• Korean Journal of Transplantation
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• v.31 no.4
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

• Korean Journal of Transplantation
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• v.28 no.3
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• pp.135-143
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• 2014

Background: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. Methods: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. Results: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. Conclusions: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.13 no.2
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• pp.203-216
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• 1991

Nerve allografts as a bridge of regeneration is useful in the repair of peripheral nerve defect resulting from trauma, and leprosy. But immunological rejection and complicated scar formation is an unavoidable problem in the application of allogeneic nerves. This article is intended to study of the regeneration of allogeneic nerve grafts in rats with histopathologically, scanning electron microscopically. 24 adult male Sprague-Dawley rats were used as the experimental animals. A 2cm skin incision was made on the lateral aspects of limb, parallel to femur. Segments of sciatic nerve trunk taken from rats, 10mm was resected at the middle of the thigh, nerve graft was inserted between the ends of gaps with perineural and epineural suture method with 10-0 prolene. Obsrevation was made simultaneously at 3 day, 1, 2, 3, 4, 5, 6, 8 weeks after surgery. The results were as follows. 1. In light and electronic microscopic studies, marked degenerative change of the graft nerves were observed at 2 weeks after surgery. 2. After surgery, blood clot fromation was observed at 3 day, granualtion tissue formation was observed at 2 week, and fibrous tissue proliferation was observed at 3 week. 3. In change of nerve fiber, there were Wallerian degeneration at early stage, decrease in degeneration at 4 week but degeneration of myeline was continuded at 8 week. 4. At 4 week, schwann cells proliferate at its cut ends to join with the distal and proximal stump of the damaged nerve. 5. Fibrous scar tissues are formed at 2 weeks and increased progressively in 8 weeks, which was interrupted the regeneration of grafted nerve.

• Archives of Plastic Surgery
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• v.35 no.4
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• pp.367-372
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• 2008

Purpose: Prevention of acute rejection in skin allografts without continuous immunosuppression lacks reports in worldwide literature. Needs for chronic immunosuppression preclude the use of tissue allograft as a routine surgical reconstructive option. Recently dendritic cells(DC) gained considerable attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effects of alloantigen-pulsed dendritic cells in induction of survival increase in a rat skin allograft model. Methods: Recipient-derived dendritic cells were harvested from rat whole blood and cultured with GM-CSF(200 ng/mL) and IL-4(8 ng/mL) for 2 weeks. Then donor-specific alloantigen pulsed dendritic cells were reinjected into tail vein before skin graft. The rat dorsal skin allografts were transplanted in 5 subgroups. Groups: I) untreated, II) anti-lymphocyte serum(ALS, 0.5 mL), III) FK-506(2 mg/kg), IV) DCp, VI) DCp and FK-506. Graft appearance challenges were assessed postoperatively. Results: The group V(DC and FK-506 treated) showed longest graft survival rate(23.5 days) than other groups; untreated(5.8 days), ALS(7.2 days), FK-506 (17.5 days), DCp(12.2 days). Conclusion: Donor antigen pulsed host dendritic cell combined with short-term immunosuppression prolong skin allograft survival and has potential therapeutic application for induction of donor antigen specific tolerance.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.

• IMMUNE NETWORK
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• v.8 no.4
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• pp.107-123
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• 2008

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.285-285
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• 1996

Cyclosporin A (CyA) is widely used in the inhibition of graft rejection in organ transplantation. However, the bioavailability of CyA after oral administration is very low due to its poor solubility and dispersability hi water. To improve the solubility of CyA, microemulsion systems were developed and its physicochemical characteristics were evaluated by phase studies, solubility and dispersability tests. Phase studies on the systems composed of ethyl oleate (EO), PPG-20 methyl glucose ether (GP-20), poloxamer 123 (PL) and water U) were carried out to make stable w/o emulsions. Besides, based on CyA solubility test in various compositions of surfactant systems, a reasonable surfactant composition (GP-20/PL=4/1) was selected to enhance its solubility.

• Clinical and Experimental Pediatrics
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• v.52 no.10
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• pp.1075-1081
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• 2009

Renal transplantation is the treatment of choice for children with end-stage renal disease. The outcome of pediatric kidney transplantation has improved dramatically in recent years, with lower acute rejection rates, superior graft survival, and low mortality. These improvements have allowed increased attention to other aspects of care for long-term survivors. Taking this into consideration, this review article will focus on the key issues related to pediatric kidney transplantation such as growth, neurocognitive function, nonadherence, and posttransplantation infectious complications, including lymphoproliferative disease, to broaden the understanding of pediatricians who provide pre-and postoperative care to children with end-stage renal disease.

• Journal of Yeungnam Medical Science
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• v.40 no.2
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• pp.115-122
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• 2023

Hepatic ischemia-reperfusion injury is a major complication of liver transplantation, trauma, and shock. This pathological condition can lead to graft dysfunction and rejection in the field of liver transplantation and clinical hepatic dysfunction with increased mortality. Although the pathological mechanisms of hepatic ischemia-reperfusion injury are very complex, and several intermediators and cells are involved in this phenomenon, oxidative stress and inflammatory responses are the key processes that aggravate hepatic injury. This review summarizes the current understanding of oxidative stress and inflammatory responses and, in that respect, addresses the therapeutic approaches to attenuate hepatic ischemia-reperfusion injury.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.36-43
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• 2020

Background: Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation. Methods: Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value: high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, post-transplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups. Results: Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or post-transplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015). Conclusion: High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.