. Hearts that express MHC class II on hemopoietic APCs are acutely rejected in a mean of 7 days regardless of the expression of MHC class II on graft endothelium. Alternatively, hearts that lack MHC class II on hemopoietic APCs are acutely rejected at a significantly delayed tempo regardless of the expression of MHC class II on graft endothelium. Our data suggest that vascular endothelium does not play an important role in CD4+ direct allorecognition and thus does not contribute to the vigor of acute rejection.

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Alloproliferation of purified CD4⁺ T cells to adult human heart endothelial cells, and study of second‐signal requirements

Cited by 33 publications

References 30 publications

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

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

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

Vascular Endothelium Does Not Activate CD4+ Direct Allorecognition in Graft Rejection

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Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second‐signal requirements

Cited by 33 publications

References 30 publications

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

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

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

Vascular Endothelium Does Not Activate CD4+ Direct Allorecognition in Graft Rejection

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Alloproliferation of purified CD4⁺ T cells to adult human heart endothelial cells, and study of second‐signal requirements