• 대한이식학회지
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• 제31권4호
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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.

• 대한이식학회지
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• 제28권3호
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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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• 제13권2호
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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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• 제35권4호
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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.

• 한국임상수의학회지
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• 제26권2호
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• pp.138-143
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• 2009

허혈/재관류 손상은 급성신부전의 주요 원인이며 이식된 신장의 기능지연을 유발하여 거부반응의 발생을 증가시킨다. 본 연구에서는 쥐의 허혈/재관류 손상모델에서 허혈시간에 따른 면역세포의 변화를 평가하였다. 8주령 수컷 SD rat의 좌신을 각각 30, 45, 60분간 허혈/재관류 동안에 우신을 적출 하였고, 대조군은 우신만 적출하였다. 신장기능은 0, 1, 2, 3, 5, 7일에 각각 평가하였으며, 허혈/재관류 후 1일과 7일에 신장조직을 채취하여 면역형광염색(DCs, NK cells, macrophages, B cells, CD4+ and CD8+ T cells)과 H&E 염색을 실시하였다. 허혈 시간이 증가할수록 신장기능이 감소되었으나, 신장 세뇨관괴사와 염증세포의 침윤이 증가하였다. 허혈/재관류 후 신장조직에서 DCs, NK cells, macrophages, CD4+ T cells, CD8+ T cells의 침윤 증가와 재관류 후 7일째 B cells의 침윤이 관찰되었다. 면역세포는 허혈시간 뿐 아니라 재관류 시간이 증가에 따라 뚜렷하게 관찰되었다. 이 결과는 허혈시간이 증가됨에 따라 면역반응이 증가될 수 있으며, 허혈재관류 손상이 비항원성 면역반응을 유도할 수도 있다는 것을 의미한다.

• IMMUNE NETWORK
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• 제8권4호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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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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• 제52권10호
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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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• 제40권2호
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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.

• 한국임상약학회지
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• 제30권1호
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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.