CD86 (B70/B7–2) on endothelial cells co-stimulates allogeneic CD4<sup>+</sup>T cells

Seino, Ken‐ichiro; Azuma, Miyuki; Bashuda, Hisashi; Fukao, Katashi; Yagita, Hideo; Okumura, Ko

doi:10.1093/intimm/7.8.1331

Cited by 42 publications

(32 citation statements)

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“…The role of endothelial cells in initiating a primary T-cell response is important in organ transplantation because the vascular endothelial cells of the allograft are the first target encountered with the recipient's immune system (Marelli-Berg et al, 1996). In vitro experiments showed that the vascular endothelial cells can function as resident APCs to CD4ϩ T cells (Maher et al, 1996;Seino et al, 1995). However, the ability of the endothelium to provide effective costimulatory signals for full T-cell activation was controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Another study suggested that the endothelial cells express neither CD80 nor CD86 (Ma and Pober, 1998). However, CD86-dependent costimulation was demonstrated in both the human umbilical vein endothelial cells and a porcine endothelial cell line (Maher et al, 1996;Seino et al, 1995). De Greef et al (2001) found the location of B7-1 (CD80) protein in the endothelial cells of the ascending vasa recta.…”

Section: Discussionmentioning

confidence: 99%

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Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Satoh

Suzuki

Asari

et al. 2002

Laboratory Investigation

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SUMMARY:Recent studies suggested that the vascular endothelial cells function as a resident antigen-presenting cell (APC) in certain situations such as organ transplantation, and the ischemia/reperfusion injury, an inevitable event in organ transplantation, leads to an enhanced biosynthesis of cell adhesion molecules. We have demonstrated that the hepatic sinusoidal endothelial cells have potential ability as APCs by expressing the costimulatory adhesion molecule proteins, CD80 (B7-1) and CD86 (B7-2), of which expression was enhanced by warm ischemia/reperfusion of the rat liver. In this study, we assessed the localization of CD80, CD86, and intercellular adhesion molecule 1 in the rat kidneys and the influence of warm ischemia/reperfusion with or without a hypercreatinemic condition on the expression of these adhesion molecules in the renal tissues. Wistar male rats weighing 150 to 230 g were divided into group A, receiving a sham-operation (control), group B, receiving 1-hour clamping of the left renal pedicle (temporary ischemia), and group C, receiving right nephrectomy and 1-hour clamping of the left renal pedicle (temporary ischemia with hypercreatinemia). The left kidneys were submitted to immunohistochemical and molecular analyses sequentially for the period of 14 days. We found that CD80, CD86, and intercellular adhesion molecule 1 proteins localized on the glomerular and peritubular endothelium and were up-regulated after ischemia/reperfusion. The up-regulation of these three proteins was enhanced by the hypercreatinemic condition. The relative mRNA levels analyzed by real-time reverse transcription polymerase chain reaction showed that CD80 and CD86 expressions were constitutively observed and significantly increased for 14 days after the warm ischemia reperfusion with a peak level at Day 3 (6.7-and 20.8-fold increase for CD80 and CD86, respectively). Our results suggested that the glomerular endothelial cells will play a pivotal role as a APC by expressing CD80 and CD86 in the induction of renal tissue injury associated with the ischemia/reperfusion at renal transplantation surgery, as well as the peritubular endothelium. (Lab Invest 2002, 82:1209 -1217.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Satoh

Suzuki

Asari

et al. 2002

Laboratory Investigation

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“…21 Previous experiments examining the ability of endothelial cells to express B7 costimulatory molecules have yielded disparate results. [43][44][45] We found that B7-1 was constitutively expressed at a low level on the surfaces of the cloned CVEs, and this level was unaffected by incubation with TNF-␣ (Figure 2). However, B7-1 expression was significantly increased upon stimulation with IFN-␥, and the level was further enhanced by incubation with IFN-␥ and TNF-␣ in combination.…”

mentioning

confidence: 99%

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Girvin

Gordon

Welsh

et al. 2002

Blood

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IntroductionThe brain has been considered an immune-privileged site in the presence of an intact blood-brain barrier (BBB). The BBB consists of tight junctions between cerebrovascular endothelial cells (CVEs), and it serves as a physical barrier limiting T-cell and antibody passage into the central nervous system (CNS). 1 Few unactivated T cells are capable of extravasating through the BBB, regardless of their antigen specificity, but low numbers of T cells can be found in the CNS of healthy humans and rats, so there appears to be a role for T-cell surveillance of the CNS in the absence of inflammation. Under these conditions, the low expression of major histocompatibility complex (MHC) class II and T-cell costimulation/adhesion molecules on CNS-resident cells renders the CNS an unsuitable site for T-cell priming. However, during an inflammatory immune response, the BBB is disrupted and all T cells and mononuclear cells have the ability to traffic into the brain and spinal cord and to recognize target antigens within the CNS. [2][3][4] Under these conditions, potential antigen-presenting cells (APCs) residing in the CNS are likely to play a major role in T-cell responses and may contribute to the propagation or regulation of inflammatory immune responses in the CNS, as they do in multiple sclerosis (MS).The BBB is damaged by demyelinating diseases such as MS and its animal model, experimental autoimmune encephalomyelitis (EAE). MS and EAE are characterized by CNS infiltration of myelin protein-specific Th1 cells, pro-inflammatory cytokine production of interferon-␥ (IFN-␥) and tumor necrosis factor-␣ (TNF-␣), mononuclear cell accumulation, and destruction of myelin. 5,6 CNS-resident cells, particularly microglia, pericytes, astrocytes, and CVEs, have the potential to affect the immune response by serving as APCs in the target organ. To serve as an APC, a cell must be able to express the requisite molecules to deliver the 2 signals necessary to activate a T cell. 7 Signal 1 is the antigen-specific signal delivered by antigen in MHC class II binding to the T-cell receptor (TCR). Signal 2, the costimulatory signal, is potently delivered by the B7 family of molecules binding to CD28 on the surface of the T cell. 8 Other costimulatory/adhesion molecules (ie, CD40, CD152, CD106) can deliver or enhance signal 2. 9-11 Professional APCs, such as B lymphocytes, macrophages, and dendritic cells, have been reported to constitutively express MHC class II and B7-1/2. Nonprofessional APCs must up-regulate MHC class II and B7 family members in response to an inflammatory stimulus. The class II transactivator (CIITA), which is absent in the human disease bare-lymphocyte syndrome, 12 has been found to be essential for the inducible and constitutive expression of MHC class II, 13,14 and it is the master switch for MHC class II expression. Moreover, the CIITA has a significant effect on the expression of other proteins associated with class II antigen processing and presentation, including H-2M and invariant chain (Ii). 15 CIITA pr...

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“…In an attempt to study the possible consequences of ␤ cell costimulatory ligand expression, we created and have partially characterized a transgenic mouse expressing murine B7-1 (mCD80) selectively on pancreatic ␤ cells under the rat insulin-1 promoter (RIP) 6 control (10,11). Although these mice rarely develop diabetes spontaneously (Ͻ7% incidence), when disease does occur it has been accompanied by profound insulitis, suggesting an autoimmune pathogenesis (our unpublished observation).…”

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confidence: 99%

Low Dose Streptozotocin-Induced Diabetes in Rat Insulin Promoter-mCD80-Transgenic Mice Is T Cell Autoantigen-Specific and CD28 Dependent

Pechhold

Patterson

Blum

et al. 2001

The Journal of Immunology

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Although transgenic mice expressing murine B7-1 (mCD80) on their pancreatic β cells under the rat insulin-1 promoter (RIP-mCD80+ mice) rarely develop spontaneous β cell destruction and diabetes, we have previously reported the transgene-dependent induction of profound insulitis and lethal diabetes following multiple low dose injections of the β cell toxin streptozotocin (MLDS) in RIP-mCD80+ mice. Here, we have further characterized this MLDS-induced diabetes model using the RIP-mCD80+ mice and now demonstrate that disease is critically dependent on T cell signaling via CD28. Thus, although naive RIP-mCD80+ and nontransgenic littermates have comparable gross β cell mass, and immediately following MLDS induction the mice display similar degrees of insulitis and decrements in the β cell mass, only transgenic mice continued to destroy their β cells and develop insulin-dependent diabetes mellitus. Strikingly, MLDS-induced diabetes was completely prevented in CD28-deficient mice (RIP-mCD80+CD28−/−) due to abrogation of leukocytes infiltrating their pancreatic islets. We further characterized MLDS-induced diabetes in the RIP-mCD80+ mice by demonstrating that the MLDS-induced lymphocytic islet infiltrate contained a substantial frequency of autoantigen-specific, IFN-γ-secreting, CD8+ T cells. We conclude that MLDS-induced β cell destruction and subsequent insulin-dependent diabetes mellitus in RIP-mCD80+ mice is T cell-mediated as it involves both Ag-specific recognition of self-target molecules in the inflamed pancreatic islet (signal 1) and is CD28 costimulation dependent (signal 2).

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CD86 (B70/B7–2) on endothelial cells co-stimulates allogeneic CD4⁺T cells

Cited by 42 publications

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Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Low Dose Streptozotocin-Induced Diabetes in Rat Insulin Promoter-mCD80-Transgenic Mice Is T Cell Autoantigen-Specific and CD28 Dependent

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CD86 (B70/B7–2) on endothelial cells co-stimulates allogeneic CD4+T cells

Cited by 42 publications

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Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Glomerular Endothelium Exhibits Enhanced Expression of Costimulatory Adhesion Molecules, CD80 and CD86, by Warm Ischemia/Reperfusion Injury in Rats

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Low Dose Streptozotocin-Induced Diabetes in Rat Insulin Promoter-mCD80-Transgenic Mice Is T Cell Autoantigen-Specific and CD28 Dependent

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CD86 (B70/B7–2) on endothelial cells co-stimulates allogeneic CD4⁺T cells