• The Journal of Korean Medicine
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• v.23 no.2
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• pp.211-224
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• 2002

Background and Objective : In order to investigate the effects of Gilgyunglwedok-tang (GRT) on antitumor activity and antimetastatic activity, studies were done experimentally. Materials and Methods : Experimental studies were perfonned for the cytotoxic effect on BALB/c mouse lung fibroblast cells, the proliferating effect of splenic lymphocyte, the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclear cells (PBMCs), the cytotoxic effect on A549, SK-OV-3, SK-MEL-2, MCF-7 cells, the inhibitory effect on the activity of DNA topoisomerase I, the T/C% in ICR mice bearing S-180, the inhibitory effect of Cell adhesive of A549 Cells and SK-OY-3 Cells to complex extracellular matrix, the inhibitory effect on lung colonies, the change of lung tissue, the antiangiogenic activity, and the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line. Results and Conclusion : The results were obtained as follows : 1. In the cytotoxic effect on BALB/C mouse lung fibroblast Cell, GHT didn't show the significant cytotoxic effect on BALB/C mouse lung fibroblast cell compared to the control group. 2. In thymidine uptake assay, GHT showed the significant proliferating effect of splenic lymphocyte in proportion to the concentration. 3. In the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclea cells (PBMCs) of mice, GRT had no significant change to the normal group in CD4. However, GRT showed an increase to the normal group in CD8 and GHT in the only $1\mu\textrm{g}/ml$ category showed an increase to the normal group in B220. 4. In the cytotoxic effect of GRT on A549, SK-OY-3, SK-MEL-2 and MCF-7 cells, there was no significant cytotoxic effect compared to the control group. 5. In the inhibitory effect on the activity of DNA topoisomerase I, GHT in the $10\mu\textrm{g}/ml$ category showed the inhibitory effect on the activity of DNA topoisomerase I in proportion to the concentration. 6. In the T/C% in ICRmice bearing S-180, GHTtreated group showed 123.7% of T/C% compared to the control group. 7. In the inhibitory effect of cell adhesive of A549 Cells and SK-OV-3 Cells to complex extracellular matrix, GRT in the only $100\mu\textrm{g}/ml$ category showed the significant inhibitory effect compared to the control group. 8. In the inhibitory effect on lung colonies, GHT showed the significant inhibitory effect on lung colonies compared to the control group. 9. In the change of lung tissue, GHT showed a significant decrease of lung cancer growth, interalveolar fibrosis and hyaline material compared to the control group. In the development of lymphocyte around lung cancer cells and lung parenchymal, GHT showed the significant inducement efficacy compared to the control group. 10. In CAM assay, the antiangiogenic activity of GHT showed 30%. 11. In the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line, GHT had no significant inhibitory effect on MMP-2 and MMP-9 gene expression compared to the control group. According to the above results, it could be suggested that GHT has an antitumor activity and antimetastatic activity.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.1
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• pp.123-147
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• 2008

Objectives This study is to investigate how dose Ikhwang-San can be effective on SD rats which deteriorated immunity caused by methotrexate. Methods The test sample were dosed once a day for 14 days by gastric gavage at the beginning of dosage 1000, 500 and 250㎎/㎏/10㎖ from 2 days after last MTX-dosing, and the changes of the body and spleen weight, total number of blood leukocytes, total number of lymphocytes, the percentage of B-cell, T-cell, CD3+CD4+ T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the blood and spleen were observed. Results The changes of the body and spleen weight, the total number of blood leukocytes, the total number of lymphocyte in the blood and spleen were significantly increased in IHS Extracts groups comparing with the control group. The percentage of B-cell, T-cell, CD3+CD4+ T-cell in the blood and spleen were significantly increase in IHS groups and comparing with the control group. The ratio of CD4+/CD8+ T-cell in blood and spleen was significantly increased in IHS Extracts groups comparing with the control group. Conclusions According to those results, Ikhwang-San has good immunostimulating effect on SD rats which had deteriorated immunity caused by methotrexate.

• 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.

• Journal of Nutrition and Health
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• v.27 no.2
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• pp.153-161
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• 1994

We fed high trypotophan diet(3.5% tryptophan/diet(w/w) to mice for 7 days and treated then with 3 hour immobilization(IMMB) stress to investigate tryptophan metabolism and immunomodulation. The levels of serum tryptophan, brain tryptophan, serotonin(5HT) and 5-hydroxyindoleacetic acid(5HIAA) in the tryptophan diet fed animals were higher than those of the normal diet fed animals. Feeding tryptophan supplemented diet to stressed animal significantly decreased the levels of serum and brain tryptophan and 5HT levels. However, the amount of 5HIAA which is the metabolite of serotonin was increased in brain. Plasma corticosterone level was increased by the stress in both groups but the degree of this increase was smaller in high tryptophan fed animals. The relative numbers of CD8+ T cells, CD4+ T cells and B cells in spleen were decreased in high tryptophan diet fed and stressed animals compared to control diet fed and no stressed animals. CD8+ T cells decreased more than CD4+ T cells. The decrease of CD8+ T cells in high tryptophan fed and stressed animals was similar to that in high tryptophan fed animals or normal diet fed and stressed animals. Stress and tryptophan supplement acted synergistically to decrease the number of B cells. This study suggests that stress and tryptophan supplement could modify the number of lymphocyte cells, and indicates that the interaction of stress and tryptophan supplement on immune fuction depends on the types of immune cells.

• Journal of Korean Academy of Nursing
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• v.44 no.4
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• pp.446-457
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• 2014

Purpose: This study was done to evaluate the effects of psychosocial interventions on cortisol and immune response in adult patients with cancer. Methods: MEDLINE via PubMed, Cochrane Library CENTRAL, EMBASE, CINAHL and domestic electronic databases were searched. Twenty controlled trials (11 randomized and 9 non-randomized trials) met the inclusion criteria with a total of 862 participants. Methodological quality was assessed using the Cochrane's Risk of Bias for randomized studies and the Risk of Bias Assessment tool for non randomized studies. Data were analyzed using the RevMan 5.2.11 program of Cochrane library. Results: Overall, study quality was moderate to high. The weighted average effect size across studies was -0.32 (95% CI [-0.56, -0.07], p=.010, $I^2 $=45%) for cortisol concentration, -0.62 (95%CI [-0.96,-0.29], p<.001, $I^2 $=0%) for T lymphocyte (CD3) and -0.45 (95%CI [-0.74, -0.16], p=.003, $I^2 $=0%) for Th lymphocyte (CD4) numbers. Psychosocial interventions were not effective for Tc lymphocyte (CD4), NK cell, monocyte, and cytokine response. Conclusion: Although these results provide only small evidence of successful immune modulation, they support the conclusion that psychosocial interventions can assist cancer patients in reducing emotional distress and improving immune response.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.1
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• pp.20-25
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• 2009

Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of rejection in xenotransplantation is an acute cellular rejection by host $CD8^+$ cytotoxic T lymphocyte (CTL) cells that react to donor major histocompatibility complex (MHC) class I. The human cytomegalovirus (HCMV) glycoprotein Unique Short (US) 2 specifically targets MHC class I heavy chains to relocate them from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study we transfected the US2 gene into minipig fetal fibroblasts and established four US2 clonal cell lines. The integration of US2 into transgenic fetal cells was confirmed using PCR and Southern blot assay. The reduction of Swine Leukocyte Antigen (SLA)-I by US2 was also detected using Flow cytometry assay (FACS). The FACS analysis of the US2 clonal cell lines demonstrated a substantial reduction in SLA-I surface expression. The level (44% to 76%) of SLA-I expression in US2 clonal cell lines was decreased relative to the control. In cytotoxicity assay the rate of $CD8^+$ T cell-mediated cytotoxicity was significantly reduced to 23.8${\pm}$15.1% compared to the control (59.8${\pm}$8.4%, p<0.05). In conclusion, US2 can directly protect against $CD8^+$-mediated cell lysis. These results indicate that the expression of US2 in pig cells may provide a new approach to overcome the CTL-mediated immune rejection in xenotransplantation.

• Biomedical Science Letters
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• v.2 no.2
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• pp.167-174
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• 1996

Alcoholics increased susceptibility to microbial infection that is associated with decreased immunity. but there has been little experimental evidence to support alcoholics-induced increase of microbial infection directly in non-specific immunity. Therefore, we were used the method of phagocytic-plaque including all the stimulating factors for the phagocytosis, subtypes of lymphocytes and T-lymphocyte proliferation. The experimental groups were divided into 3 groups: (1) alcoholics who were hospitalized less than 1 week (newly hospitalized alcoholics), (2) alcoholics who were hospitalized more than 2 weeks (old hospitalized alcoholics), (3) healthy blood donors. We have studied 98 alcoholics and 35 healthy blood donors and control groups. A physician has checked the biological markers and diagnosed the body-condition alcoholics. The immunity and non-specific immunity on the alcoholics were analyzed by using the simultest kit and flow cytometry. Proliferation of the lymphocytes was analyzed by the phytohemmagglutinine mitogen. Phagocytosis and migration properties of leukocytes were identified on the layer formed by Staphylococcus aureus Cowan I strain. Biological markers of alcoholics and control groups, by such as blood glucose, ${\gamma}$-glutamyl transpeptidase and mean corpuscular volumes of red blood cells, were determined by biochemical and hematological methods. Compared with control groups, cluster of differentiation (CD)3+, CD8+ and CD19+ in alcoholic were more decreased except CD4+/CD8+ ratio. Proliferation of the T-lymphocytes, phagocytosis and migration properties of the leukocytes in alcoholics were decreased compared with those of control groups. According to the results observed in our experiment, they can be summerized as follows: 1, Cellular, humoral and non-specific immunities, are markedly decreased in alcoholics than those in control groups. 2. It is inferred that Phagocytic plaque formation is a very useful method to evaluate phagocytosis and migration properties of the alcoholic leukocytes 3. It is thought that the subtypes of lymphocytes, especially CD4+/CD8+ ratio, are essential methods to analyzed the alcoholic immunity. 4. Specific and non-specific immunity on the old hospitalized alcoholics was slightly increased, which depends upon the alcoholic medication.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.4
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• pp.597-606
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• 2008

Resorption of alveolar bone in periodontitis is due to excessive differentiation and activation of osteoclasts. Bacterial antigens causing periodontitis activates CD4 T cells, which leads to expressing RANK ligand (RANKL) on CD4 T cells. RANKL binds RANK on preosteoclasts or osteoclasts, and enhances the differentiation preosteoclasts into osteoclasts and the activation of mature osteoclasts. CD137, one of TNF receptor (TNFR) family, expressed on activated T cells binds with CD137 ligand (CD137L) on antigen presenting cells. Cross-linking of CD137 by CD137L acts as T cell co-stimulatory signals and, therefore, enhances the activation of T cell. In this study, I elucidated the biological responses of CD137L on (pre)osteoclasts and RANKL on T cells in the context of in vivo interaction between T cells and osteoclasts. RAW264.7, murine monocytic cells, constitutively express CD137L. Ligation of CD137L with anti-CD137L mAb inhibited RANKL-induced osteoclast formation in a dosedependent manner. Bone marrow cells are expressed CD137L by the treatment with M-CSF. Cross-linking of CD137L abolished M-CSF/ RANKL-evoked the formation of multi-nucleated osteoclasts. Both mouse CD4 and CD8 T cells are expressed RANKL following their activation. Ligation of RANKL with OPG, the decoy receptor for RANKL, inhibited both CD4 and CD8 T cell proliferation. These effects were attributed to RANKL-induced apoptosis. These data indicate that CD137L and RANKL on osteoclasts and T cells, respectively provide them with inhibitory signal.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.170-180
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• 1996

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the passibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen far each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantitfied and the influence of ${\beta}$-amyloid protein($A{\beta}$) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing $A{\beta}$ immunoreactivity was found in the T-sell dependent zone. FACS indicated that around 90% $CD_4(+)$ T-cells and 60% of $CD_8(+)$ T-sell were immunoreactive to $A{\beta}$ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the $A{\beta}$ immunoreactivity an cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted farm of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only law levels in the resting stale. Immunoblot was carried out an the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that $A{\beta}$ band of immature farm under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal $A{\beta}$ specific(4G8) and polyclonal APP antibodies did not inhibit the [$^3H$]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific $A{\beta}$ and polyclonal APP antibody. These results suggest that APP is expressed in T-cell and might be closely associated with the function of T-cells.

• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.