DONOR ANTIGENIC SPECIFICITY CD4+CD25+TREG CELLS INDUCE IMMUNE TOLERANCE OF ALLOGRAFT KIDNEY TRANSPLANTATION IN RATS

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 484
Author(s):  
S Gu ◽  
C Huang ◽  
J Zheng ◽  
Y Zhang ◽  
J Li ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Immune Tolerance ◽  
Treg Cells ◽  
Antigenic Specificity ◽  
Allograft Kidney

scholarly journals Exosomes Secreted by Mesenchymal Stem Cells Induce Immune Tolerance to Kidney Transplantation via Transporting lncRNA DANCR

2021 ◽  
Author(s):  
Xiaoqiang Wu ◽  
Zhiwei Wang ◽  
Junpeng Wang ◽  
Xiangyong Tian ◽  
Guanghui Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Kidney Transplantation ◽  
Cell Differentiation ◽  
Inflammatory Response ◽  
Treg Cell ◽  
Immune Tolerance ◽  
Treg Cells ◽  
Related Factors ◽  
T Cell Infiltration

Abstract BackgroundMesenchymal stem cells induce kidney transplant tolerance by increasing regulatory T (Treg) cells. Bone marrow mesenchymal stem cell exosomes (BMMSC-Ex) promote Treg cell differentiation. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is expressed in BMMSCs and can be encapsulated in exosomes. We aimed to explore the role of DANCR in BMMSC-Ex in immune tolerance after kidney transplantation and related mechanism.MethodsThe kidney transplantation model was established and levels of serum creatinine (SCr) were determined. Hematoxylin-eosin staining was conducted to detect the inflammation and immunohistochemistry was performed to detect the infiltration of CD4+ T cells. Levels of IFN-γ, IL-17 and IL-2 were examined by ELISA. Flow cytometry was conducted to determine Treg cells.ResultsIn allograft group, the inflammatory response was severe, CD4+ T cell infiltration, SCr levels, and plasma rejection related factors were up-regulated, while injection of BMMSC-Ex reversed the results. BMMSC-Ex increased Treg cells in kidney transplantation mice. Interference with DANCR reversed the promoting effect of BMMSC-Ex on Treg cell differentiation. DANCR bound to SIRT1, promoted ubiquitination and accelerated its degradation. The injection of BMMSC-Ex (after interference with DANCR) promoted SIRT1 levels, inflammatory response, CD4+ T cell infiltration, SCr levels, and plasma rejection related factors′ expression, while Treg cells were decreased.ConclusionLncRNA DANCR in BMMSC-Ex promoted Treg cell differentiation and induced immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4+ T cells.

Laparoscopic kidney transplantation with transvaginal insertion of allograft kidney

2018 ◽  
Vol 17 (4) ◽  
pp. e2156
Author(s):  
E. Özden ◽  
Y.K. Yakupoglu ◽  
S. Oner ◽  
M. Ozen ◽  
M. Gulsen ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Allograft Kidney

scholarly journals Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment

2020 ◽  
Vol 29 ◽  
pp. 096368972091387 ◽  
Author(s):  
Seok-Joo Lee ◽  
Hyun-Je Kim ◽  
Na-ri Byun ◽  
Chung-Gyu Park
Keyword(s):  
Islet Transplantation ◽  
Immune Tolerance ◽  
Treg Cells ◽  
Transplantation Tolerance ◽  
Single Treatment ◽  
Short Term ◽  
Donor Skin ◽  
First Time ◽  
Mixed Lymphocyte Reactions ◽  
Transplantation Model

Anti-CD154 blockade-based regimens remain unequaled in prolonging graft survival in various organ transplantation models. Several studies have focused on transplantation tolerance with the anti-CD154 blockade, but none of these studies has investigated the mechanisms associated with its use as the sole treatment in animal models, delaying our understanding of anti-CD154 blockade-mediated immune tolerance. The purpose of this study was to investigate the mechanism underlying the anti-CD154 monoclonal antibody (mAb) blockade in inducing immune tolerance using an intrahepatic murine allogeneic islet transplantation model. Allogeneic BALB/c AnHsd (BALB/c) islets were infused into the liver of diabetic C57BL/6 (B6) mice via the cecal vein. Anti-CD154 mAb (MR1) was administered on −1, 0, 1, 3, 5, and 7 d posttransplantation at 0.5 mg per mouse. We showed that short-term MR1 monotherapy could prolong the allogeneic islet grafts to more than 250 d in the murine intrahepatic islet transplantation model. The second islet grafts transplanted under the kidney capsule of the recipients were protected from rejection. We also found that rejection of same-donor skin grafts transplanted to the tolerant mice was modestly delayed. Using a DEREG mouse model, FoxP3+ regulatory T (Treg) cells were shown to play important roles in transplantation tolerance. In mixed lymphocyte reactions, Treg cells from the tolerant mice showed more potency in suppressing BALB/c splenocyte-stimulated Teff cell proliferation than those from naïve mice. In this study, we demonstrated for the first time that a short-term anti-CD154 mAb single treatment could induce FoxP3+ Treg cell-mediated immune tolerance in the intrahepatic murine allogeneic islet transplantation model.

scholarly journals Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

2021 ◽  
Vol 10 (1) ◽  
pp. 204-214
Author(s):  
Tianying Yang ◽  
Jiawei Li ◽  
Yichen Jia ◽  
Chunchen Yang ◽  
Ruirui Sang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Immune Tolerance ◽  
Suppressor Cell ◽  
Myeloid Derived Suppressor Cell ◽  
Key Genes

scholarly journals Endocrine Disruptor Compounds—A Cause of Impaired Immune Tolerance Driving Inflammatory Disorders of Pregnancy?

2021 ◽  
Vol 12 ◽  
Author(s):  
John E. Schjenken ◽  
Ella S. Green ◽  
Tenuis S. Overduin ◽  
Chui Yan Mah ◽  
Darryl L. Russell ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Fetal Development ◽  
Inflammatory Responses ◽  
Animal Health ◽  
Embryo Implantation ◽  
Animal Experiments ◽  
Reproductive Function ◽  
Endocrine Disrupting Compounds ◽  
Epidemiological Studies ◽  
Treg Cells

Endocrine disrupting compounds (EDCs) are prevalent and ubiquitous in our environment and have substantial potential to compromise human and animal health. Amongst the chronic health conditions associated with EDC exposure, dysregulation of reproductive function in both females and males is prominent. Human epidemiological studies demonstrate links between EDC exposure and infertility, as well as gestational disorders including miscarriage, fetal growth restriction, preeclampsia, and preterm birth. Animal experiments show EDCs administered during gestation, or to either parent prior to conception, can interfere with gamete quality, embryo implantation, and placental and fetal development, with consequences for offspring viability and health. It has been presumed that EDCs operate principally through disrupting hormone-regulated events in reproduction and fetal development, but EDC effects on maternal immune receptivity to pregnancy are also implicated. EDCs can modulate both the innate and adaptive arms of the immune system, to alter inflammatory responses, and interfere with generation of regulatory T (Treg) cells that are critical for pregnancy tolerance. Effects of EDCs on immune cells are complex and likely exerted by both steroid hormone-dependent and hormone-independent pathways. Thus, to better understand how EDCs impact reproduction and pregnancy, it is imperative to consider how immune-mediated mechanisms are affected by EDCs. This review will describe evidence that several EDCs modify elements of the immune response relevant to pregnancy, and will discuss the potential for EDCs to disrupt immune tolerance required for robust placentation and optimal fetal development.

scholarly journals Low-dose chidamide restores immune tolerance in ITP in mice and humans

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 730-742 ◽  
Author(s):  
Hong-yu Zhao ◽  
Ya-hui Ma ◽  
Da-qi Li ◽  
Tao Sun ◽  
Li-zhen Li ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Histone Deacetylase Inhibitors ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Peripheral Blood Mononuclear ◽  
In Vivo Experiments ◽  
Macrophage Phagocytosis

Abstract Increased macrophage phagocytosis of antibody-coated platelets, as well as decreased numbers and/or impaired function of CD4+CD25+Foxp3+ regulatory T (Treg) cells, has been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Low-dose histone deacetylase inhibitors (HDACi’s) are anti-inflammatory and immunomodulatory agents that can enhance immunosuppression in graft-versus-host disease by increasing the number and function of Foxp3+ Treg cells, but it is unclear whether they have the potential to promote immune tolerance and platelet release in ITP. In this study, we performed in vitro and in vivo experiments and found that a low-dose HDACi (chidamide) alleviated thrombocytopenia in passive and active murine models of ITP. Further, low-dose HDACi’s attenuated macrophage phagocytosis of antibody-coated platelets, stimulated the production of natural Foxp3+ Treg cells, promoted the peripheral conversion of T cells into Treg cells, and restored Treg cell suppression in vivo and in vitro. Finally, we confirmed that low-dose HDACi’s could regulate CTLA4 expression in peripheral blood mononuclear cells through modulation of histone H3K27 acetylation. Low-dose HDACi treatment in ITP could be offset by blocking the effect of CTLA4. Therefore, we propose that low-dose chidamide administration has potential as a novel treatment for ITP in the clinic.

scholarly journals Profiling the Resident and Infiltrating Monocyte/Macrophages during Rejection following Kidney Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jie Wang ◽  
Peiling Luo ◽  
Jingjie Zhao ◽  
Junhua Tan ◽  
Feifan Huang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Immune Tolerance ◽  
Immune Rejection ◽  
Healthy Human ◽  
Rna Analysis ◽  
Biopsy Specimens ◽  
Transplantation Rejection ◽  
Human Adults ◽  
Onset Phase ◽  
Differential Genes

Immune tolerance research is essential for kidney transplantation. Other than antibody and T cell-mediated immune rejection, macrophage-mediated innate immunity plays an important role in the onset phase of transplantation rejection. However, due to the complexity of the kidney environment as well as its diversity and low abundance, studies pertaining to monocyte/macrophages in kidney transplantation require further elucidation. In this study, kidney samples taken from healthy human adults and biopsy specimens from patients undergoing rejection following kidney transplantation were analysed and studied. By conducting a single-cell RNA analysis, the type and status of monocyte/macrophages in kidney transplantation were described, in which monocyte/macrophages were observed to form two different subpopulations: resident and infiltrating monocyte/macrophages. Furthermore, previously defined genes were mapped to all monocyte/macrophage types in the kidney and enriched the differential genes of the two main subpopulations using gene expression databases. Considering that various cases of rejection may be of the monocyte/macrophage type, the present data may serve as a reference for studies regarding immune tolerance following kidney transplantation.

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