• IMMUNE NETWORK
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• v.21 no.6
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• pp.44.1-44.15
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• 2021

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2K^b molecules, and then the natural peptide epitopes associated with the H-2K^b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA_257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2K^b complex-specific CD8⁺ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8⁺ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

• Preventive Nutrition and Food Science
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• v.8 no.1
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• pp.96-104
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• 2003

Ginger (Zingiber officinale Roscoe) is traditionally used as appetite enhancer, improver of the digestive system, antithusive, anti-cold, antipyretic, analgesic, and antiinflammation. In vitro evaluation using human lymphocyte cultures showed almost similar indication with those in in vivo mouse study, NK cell lysing activity was improved significantly. Proliferation activity of B and T cells, and CD3$^{＋}$ and CD3$^{＋}$CD4$^{＋}$T cell subset were better observed using oleoresin or gingerol and shogaol fractions. Although there were higher activities in gingerol, the improvement was almost equal to that by oleoresin. Shogaol did not show better improvement except at higher concentration. It could be concluded that treatment with single bioactive compound, such as gingerol, did not show significant effects compared to oleoresin, the crude extract. In human study, involving healthy male adult, the improvement of NK cell lysing activity was again demonstrated and even more apparent. The mechanism involved in the protection seemed to be through the antioxidant activity of gingerol. However, other mechanism underlying the improvement of NK cell lysing activity must be involved since this improvement seemed to be specifically toward NK cell activity. Since NK cells ave specific for the elimination of virus-infected cell and mutated cells, this positive effect on the immune system are very interesting. This work has also scientifically proved that the traditional beliefs that ginger had preventive effects on common cold appeared to be reasonable.

• Journal of Ginseng Research
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• v.22 no.4
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• pp.324-330
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• 1998

We Previously reported that Polysaccharide Isolated from panax ginseng C. A. Meyer, stimulates murine splenocytes to proliferate and to be cytotoxic against a wide range of tumor cells in MHC non-restricted manner:) Therefore, we examined the cytokine mRNA expression induced by the ginseng polysaccharide in this paper. This study demonstrates that the ginseng polysaccharide stimulates Thl type cytosine expression such as IL-2 and IFNY, and macrophage type cytokine expression such as IL-lc and GM-CSF in a dose-dependent manner at different time: IL-2 mRNA was induced at 30 min, IL-la, GM-CSF mRNA at 3 hr, IFNY at 6 hr after the ginseng polysaccharide treatment. In contrast with these, Th2 type cytokine expression such as IL-4 and IL-5 was not induced. The generation of the ginseng polysaccharide-activated killer cells which was induced at the optimal doses of 50 pEyml was neutralized in the presence of anti-lL-2, anti-lFNy, anti-IL-l ${\alpha}$ antibodies, showing the importance of these cytokines produced by the ginseng polysaccharide. In flow cytometry analysis, the blastogenesis of IgM+ cells was induced on day 3 and the number of Thy 1.21 cells, CD4+ and CD8+ cells was increased on day 5. The ginseng polysaccharide also induced blastogenesis of T cells. In conclusion, the ginseng polysaccharide may have considerable antitumor immunotherapeutic modality by stimulating the cytokine production from Thl cells and macrophage and by proliferating lymphocytes.

• Journal of Society of Preventive Korean Medicine
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• v.4 no.2
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• pp.57-71
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• 2000

BACGROUND: To examine effect of omahwan(烏麻丸)-赤何首烏(Polygonum multiflorum THUNB.), 白何首烏(Cynanchum wilfordii H.), 黑芝流(Sesamum indicum L.)-on the aged human immune system a series of humoral immunological parameters was compared in aged female (age 60-70 years) before and after administration of omahwan(烏麻丸). METHODS: Peripheral blood was obtained from fifteen healthy young (age 20-29, mean=66.3) female volunteers. B cell, T cell(T cells, T helper, and T suppressor/ cytotoxic) subsets was examined with specific monoclonal antibodies and isotype controls, using dural color flow cytometer IL-2 was examined with ELISA kit RESULT: By comparing the immune characteristics of the younger and elder groups the total ratio of T-cell, CD8 T-cell and quantify of IL-2 was significantly lower while CD4/CDB ratio was considerably greater in the elder group. ( p(0.05, student t-test) After giving Omahwan for 30 days to the elder group, by comparing the ratio before and after Prescription the total T cell and CD8 T cell ratio was considerably greater after prescription (p(0.05, Paired t-test) The quantity of IL-2 tended to increase after prescription but has no statistical meaning. CONCLUSION: The results indicate that administration of Omahwan(烏麻丸) differentially affects various aspects of the immune system in aged human.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8947-8950
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• 2014

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-${\alpha}$. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-${\alpha}$. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.40-51
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• 2006

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and occurrence of grossly deleted nef genes ($g{\Delta}nef$), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined whose the annual decrease in CD4 T cells was less than $20/{\mu}l$ over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and products were sequenced directly. Patient CD4 T cell counts decreased from $444{\pm}207/{\mu}l$ to $294{\pm}177/{\mu}l$ over $136{\pm}23$ months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of $13.3/{\mu}l$. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 92 out of the 479 genes revealed $g{\Delta}nef$. The deletion extended outside the nef gene in 25 $g{\Delta}nef$ obtained from 6 patients. The proportion of samples with $g{\Delta}nef$ (34.3%) was significantly higher than 4.8% in control patients (P<0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P<0.01). These data suggest the possibility that occurrence of $g{\Delta}nef$ might be associated with long-term intake of KRG.

• Journal of Acupuncture Research
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• v.23 no.6
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• pp.61-76
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• 2006

To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of herbal-accupunture with Orostachys japhonicus A.Berger, infusion solution put into Kansu(BL18) of mouse induced by Colon26-L5 human colon cancer cells, which are corresponding to humanbody. We observed the change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen and kidney, histological analysis on tissue metastasis of liver, splenic cell proliferation, the expression of cytokine gene, the number of CD4+, CD8+, CD9+ and NK cell, and concluded like this. The results were obtained as follows ; 1. In acute and sub-acute cytotoxicity experiment, significantly signs were not appeared in all groups. 2. Antimetastatic experiment in vitro and in vivo showed that Orostachys Japhonicus A.Berger Herbal-acupuncture at Kansu(BL18) has antimetastatic effects. 3. The spleen cells proliferation of the experimental groups treated with Orostachys Japhonicus A.Berger infusion solution extract has increased significantly compared with that of the control group. 4. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. 5. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Above the results revealed that herbal-accupunture with Orostachys Japhonicus A.Berger infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

• Parasites, Hosts and Diseases
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• v.50 no.4
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• pp.301-308
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• 2012

In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of $CD19^+$ B cells was observed as early as week 1 post-infection while $CD4^+/CD8^+$ T cells were down-regulated. Accumulation of $Mac1^+$ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-${\alpha}$ mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-$1{\beta}$ expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-${\beta}$ were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-${\beta}$ and IL-4 during the early stages of infection.

• Molecules and Cells
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• v.43 no.5
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• pp.479-490
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• 2020

Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4⁺ T cells, CD8⁺ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

• Journal of Animal Science and Technology
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• v.50 no.6
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• pp.849-856
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• 2008

The present study was undertaken to investigate specific immune response of Rubus coreanus Miquel (raspberry) in pig spleen lymphocytes and gene expression induced by the extracts of raspberry using gene chip technology. The 70% ethyl alcohol extracts of raspberry were treated to pig spleen lymphocytes. The extracts of raspberry stimulated the proliferation of splenocytes and increased the population of CD3 & CD4 T-cells and B-cells in pig spleen lymphocytes. The extracts of raspberry improved immune response by increasing the viability of splenocytes. In microarray study we found eight genes were significantly up- regulated by the extracts of raspberry in pig splenocytes, including genes known to be involved in cell structure and immune response, particularly microtubule-associated protein 4, cytoplasmic dynein heavy chain, tumor necrosis factor alpha, lymphotoxin-beta receptor precursor. However, ten genes were down- regulated by the extracts of raspberry treatment.