• IMMUNE NETWORK
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• v.23 no.1
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• pp.10.1-10.16
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• 2023

Memory T (Tm) cells protect against Ags that they have previously contacted with a fast and robust response. Therefore, developing long-lived Tm cells is a prime goal for many vaccines and therapies to treat human diseases. The remarkable characteristics of Tm cells have led scientists and clinicians to devise methods to make Tm cells more useful. Recently, Tm cells have been highlighted for their role in coronavirus disease 2019 vaccines during the ongoing global pandemic. The importance of Tm cells in cancer has been emerging. However, the precise characteristics and functions of Tm cells in these diseases are not completely understood. In this review, we summarize the known characteristics of Tm cells and their implications in the development of vaccines and immunotherapies for human diseases. In addition, we propose to exploit the beneficial characteristics of Tm cells to develop strategies for effective vaccines and overcome the obstacles of immunotherapy.

• Korean Journal of Medicinal Crop Science
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• v.13 no.5
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• pp.213-218
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• 2005

Phellinus linteus (PL), one of the immune-regulatory substances, is recognized to play the role in the metabolic process on inflammation and immunity. It has been traditionally used in the oriental medicine to treat inflammatory related disease. The purpose of this study was to evaluate the effects of water extracts of PL on the mesenteric lymph node lymphocytes immune function in the ICR male mice. Control mice received vehicle only. The PL treated mice were administered the respective extract by oral gavages for 4 weeks. IgE concentrations in serum and MLN lymphocytes were significantly lower in PL treated mice than in control mice. PL increased the proportion of $CD4^+\;and\;CD8^+$ T cells in MLN lymphocytes. PL significantly decreased Th2 cytokine concentrations and mRNA expression levels in cytokine secretions. Therefore, water extracts of PL modulate inflammatory parameters through regulation of immunoglobulin production resulting from decreased Th2 cytokine secretion and mRNA expression levels and reduce pro-inflammatory cytokine secretion and mRNA expression in MLN lymphocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.265-271
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• 2014

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

• Journal of Nutrition and Health
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• v.32 no.7
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• pp.781-786
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• 1999

This study was designed to investigate the effects of vitamin E supplementation on radical scavenger activity and immune responses in female judo athletes(n=18). The age and sex matched sedentary students were used as controls(n=15). The initial plasma vitamin E concentration, lipid peroxide level and radical scavenger activity (RSA) were not different between two groups. The supplementation of $\alpha$-tocopheryl acetate(400IU/d) for 4 weeks significantly increased plasma vitamin E concentration of the subjects in both groups. In addition, the decrease in thiobarbituric acid reactive substance(TBARS)(p<0.05) and enhancement of RSA(p<0.05) were observed in both groups. Percentages of total T-cells in the athletic group was lower than that in the control group(p<0.05). However, the ratio of CD4 / CD8(helper T-cal $l^pressor T-cell) was higher in the sports group, due to more decrease in CD8 subset than in CD4 subset. The concentrations of IgG and IgM in the sports group were significantly lower than those in the control group(p<0.05). Therefore, severe training of the athletic group seems to be associated with the changes of supplementation. In conclusion, vitamin E supplementation (400IU/d, 4 weeks) of the female university students improved antioxidative activities of the blood, by decreasing lipid peroxide and enhancing radical scavenger activity. Percentages of T lymphocytes and IgG and IgM concentrations in the athletic group were lower than those in the control group. Meanwhile, vitamin E supplementation had no effects on immune status in both groups.ps.

• The Journal of Dong Guk Oriental Medicine
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• v.5
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• pp.187-196
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• 1996

Alcohol is a major risk factor for several diseases and especially excessive, long-term alcohol consumption are caues the damage of immunity such as the inhibiton of secretion of lymphokine and proliferation of immune component cell. This study observed that the inhibition of T lymphocytic differentiation and secretion of interleukin 2(IL-2) induced in thymus of ICR mouse by chronic alcohol administration. After 8% alcohol voluntary administered for 120 days, the thymic tissue immunohistochemically stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly-2(CD8), and IL-2 receptor(CD25R) after embedding with paraffin. The results were as follows. 1. The size of thymic medulla in test group reduced than control group. 2. The number of helper T lymphocyte, cytotoxic T lymphocyte, and IL-2 receptor were decreased in thymic medulla and cortico-medullary junction of test group and the degree of CD4, CD8, and CD25R positive reaction were soften in test group. These results indicated that the secretion of IL-2 in thymus was inhibited by chronic alcohol administration and subsequently prevent to differentiate from thymocytes to T lymphocytes. As this view, cell mediated immunity were reduced by chronic alcohol administration.

• Natural Product Sciences
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• v.13 no.2
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• pp.123-127
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• 2007

We investigated effect of small black soybean fraction (SBSF) T cell-mediated responses for tumor surveillance and proliferation in leukemia cells in vitro. Each SBSF butanol fraction (SBSFBu) and SBSF chloroform fraction (SBSFCh) was administered p.o. once a day far 21 days in BALB/c mice and then levels of serum cytokines and subpopulation of lymphocytes were measured. Moreover, SBSF fraction was treated into the cultured various cell lines for proliferation in leukemia cell lines, NO production by RAW264.7 cells, and expression of p53 gene in U937 leukemia cells. These results showed that SBSFBu increased levels of serum IL-4but not IL-2 and IFN-${\gamma}$, and increased expression of CD4$^+$ T cells and CD8$^+$ T cells in splenocytes in vivo, while SBSFCh increased levels of serum IL-2 and IFN-${\gamma}$ but decreased IL-4, and increased CD8$^+$ T cells but not CD4$^+$ T cells. Moreover, both of SBSFBu and SBSFCh inhibited proliferation of HL60, U937, and L1210 leukemia cell lines in a dose-dependent manner, up-regulated NO production by RAW264.7 cells in a dose-dependent manner, and enhanced expression of p53 gene in U937 leukemia cells. Our findings indicate that SBSFBu and SBSFCh may enhance T cell-dependent immune responses, and that both of SBSFBu and SBSFCh may inhibit proliferation of leukemia cells by up-regulation of NO production and expression of p53 gene.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2419-2423
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• 2015

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

• Journal of Food Hygiene and Safety
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• v.24 no.1
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• pp.78-85
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• 2009

This study was performed to investigate the effect of extract mixture(IPGE) drink from Inonotus Obliquus, Phellinus Linteus and Ganoderma Lucidum on hematopoietic stem cells and lymphocyte subset[lymphocyte, $CD4^+T$ cell, $CD8^+T$ cell, Natural Killer(NK) cells] of blood in 37 participants who were healthy and about $40{\sim}70$ years old. They were divided into two groups; extract mixture drink administration group(n=27) and placebo administration group(n=12). They were given the test drink daily for 4 weeks. Blood was obtained from the subjects every two week in the beginning of administration day to evaluate the $CD34^+$ hematopoietic stem cells and immune cells. As results, $CD34^+$ hematopoietic stem cells were significantly increased after taking IPGE drink for 4 weeks compared to that before taking the drink (p<0.001). There was no significant changes in number of lymphocytes, $CD4^+T$ cells, $CD8^+T$ cells, NK cells and in the ratio of $CD4^+/CD8^+$ cell after taking the test drink. From these results, it was suggested that IPGE have a good health effect by promoting the proliferation of the hematopoietic stem cells.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.31-37
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• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.1
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• pp.26-36
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• 2024

Purpose: We investigated the role of CD8⁺T cells as host immune factors in pediatric patients with Helicobacter pylori gastritis. Methods: Gastric mucosal tissue and blood samples were collected from 39 children, including 11 children with H. pylori infection and 28 children as controls. Anti-CD8 and anti-T-bet antibodies were used for immunohistochemistry of the gastric mucosa. For the cell surface and intracellular staining, peripheral blood mononuclear cells were stained with anti-IL7Rα, anti-CX3CR1, anti-CD8, anti-T-bet, and anti-IFN-γ antibodies. Cytokines of sera such as tumor necrosis factor alpha (TNF-α) and CX3CL1 were analyzed using enzyme- linked immunosorbent assay (ELISA). Results: In the immunohistochemistry of gastric mucosa, the frequency of CD8⁺ and T-bet⁺ T cells cells was higher in the H. pylori-positive group than in the control group (26.9± 7.8% vs. 16.9±3.3%, p<0.001; 5.0±2.5% vs. 2.2±0.7%, p=0.001). Between the control and H. pylori-positive groups, the frequency of IL-7Rα^lowCX3CR1⁺ CD8⁺ and T-bet⁺ INF-γ⁺ CD8⁺ T cells were not significantly different between surface and intracellular staining, respectively (40.4±24.0% vs. 38.2±17.8%, p=0.914; 40.4±24.0% vs. 38.2±17.8%, p=0.914). In the ELISA, no significant differences in TNF-α and CX3CL1 concentrations were observed between the control and H. pylori-positive groups (34.3±12.1 pg/mL vs. 47.0±22.6 pg/mL, p=0.114/0.5± 0.1 pg/mL vs. 0.5±0.1 pg/mL, p=0.188). Conclusion: CD8⁺ T and Th1 cells, which secrete IFN-γ, might play important roles in the mucosal immunity of the stomach in children with H. pylori infection.