Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice

Yang, Songfan; Xue, Wujun; Lu, Wan-hong; Xie, Liyi; Yin, Ai-ping; Jian, Zheng; Sun, Jiping; Li, Yang

doi:10.1016/j.trim.2015.08.004

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…Immune tolerance has been clinically applied in organ transplantation. Yang et al found that immune tolerance can be established by transplanting hematopoietic stem cells to reduce the immune response after pancreas transplantation (22). Vanikar et al co-infused mesenchymal stem cells and hematopoietic stem cells for renal transplantation immune tolerance (23).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Surgical Brain Injury by Immune Tolerance Induced by Peripheral Intravenous Injection of Biotargeting Nanoparticles Loaded With Brain Antigens

Tian

Chen

et al. 2019

Front. Immunol.

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Once excessive, neurological disorders associated with inflammatory conditions will inevitably cause secondary inflammatory damage to brain tissue. Immunosuppressive therapy can reduce the inflammatory state, but resulting infections can expose the patient to greater risk. Using specific immune tolerance organs or tissues from the body, brain antigen immune tolerance treatment can create a minimal immune response to the brain antigens that does not excessively affect the body's immunity. However, commonly used immune tolerance treatment approaches, such as those involving the nasal, gastrointestinal mucosa, thymus or liver portal vein injections, affect the clinical conversion of the therapy due to uncertain drug absorption, or inconvenient routes of administration. If hepatic portal intravenous injections of brain antigens could be replaced by normal peripheral venous infusion, the convenience of immune tolerance treatment could certainly be greatly increased. We attempted to encapsulate brain antigens with minimally immunogenic nanomaterials, to control the sizes of nanoparticles within the range of liver Kupffer cell phagocytosis and to coat the antigens with a coating material that had an affinity for liver cells. We injected these liver drug-loaded nanomaterials via peripheral intravenous injection. With the use of microparticles with liver characteristics, the brain antigens were transported into the liver out of the detection of immune armies in the blood. This approach has been demonstrated in rat models of surgical brain injury. It has been proven that the immune tolerance of brain antigens can be accomplished by peripheral intravenous infusion to achieve the effect of treating brain trauma after operations, which simplifies the clinical operation and could elicit substantial improvements in the future.

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Section: Discussionmentioning

confidence: 99%

Treatment of Surgical Brain Injury by Immune Tolerance Induced by Peripheral Intravenous Injection of Biotargeting Nanoparticles Loaded With Brain Antigens

Tian

Chen

et al. 2019

Front. Immunol.

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“…Yang et al. reported that syngeneic HSC transfer into sub‐lethally irradiated mice causes expansion of Treg cells, and results in prolonged survival of a pancreatic‐islet allograft . Likewise, not only HSCs but also BM‐derived mesenchymal stem cells reportedly generated Treg cells .…”

Section: Discussionmentioning

confidence: 99%

Donor bone marrow cells are essential for iNKT cell‐mediated Foxp3+ Treg cell expansion in a murine model of transplantation tolerance

et al. 2017

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Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera. However, the mechanism of expansion and bioactivity of Treg cells remains unclear. Here, we examine the role of donor BMCs in the expansion of bioactive Treg cells. The mouse model was transplanted with a heart allograft the day after treatment. The results showed that transfer of spleen cells in place of BMCs failed to deplete host interferon (IFN)-γ-producing CD8 T cells, expand host Ki67 CD4 CD25 Foxp3 Treg cells, and prolong graft survival. Severe combined immunodeficiency mice who received Treg cells obtained from BMC-recipients accepted skin grafts in an allo-specific manner. Myeloid-derived suppressor cells, which were a copious cell subset in BMCs, enhanced the Ki67 expression of Treg cells. This suggests that donor BMCs are indispensable for the expansion of host bioactive Treg cells in our novel treatment for transplant tolerance induction.

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“…CD4 + T cells classically differentiate into two subgroups: pro-inflammatory Th1 cells and anti-inflammatory Th2 cells19. Th1 cells mainly secrete IL-2 and IFN-γ, whereas Th2 cells mainly secrete IL-4 and IL-520. Cytokines are necessary regulators for lymphocyte trafficking.…”

Section: Discussionmentioning

confidence: 99%

Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

Yang

Liu

et al. 2016

Sci Rep

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Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4+T/CD8+T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections.

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Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice

Cited by 7 publications

References 40 publications

Treatment of Surgical Brain Injury by Immune Tolerance Induced by Peripheral Intravenous Injection of Biotargeting Nanoparticles Loaded With Brain Antigens

Treatment of Surgical Brain Injury by Immune Tolerance Induced by Peripheral Intravenous Injection of Biotargeting Nanoparticles Loaded With Brain Antigens

Donor bone marrow cells are essential for iNKT cell‐mediated Foxp3+ Treg cell expansion in a murine model of transplantation tolerance

Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

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