• Journal of Veterinary Clinics
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• v.28 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.23 no.1
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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.

• Korean Journal of Veterinary Research
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• v.34 no.2
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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.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.196-202
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• 1999

The purpose of the study was to determine the effect of vitamin B complex on stress-induced immune alteration. 21 medical students participated in the study 4 weeks before an academic examination period(baseline), 2 weeks before the exam period and during the exam period. Among them, 10 subjects were given vitamin B complex for 4 weeks, and 11 were not given vitamin B during the whole period. Cell-mediated immune function was measured by lymphocyte proliferative response to phytohemagglutinin(PHA) and interleukin-2(IL-2) production. Global assessment of recent stress(GARS) scale and symptom checklist-90-revised(SCL-90-R) were used to measure the level of subjective stress and psychopathology. Vitamin group had significantly lower scores of anxiety scale on SCL-90-R than non-vitamin group. No significant differences were found in lymphocyte proliferative response to PHA and IL-2 production between vitamin and non-vitamin groups during each period. There were no significant differences in change of of each of the two immune parameters over time as well as between vitamin and non-vitamin groups. However, lymphocyte proliferative response to PHA was significantly increased over time. In conclusion, it was suggested that vitamin B complex is likely to decrease anxiety level, and that exam stress might enhance lymphocyte proliferation regardless of vitamin B.

• Biomolecules & Therapeutics
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• v.16 no.2
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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.

• Biomedical Science Letters
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• v.1 no.1
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• pp.45-54
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• 1995

The effect of different fatty acids supplementation on antobody production of Salmonella typhi was studied in ICR mice. Subjects supplemented their diets with $50\mu$g of extracted pig oil(as a saturated fatty acid) and fish oil (as a unsaturated fatty acid) / 2 days for 8 weeks. Blood was collected control and experimental groups of mice after 8 weeks of oil supplementation. The different fatty acids supplementation reduced unsaturated fatty acids composition in mice liver such as $C_{18:3}, \; C_{20:3}\; and\; C_{20:4}\; except\; C_{18:1}\; and\; C_{18:2}/C_{18:0}$ in fish oil and pig oil groups compared to control group. Also, the phagocytic activities of mice macrophages for Candida albicans was reduced by 6% in pig oil group and 9％ in fish oil group than control group. The antigen-stmulated lympocite proliferative response was significantly increased by fatty acid in pig oil group(48％) but 57％ in fish oil group. The different fatty acid supplementation increased antibody production in both experimental groups than control group ; this increase was only significant in pig oil group(1:$2^4$) on mice but not in fish oil group(1:$2^0$) compared to control group(1:$2^0$), however, increased antibody titer in both groups in vitro spleen cell culture supernatant(1:$2^3$ in fish oil group and 1:$2^2$ in pig oil group compared to control group 1:$2^0$). Thus, fish oil supplementation was immunosuppresive agent in macrophage phagocytosis, in-vivo antobody producibilities and lympocyte proliferation but pig oil supplementation was more effective than fish oil in antibody formation in-vivo. We find that antibody producibilities affected by fed on different fatty acids were considered by balance between saturated and unsaturated fatty acid, and $C_{20:3}/C_{20:4}$ ratio. Also, it affected to antigen-stimulated lymphocyte proliferation and macrophage phagocytic activities.

• IMMUNE NETWORK
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• v.23 no.4
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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.

• Korean Journal of Medicinal Crop Science
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• v.10 no.5
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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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• v.17
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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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• v.21 no.12
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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.