Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torrás, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, S.; Grinyó, Josep M.

doi:10.1681/asn.2007111174

Cited by 148 publications

(117 citation statements)

References 30 publications

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“…In multivariate analysis, higher FoxP3 mRNA levels did not correlate with favorable 6-mo graft outcomes, even when the analysis was restricted to biopsies with rejection. Contrary to this study 22 and in agreement with the results of our study, Bestard et al 23 suggest that immunostaining of FoxP3 ϩ Tregs in protocol biopsies seems to be useful for the prediction of long-term kidney transplant outcome. Similarly, in the mouse renal transplant model, the presence of FoxP3 Tregs decreased during ongoing rejection.…”

Section: Discussionsupporting

confidence: 90%

Molecular Phenotypes of Acute Rejection Predict Kidney Graft Prognosis

Viklický

Hřibová²,

Volk³

et al. 2010

Journal of the American Society of Nephrology

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Earlier detection of antibody-mediated rejection of kidney allografts may improve graft outcomes. Profiling of gene expression holds promise for the diagnosis and prognosis of antibody-mediated rejection. Here, we identified 730 patients who received kidney transplants during 2002-2005, including 21 patients (2.9%) who experienced early acute antibody-mediated rejection. We also identified a matched group of 43 patients with early acute T cell-mediated rejection to serve as controls. Compared with patients with T cell-mediated rejection, those with antibody-mediated rejection had significantly higher intrarenal mRNA expression of the cytoprotective heme oxygenase-1 but had lower expression of the regulatory T cell marker forkhead box P3 (FoxP3), the B cell marker CD20, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES). T cell infiltration was similar in both groups of patients. Compared with grafts that had a favorable course, those that failed as a result of antibody-mediated rejection had expression profiles suggesting a lack of regulation (less FoxP3, TGF-␤1, RANTES, and CD20). Grafts that failed as a result of T cell-mediated rejection only revealed lower expression of CD20 mRNA. In summary, these data suggest that severe antibody-mediated rejection and T cell-mediated rejection result in graft loss by distinct mechanisms. Molecular phenotypes of early acute rejection might help to identify grafts with poor prognosis, allowing earlier application of additional therapies.

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Section: Discussionsupporting

confidence: 90%

Molecular Phenotypes of Acute Rejection Predict Kidney Graft Prognosis

Viklický

Hřibová²,

Volk³

et al. 2010

Journal of the American Society of Nephrology

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“…In accordance with previous studies reporting reduced Treg frequencies in solid organ allograft rejection 30 Tregs constitute an attractive therapeutic target given their essential role in controlling autoimmunity. However, recent animal studies provide evidence for functional heterogeneity and lineage plasticity within the Treg compartment.…”

Section: Discussionsupporting

confidence: 88%

A New Immunotherapy Using Regulatory T-Cells for High-Risk Corneal Transplantation

Inomata

2017

Juntendo Medical Journal

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Corneal transplantation is the most commonly performed tissue transplantation worldwide. Despite very high (above 90%) survival rates in recipients with nonvascularized and noninflamed graft beds, survival rates significantly decline (under 50%) when grafts are placed onto vascularized or inflamed host beds associated with conditions such as previous graft rejection, infection, or trauma. These results are seen despite treatment with high doses of nonspecific immunosuppressive medications, which often do not promote long-term survival.Therefore, new strategies are required to modulate the immune system without conventional immunosuppressive agents and improve transplant survival in "high-risk" patients with inflamed host beds. Regulatory T-cells (Treg) are key modulators of the immune response and may play a crucial role in a new therapy for high-risk corneal transplantation.Here we introduce the murine high-risk corneal transplantation model and review the implications of Tregs for corneal transplantation.Key words: corneal transplantation, regulatory T-cell, high-risk corneal transplantation, neovascularization Introduction Outline of corneal transplantationThe first corneal transplantation was successfully performed by Dr. Eduard Zirm in 1905 1) . Along with the growing demand for corneal transplantation, the first institutional eye bank was born in New York in 1944. In Japan, the first eye bank was established by Juntendo University School of Medicine and Keio University in 1963. Nowadays, cornea transplantation is one of the most frequently performed solid organ transplantation worldwide with 65,000 cases annually. There are more than 40,000 cases in the US and 1,500 cases in Japan annually 2) .The cornea is the transparent, dome shaped layer that covers the anterior eye and has the dual function of protecting the inner contents of the eye as well as providing approximately two thirds of the eyeʼs refractive power. The cornea has three layers, including the epithelium, stroma and endothelium, divided by Bowmanʼ s membrane and Descemetʼ s membrane respectively. Corneal transplantation is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue. Corneal transplantation has evolved into an array of techniques focused on the selective replacement of diseased layers of the cornea such as lamellar corneal transplantation, Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty. These procedures are tailored specifically to the underlying pathologic condition causing the corneal dysfunction. However, the majority of corneal transplantations are still penetrating keratoplasties . In all forms of transplantation, certain hosts are known to be at particularly high risk for graft rejection. High-risk transplant recipients often abruptly and irreversibly reject their grafts regardless of the magnitude of immunosuppression. Thus, understanding the underlying mechanisms of high rejection rates in high-risk corneal transportation is essential fo...

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“…Multiple studies have demonstrated that Tregs promote postischemic kidney preconditioning and repair, suppress rejection, and induce allograft tolerance in kidney transplantation. [30][31][32][33] Alternately, DCs and macrophages have been shown to worsen ischemic injury through various mechanisms and depletion of these cells protects the kidney from IR injury. [34][35][36][37][38] Although numbers of DCs and macrophages increased after IR compared with baseline kidneys, their number was low in kidneys of CD4-Keap1-KO mice in this study.…”

Section: Discussionmentioning

confidence: 99%

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

Noel¹,

Martina

Bandapalle³

et al. 2015

Journal of the American Society of Nephrology

100

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T lymphocytes are established mediators of ischemia reperfusion (IR)-induced AKI, but traditional immune principles do not explain their mechanism of early action in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for cytoprotective gene expression and is generally thought to have a key role in dampening IRinduced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis that augmentation of Nrf2 in T cells is essential to mitigate oxidative stress during IR-induced AKI. We therefore generated mice with genetically amplified levels of Nrf2 specifically in T cells and examined the effect on antioxidant gene expression, T cell activation, cytokine production, and IR-induced AKI. T cell-specific augmentation of Nrf2 significantly increased baseline antioxidant gene expression. These mice had a high frequency of intrarenal CD25 increased T cell expression of Nrf2 were significantly protected from functional and histologic consequences of AKI. Furthermore, adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury and significantly improved their survival. These data demonstrate that T cell-specific activation of Nrf2 protects from IR-induced AKI, revealing a novel mechanism of tissue protection during acute injury responses.

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Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

Cited by 148 publications

References 30 publications

Molecular Phenotypes of Acute Rejection Predict Kidney Graft Prognosis

Molecular Phenotypes of Acute Rejection Predict Kidney Graft Prognosis

A New Immunotherapy Using Regulatory T-Cells for High-Risk Corneal Transplantation

T Lymphocyte–Specific Activation of Nrf2 Protects from AKI

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