PD‐1/B7‐H1 Interaction Contribute to the Spontaneous Acceptance of Mouse Liver Allograft

Morita, Miwa; Fujino, Masayuki; Jiang, Guoping; Kitazawa, Yoshiaki; Xie, Lin; Azuma, Miyuki; Yagita, Hideo; Nagao, Shizuko; Sugioka, Atsushi; Kurosawa, Yoshikazu; Takahara, Shiro; Fung, John J.; Shen, Qian; Lü, Lina; Li, Xiaokang

doi:10.1111/j.1600-6143.2009.02859.x

Cited by 107 publications

(110 citation statements)

References 19 publications

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“…Nonhematopoietic PDL1 expression has been reported to be of key importance in murine autoimmune diabetes, in which pancreatic islet cells lacking PDL1 led to earlier onset diabetes associated with significant CD4 + T-cell infiltration and activation (4) and endothelial PDL1 expression was shown to protect the myocardium against T-lymphocyte-induced myocarditis (13). Furthermore, PDL1 expression on sinusoidal endothelial cells and Kupffer cells are known to be essential for liver transplant spontaneous tolerance (14). Our studies show for the first time that PDL1 expression by the endothelium is required to achieve cardiac allograft tolerance in a fully allogeneic mismatched model.…”

Section: Pdl1 Of Donor Endothelium In Allograft Tolerance Similar Surmentioning

confidence: 99%

Essential Role of PDL1 Expression on Nonhematopoietic Donor Cells in Acquired Tolerance to Vascularized Cardiac Allografts

Riella

Watanabe

Sage

et al. 2011

American Journal of Transplantation

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The PD1:PDL1 pathway is an essential negative costimulatory pathway that plays a key role in regulating the alloimune response. PDL1 is expressed not only on antigen-presenting cells (APCs) but also cardiac endothelium. In this study, we investigated the importance of PDL1 expression on donor cardiac allograft in acquired transplantation tolerance in a fully MHC-mismatched model. We generated PDL1 chimeric mice on B6 background that expressed PDL1 on either hematopoietic cells or nonhematopoietic cells of the heart. Sham animals were used as controls. These hearts were then transplanted into BALB/c recipients and treated with CTLA4-Ig to induce tolerance. Cardiac endothelium showed significant expression of PDL1, which was upregulated upon transplantation. While the absence of PDL1 on hematopoietic cells of the heart resulted in delayed rejection and prevented longterm tolerance in most but not all recipients, we observed an accelerated and early graft rejection of all donor allografts that lacked PDL1 on the endothelium. Moreover, PDL1-deficient endothelium hearts had significant higher frequency of IFN-c -producing alloreactive cells as well as higher frequency of CD8 + effector T cells. These findings demonstrate that PDL1 expression mainly on donor endothelium is functionally important in a fully allogeneic mismatched model for the induction of cardiac allograft tolerance.

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Section: Pdl1 Of Donor Endothelium In Allograft Tolerance Similar Surmentioning

confidence: 99%

Essential Role of PDL1 Expression on Nonhematopoietic Donor Cells in Acquired Tolerance to Vascularized Cardiac Allografts

Riella

Watanabe

Sage

et al. 2011

American Journal of Transplantation

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“…The fold change vs one sample of the control group was calculated as described previously. 13 Oxidative Damage Measurement The oxidative stress marker 8-hydroxydeoxyguanosine was measured with an enzyme-linked immunosorbent assay kit (Japan Institute for the Control of Aging, Shizuoka, Japan), according to the manufacturer's instructions. 8-OHdG, a product of oxidatively damaged DNA, was detected using a competitive enzyme-linked immunosorbent assay using a monoclonal antibody (clone N45.1) that is specific for DNA damage.…”

Section: Rna Isolation and Quantitative Real-time Rt-pcrmentioning

confidence: 99%

High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation

Abe

Yazawa

Fujino

et al. 2017

Laboratory Investigation

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Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation (KTx) and frequently influences both short-and long-term allograft survival. Carbon monoxide (CO) has attracted attention as a medical gas with anti-inflammatory and anti-apoptotic effects. We investigated a new strategy for organ preservation using ex vivo application of high-pressure CO in an experimental rat KTx model. We preserved kidney grafts using a high-pressure chamber filled with mixed gases composed of CO and O 2 . We found that cold I/R injury resulted in progressive deterioration of renal graft function in University of Wisconsin solution, whereas CO significantly improved renal function. We confirmed that CO decreased oxidative stress and mRNA expression of proinflammatory cytokines and inhibited tubular apoptosis in the early phases. Western blot analysis demonstrated that CO increased phosphatidylinositol-3 kinase and phosphorylation of Akt and p38 mitogen-activated protein kinase. Furthermore, CO significantly alleviated tubular injury scores and suppressed the development of interstitial fibrosis at 100 days after KTx. Thus, high-pressure mixed CO and O 2 gases successfully preserved rat kidney grafts for 24 h by protecting tubular epithelial cells from apoptosis and inhibiting inflammation.

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“…However, various experimental animal studies showed enhanced rejection and/or decreased graft survival after blockade of coinhibitory receptors in organ-transplanted mice. This implies that coinhibitory receptors are involved in suppressing allograft rejection in mice (23)(24)(25)(26). However, the role of T cell exhaustion and coinhibitory receptor-ligand interactions in human solid organ transplantation have not been widely studied (25).…”

mentioning

confidence: 99%

Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen

Mare-Bredemeijer

Shi

Mancham

et al. 2015

The Journal of Immunology

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The chronic presence of viral Ags can induce T cell exhaustion, which is characterized by upregulation of coinhibitory receptors and loss of T cell function. We studied whether a similar phenomenon occurs after liver transplantation (LTx), when there is continuous exposure to alloantigen. Expression of coinhibitory receptors on circulating CD4+ and CD8+ T cells was analyzed longitudinally in 19 patients until 6 mo after LTx and cross-sectionally in 38 patients late (1–12 y) after LTx. Expression of the coinhibitory receptors CD160 and CD244 on circulating CD8+ T cells was already higher 6 mo after LTx compared with pre-LTx, and the elevated expression was sustained late after LTx, with CD244 showing the more prominent increase. The strongest upregulation of CD244 on circulating CD8+ T cells was observed in patients who experienced CMV infection after LTx. CMV infection also was associated with reduced CD8+ T cell proliferation and cytotoxic degranulation in response to alloantigen late after LTx. Purified CD244+CD8+ T cells from LTx patients showed lower proliferative responses to alloantigen, as well as to polyclonal stimulation, than did their CD244− counterparts. In addition, the CD244+CD8+ T cell population contained the majority of CMV peptide–loaded MHC class I tetramer-binding cells. In conclusion, CMV infection after LTx, rather than persistence of alloantigen, induces the accumulation of dysfunctional CD244+CD8+ T cells in the circulation that persist long-term, resulting in reduced frequencies of circulating alloreactive CD8+ T cells. These results suggest that CMV infection restrains CD8+ T cell alloresponses after LTx.

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PD‐1/B7‐H1 Interaction Contribute to the Spontaneous Acceptance of Mouse Liver Allograft

Cited by 107 publications

References 19 publications

Essential Role of PDL1 Expression on Nonhematopoietic Donor Cells in Acquired Tolerance to Vascularized Cardiac Allografts

Essential Role of PDL1 Expression on Nonhematopoietic Donor Cells in Acquired Tolerance to Vascularized Cardiac Allografts

High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation

Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen

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