Donor Apoptotic Lymphocyte Transfusion–Induced Liver Allograft Tolerance by Up-Regulation of CD4+CD25+ Regulatory T Cells in Peripheral Blood

Cheng, Jin; Zhou, Lin; Qin, Yi; Wang, Y.; Xie, Haiyang; Feng, Xiao; Zheng, Shusen

doi:10.1016/j.transproceed.2009.05.033

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…Different responses to LR and LRγ transfusions were also apparent in another measure of adaptive immunity: the number of Tregs identified by flow cytometry phenotyping. Several preclinical studies have shown that induction of Tregs by donor‐specific blood transfusion is advantageous for inducing tolerance and preventing graft rejection . In addition, flow cytometry analysis of human PBMCs exposed to RBCs in vitro showed that FoxP3+ Tregs were induced, and this effect was independent of whether the RBCs were LR or underwent prolonged storage .…”

Section: Discussionmentioning

confidence: 99%

“…Several preclinical studies have shown that induction of Tregs by donor-specific blood transfusion is advantageous for inducing tolerance and preventing graft rejection. [14][15][16] In addition, flow cytometry analysis of human PBMCs exposed to RBCs in vitro showed that FoxP3+ Tregs were induced, and this effect was independent of whether the RBCs were LR or underwent prolonged storage. 17 Our data show that when presurgery samples and postsurgery samples are compared, patients in the STD and LR arms showed significant increases of CD4+CD25 high T cells that also expressed FoxP3 or CTLA4.…”

Section: Discussionmentioning

confidence: 99%

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Transfusion‐related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization

et al. 2019

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BACKGROUND: Adverse events following blood transfusion include allosensitization and generalized immunosuppression, collectively referred to as transfusion-related immune modulation. We evaluated the immunological effects of red blood cell (RBC) and platelet transfusions on alloantibody responses and on immunoregulatory cells in nonimmunosuppressed patients undergoing cardiovascular surgery. ABBREVIATIONS: FITC = fluorescein isothiocyanate; HLA = human leukocyte antigen; IFN-γ = interferon-γ; iNKT = invariant natural killer T; LR = leukoreduced; LRγ = leukoreduced and γ-irradiated; MESF = molecules of equivalent soluble fluorochrome; PBMCs = peripheral blood mononuclear cells; STD = standard unmodified; TGF-β1 = transforming growth factor-β1; Tregs = T regulatory lymphocytes; TRIM = transfusion-related immunomodulation.From the 1 Bloodworks Northwest, the

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transfusion‐related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization

et al. 2019

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“…Through directly targeting DCs with allo-antigens, the anti-donor indirect T and B cell responses in allograft recipients were ameliorated. In liver transplantation in rats, donor apoptotic splenic lymphocytes have been shown to promote liver graft acceptance and increase peripheral T regs as well ( 84 , 85 ). Furthermore, in liver transplant rejection, administration of tolerogenic DCs with apoptotic lymphocytes alleviated the rejection while inducing immune tolerance ( 86 ).…”

Section: Apoptotic Cell Therapies In Solid Organ and Tissue Transplanmentioning

confidence: 99%

Apoptotic Donor Cells in Transplantation

Husain

Luo

2021

Front. Immunol.

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Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted organ together with risks for opportunistic infections. Transplantation tolerance has so far only been achieved through hematopoietic chimerism, which carries with it a serious and life-threatening risk of graft versus host disease, along with variability in persistence of chimerism and uncertainty of sustained tolerance. More recently, numerous in vitro and in vivo studies have explored the therapeutic potential of silent clearance of apoptotic cells which have been well known to aid in maintaining peripheral tolerance to self. Apoptotic cells from a donor not only have the ability of down regulating the immune response, but also are a way of providing donor antigens to recipient antigen-presenting-cells that can then promote donor-specific peripheral tolerance. Herein, we review both laboratory and clinical evidence that support the utility of apoptotic cell-based therapies in prevention and treatment of graft versus host disease and transplant rejection along with induction of donor-specific tolerance in solid organ transplantation. We have highlighted the potential limitations and challenges of this apoptotic donor cell-based therapy together with ongoing advancements and attempts made to overcome them.

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“…In LT, tolerance induction using apoptotic cells was studied in rats by two groups. Researchers from Zhejiang University reported that donor apoptotic cells can promote liver graft acceptance using a rat LT model (106). In this study, apoptotic splenic lymphocytes induced by ultraviolet-C (UVC) irradiation at a dosage of 5 × 10 7 cells/rat were infused intravenously at 7 days before LT.…”

Section: Apoptotic Cells For Tolerance Inductionmentioning

confidence: 99%

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

et al. 2020

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Liver transplantation (LT) has become the best chance and a routine practice for patients with end-stage liver disease and small hepatocellular carcinoma. However, lifelong immunosuppressive regimens could lead to many post-LT complications, including cancer recurrence, infections, dysmetabolic syndrome, and renal injury. Impeccable management of immunosuppressive regimens is indispensable to ensure the best long-term prognosis for LT recipients. This is challenging for these patients, who probably have a post-LT graft survival of more than 10 or even 20 years. Approximately 20% of patients after LT could develop spontaneous operational tolerance. They could maintain normal graft function and histology without any immunosuppressive regimens. Operational tolerance after transplantation has been an attractive and ultimate goal in transplant immunology. The liver, as an immunoregulatory organ, generates an immune hyporesponsive microenvironment under physiological conditions. In this regard, LT recipients may be ideal candidates for studies focusing on operative tolerance. Cell-based strategies are one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory T cells, regulatory dendritic cells, regulatory macrophages, regulatory B cells, and mesenchymal stromal cells. The safety and the efficacy of many cell products have been evaluated by prospective clinical trials. In this review, we will summarize the latest perspectives on the clinical application of cell-based strategies in LT and will address a number of concerns and future directions regarding these cell products.

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Donor Apoptotic Lymphocyte Transfusion–Induced Liver Allograft Tolerance by Up-Regulation of CD4+CD25+ Regulatory T Cells in Peripheral Blood

Cited by 5 publications

References 24 publications

Transfusion‐related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization

Transfusion‐related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization

Apoptotic Donor Cells in Transplantation

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

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