Prolongation of Rat Intestinal Allograft Survival by Administration of Triptolide-Modified Donor Bone Marrow-Derived Dendritic Cells

Chen, T.; Xu, Hao; Wang, H.Q.; Zhao, Ye; Zhu, Chuanlong; Zhang, Y.H.; Ji, Minghui; Hua, Yibing; Wu, Wei

doi:10.1016/j.transproceed.2008.06.056

Cited by 11 publications

(5 citation statements)

References 12 publications

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“…In small animal models, tol-DCs have been used to induce donor-specific non-responsiveness in various tissue allografts, including intestinal [68] , [69] , liver [70] , [71] , [72] , islet [73] and skin transplants [74] , [75] and kidney allografts in rhesus macaques [76] . Tol-DCs may have particular advantages in induction of transplant tolerance towards pancreatic islets.…”

Section: Tolerogenic Dendritic Cells In Clinical Transplantationmentioning

confidence: 99%

Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

2017

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The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the “holy grail” of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases. Whilst various cell types exhibiting a tolerogenic phenotype have been proposed for such a task, tolerogenic dendritic cells (tol-DCs) are exquisitely adapted for antigen presentation and interact with many facets of the immune system: as such, they are attractive candidates for use in strategies for immune intervention. We review here our current understanding of tol-DC mediated induction and maintenance of immunological tolerance. Additionally, we discuss recent in vitro findings from animal models and clinical trials of tol-DC immunotherapy in the setting of transplantation, autoimmunity and allergy which highlight their promising therapeutic potential, and speculate how tol-DC therapy may be developed in the future.

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Section: Tolerogenic Dendritic Cells In Clinical Transplantationmentioning

confidence: 99%

Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

2017

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“…To confirm this, we compared the ability of LPS‐DC and MMC‐DC in stimulating the proliferation of recipient T cells by MLR test. According to the protocols of many previously published articles [30, 39, 40], proliferation of recipient T cells was tested after 72 h of co‐culture. Our results showed that both donor and F1‐derived LPS‐DC and MMC‐DC could stimulate allogeneic T‐cells proliferation.…”

Section: Resultsmentioning

confidence: 99%

Prevention of Acute and Chronic Allograft Rejection by Combinations of Tolerogenic Dendritic Cells

et al. 2011

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It is well known that adoptive transfer of donor‐derived tolerogenic dendritic cells (DC) helps to reduce acute allograft rejection. However, this method cannot effectively prevent grafts from infiltration of inflammatory cells and fibrosis, and thus has minimal effect on chronic allograft rejection. In this study, we used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor (Balb/c)‐derived MMC‐DC could induce hyporesponsiveness of recipient (C57BL/6) T cells in vitro, potentially by inducing T‐cell apoptosis, decreasing IL‐2 and IL‐12 secretion, and increasing regulatory T‐cell numbers and IL‐10 secretion. Furthermore, anti‐CD154 monoclonal antibody (mAb) treatment combined with donor‐derived MMC‐DC prolonged the survival of the allografts in vivo. The mechanisms were similar to those in vitro. Impressively, both acute and chronic rejection were prevented when donor and F1 generation (Balb/c × C57BL/6) derived MMC‐DC were injected together with anti‐CD154 mAb into recipients before heart allotransplantation. In summary, we showed that donor and F1‐derived tolerogenic DC have a synergistic effect on induction and maintenance of T‐cell regulation and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of these two types of DC could inhibit both acute and chronic transplant rejection in mice.

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“…Several methods can be used to produce stable tolDC ex vivo, with limited or no capacity to transdifferentiate into immunogenic DC. Common methods include inhibiting the expression of immune-stimulatory molecules (CD80/CD86 and IL-2)28–30 or stimulating constitutive expression of immunosuppressive molecules such as IL-4, IL-10 and CTLA-4,31–35 through genetic engineering. Also, exposing differentiating DC ex-vivo to drugs such as dexamethasone and vitamin D336 37 or immunosuppressive cytokines such as IL-10 and TGF-β38–40 and lipopolysaccharides41 can be used to produce tolDC.…”

Section: Tolerogenic Cell Typesmentioning

confidence: 99%

Tolerising cellular therapies: what is their promise for autoimmune disease?

Mosanya

Isaacs

2018

Ann Rheum Dis

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The current management of autoimmunity involves the administration of immunosuppressive drugs coupled to symptomatic and functional interventions such as anti-inflammatory therapies and hormone replacement. Given the chronic nature of autoimmunity, however, the ideal therapeutic strategy would be to reinduce self-tolerance before significant tissue damage has accrued. Defects in, or defective regulation of, key immune cells such as regulatory T cells have been documented in several types of human autoimmunity. Consequently, it has been suggested that the administration of ex vivo generated, tolerogenic immune cell populations could provide a tractable therapeutic strategy. Several potentially tolerogenic cellular therapies have been developed in recent years; concurrent advances in cell manufacturing technologies promise scalable, affordable interventions if safety and efficacy can be demonstrated. These therapies include mesenchymal stromal cells, tolerogenic dendritic cells and regulatory T cells. Each has advantages and disadvantages, particularly in terms of the requirement for a bespoke versus an ‘off-the-shelf’ treatment but also their suitability in particular clinical scenarios. In this review, we examine the current evidence for these three types of cellular therapy, in the context of a broader discussion around potential development pathway(s) and their likely future role. A brief overview of preclinical data is followed by a comprehensive discussion of human data.

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Prolongation of Rat Intestinal Allograft Survival by Administration of Triptolide-Modified Donor Bone Marrow-Derived Dendritic Cells

Cited by 11 publications

References 12 publications

Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

Harnessing the properties of dendritic cells in the pursuit of immunological tolerance

Prevention of Acute and Chronic Allograft Rejection by Combinations of Tolerogenic Dendritic Cells

Tolerising cellular therapies: what is their promise for autoimmune disease?

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