• 한국임상수의학회지
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• 제28권4호
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• pp.399-402
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• 2011

In recent years, the mesenchymal stem cells (MSC) derived from various tissues have been widely tested for developing cell therapies, tissue repair and transplantation. Although there has been much interest in the immunomodulatory properties of MSC and their immunologic reactions following autologous, allogeneic and xenogenic transplantation of MSC in vivo, up to date, the expression of immunogenic markers, such as class I and II human leukocyte antigens (HLA), after differentiation of human umbilical cord blood (hUCB)-derived MSC has been poorly investigated and require extensive in vitro and in vivo testing. In this experiment, the expression of the HLA-ABC and HLA-DR on hUCB-derived MSC have been tested by immunocytochemical staining. The undifferentiated MSC were moderately stained for HLA-ABC but very weakly for HLA-DR. In order to investigate the inhibitory effect of allogeneic lymphocytes on proliferation of MSC, the MSC were cultured in the presence or absence of peripheral allogeneic lymphocytes stimulated with concanavalin A. The allogeneic lymphocytes did not significantly inhibit MSC proliferation. We conclude that hUCB-MSC expressed moderately class I HLA antigen while almost negatively class II HLA antigen. The MSC have an immunomodulatory effect which can suppress the allogeneic response of lymphocytes. These in vitro data suggest that allogeneic MSC derived from cord blood can be useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.

• 대한한방내과학회지
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• 제23권1호
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• pp.123-131
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• 2002

Objective : It is well known that modern chemotherapy against cancer has side effects to a living body, especially hemopoietic and immunologial disfunctions. However, there are no effective ways to reduce them. Recently, traditional Korean herb medicine has been reported to have some biological modifying responses. Therefore, we hypothesized that additional application of herb medicine during chemotherapy is more effective to reduce its side effects. While we were studying the effects, we have observed the inhibitory effect of Soamgudamikgitang on formation of side effects derived from Cyclophosphamide, it has been used in clinical practice at Kyung Hee Medical Center. Methods : We injected 200mg/kg of Cyclophosphamide, one time, to an experimental group, consisting of ten mice. We divided them into eight groups: normal, CPX, SAKT 2mg, SAKT 10mg, SAKT 50mg, SAKT 2mg, CPX, SAKT 10mg+CPX, SAKT 50mg+CPX. We injected Soamgudamikgitang seven days, five days, three days, and one day before we injected CPX. One day, three days, and five days after CPX injection, we injected Soamgudamikgitang again and then killed all the mice. The parameters determined in this experiment were daily body weight liver and spleen weight, RBC, WBC, and platelet for hemopoietic dysfunction and AST, ALT for hepatotoxicity, BUN, creatine for renal toxcity, lymphocyte proliferation activity and lymphocyte subsets for immunological toxcity. Results : We have found that Soamgudamikgitang has inhibitory effects on the formation of Cyclophosphamide's side effects. Significant differences between the group, which contained Cyclophosphamide, and the other group, which contains Cyclophosphamide and 2, 10, 50mg of Soamgudamikgitang respectively were observed. Platelets(2mg of Soamgudamikgitang, p<0.05 ;10mg, p<0.01 ;50mg, p<0.001), liver weight(50mg, p<0.01), spleen weight(10mg, p<0.05), AST(all groups, p<0.01), ALT(2mg, p<0.01 ;10mg, p<0.05 ;50mg, p<0.01), BUN(2mg, p<0.01 ;50mg, p<0.05). Although immunological in both lymphocyte proliferation and its subsets were not observed, which shows that Soamgudamikgitang has a strong effect on T cell activities. Conclusions : From the above results, we can expect that the combined therapy of Soamgudamikgitang and Cyclophosphamide is more effective for treating cancer patients.

• 대한수의학회지
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• 제34권2호
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• 정신신체의학
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• 제7권2호
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• pp.196-202
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• 1999

본 연구의 목적은 비타민 B복합제가 스트레스에 의해 유도된 변역변화에 대한 효과를 알아보기 위해 조사되었다. 대상은 의과대학 학생들로 시험 4주전, 시험 2주전, 시험기간 세 차례를 모두 완료한 21 명으로 하였다. 이들 중 10명은 비타민 투여군으로, 11명은 비투여군으로 구분하였다. 스트레스지각 및 정신병리를 평가하기 위해 global assessment of recent stress(GARS) 척도와 symptom checklist-90-revised(SCL-90-R)를 사용하였다. 세포성 면역기능은 phytohemagglutinin(PHA)에 대한 임파구 증식반응 및 interleukin-2(IL-2)생성능을 측정하여 평가하였다. 비타민투여군이 비투여군에 비해 SCL-90-R상 불안척도의 점수가 유의하게 낮았다. 그러나 비타민 B 투여유무에 따른 임파구증식반응 및 IL-2생성능은 유의한 차이를 보이지 않았다, 시간경과에 따른 임파구증식반응은 유의하게 증가되었다. 시간 경과 및 비타민 투여유무에 따른 임파구증식반응 및 IL-2생성능의 변화량은 각각 유의한 차이를 보이지 않았다. 결론적으로 비타민 B복합제는 불안을 경감시키나 세포성 면역기능에는 유의한 영향을 미치지 않음을 시사한다. 한편 시험스트레스는 비타민 B 투여에 관계없이 임파구증식반응을 증가시킬 가능성이 시사되었다.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• 대한의생명과학회지
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• 제1권1호
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• pp.45-54
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• 1995

지방산 식이가 항체 생성력에 미치는 영향을 알아보기 위하여 ICR계 마우스를 기본사료만 투여한 대조군, 돈유 투여군, 그리고 정어리유 투여군으로 나눈 다음, 추출한 지방산을 8주동안 경구 투여한 후, 마우스 간조직 중의 지방산 조성 변화, Salmonella typhi에 대한 항체 역가, 복강내 대식세포의 탐식능 및 비장세포의 증식능을 비교 관찰한 결과는 다음과 같다. 대조군에 비하여 돈유 투여군에서는 $C_{18:3}$, $C_{20:3}$, $C_{20:4}$ 등의 지방산이 감소하였고, 정어리 투여군에서는 $C_{18:1}$, $C_{18:2}$, $C_{18:0}$를 제외한 주요 불포화 지방산 성분이 감소되었다. 대식세포의 탐식능에서는 대조군에 비하여 실험군의 대식세포 탐식능이 저하되었고, 마우스 생체 항체 생성력은 돈유 투여군이 대조군 및 정어리유 투여군보다 높은 역가를 나타내었으며, 마우스 비장세포 배양 상층액 중의 항체 역가는 마우스 생체 역가와는 다르게 정어리유 투여군이 더 높은 역가는 나타내었다. 또한 비장세포 증식능은 증시능을 나타내었다. 이러한 차이는 포화, 불포화 지방산 균형 증가에 의하여 면역 억제력이 높아진 결과로 생각되며, 포화 지방산의 투여는 항체 생성력을 현저하게 증가시킬 수는 있으나 면역 억제력은 타나내지 못함을 알 수 있었다.

• IMMUNE NETWORK
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• 제23권4호
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• 한국약용작물학회지
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• 제10권5호
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• pp.327-332
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• 2002

This study was conducted to investigate the immuno-regulatory effect and apoptosis of L1210 and HL60 leukemia cells of methanol-extracts of Cornus kousa Burg(CKB). The proliferation of mouse splenocytes and thymocytes enhanced by the addition of $10\;{\mu}g/ml$ of CKB. CKB were administered p.o. once a day for 7 days in adult male BALB/c mice. CKB increased the splenic and thymic T lymphocytes, especially the number of $T_H$ cells markedly increased by the treatment of CKB. CKB treatment induced the apoptotic cell death in L1210 mouse leukemia and HL60 human leukemia cells. In addition, CKB also accelerated the phagocytic activity in peritoneal macrophages and increased the production of plaque forming cells. These results suggest that CKB have an various immuno-regulatory property.

• Toxicological Research
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• 제17권
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• pp.217-218
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• 2001

In a series of our screening for immunomodulating substances, we isolated prodigiosin from the culture broth qf Serratia marcescens B-1231. This compound inhibited the T cell-mediated immune responses such as concanavalin A-induced proliferation, mixed lymphocyte response, local graft versus host reaction and T-dependent antibody response at nontoxic concentrations. However. prodigiosin did not effect B cell-mediated immune functions such as lipopolysaccharide-induced proliferation and -activated polyclonal antibody production at the same concentrations. Prodigiosin did not cause death in vitro to lymphocytes at effective concentrations (＜100 nM) and also did not show toxicity in vivo to lymphoid organs at effective dos-ages (10 and 30 mg/kg). The pharmacological potencies were comparable to the activities of well-known T-cell specific immunosuppressants such as cyclosporin A. In our continuing study, mechanism of action of PDG is investigated with respect to the effect of PDG on IL-2/IL-2R pathway and transcription factor.

• Journal of Microbiology and Biotechnology
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• 제21권12호
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• pp.1264-1269
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• 2011

Interleukin-2 (IL-2) is a vital cytokine secreted by activated T lymphocytes, and plays an important role in the regulation of cellular functions and immunity of animals. In this study, the recombinant duck IL-2 (rduIL-2) was secretory expressed in Pichia pastoris (P. pastoris). The recombinant P. pastoris strain was cultured in shake flasks and then scaled up in a 5.0-l bioreactor. The result showed that the maximal fresh-cell-weight of 594.1 g/l and the maximal $OD_{600}$ of 408 were achieved in the bioreactor. The rduIL-2 was purified by two steps of purification procedures, and approximately 311 mg of rduIL-2/L fermentation supernatant was obtained. SDS-PAGE showed that the purified rduIL-2 constituted a homogeneous band of ~16 kDa or ~14 kDa corresponding to the glycosylated or non-glycosylated duIL-2 protein in size, respectively. The bioactivity of rduIL-2 was determined by lymphocyte proliferation assay. The result indicated that the rduIL-2 greatly promoted the proliferation of ConA-stimulated lymphocytes in vitro. The P. pastoris expression system described here could provide promising, inexpensive, and large-scale production of the rduIL-2, which lays the foundation for development of novel immunoadjuvants to enhance both the immunity of ducks against various infectious pathogens and vaccine efficacy.