• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.232-239
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• 2010

Stems and roots of Acanthopanax koreanum Nakai were extracted with water and treated on immune cells in order to determine their immunomodulatory activites. Various Th-1 type cytokines were measured using ELISA including interleukin (IL)-2, IL-12, interferon-gamma (IFN-$gamma$), and tumor necrosis factor-alpha (TNF-$\alpha$) secreted by dendritic cells, T-cells, intestinal epithelial cells, natural killer cells, and macrophages. As a result, there was a significant increase in IL-12 and IFN-$\gamma$, secretion, but there was no change in the secretion of TNF-$alpha$. Additionally T-cells slightly increased the secretion of IL-2, but there was a significant increase of IL-2 in intestinal epithelial cells. Therefore, our results suggest that A. koreanum Nakai may act as an immunomodulator by stimulating the cell-mediated immunity which can help the immune system defend against infections or cancer cells.

• Molecules and Cells
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• v.39 no.6
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• pp.468-476
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• 2016

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether $PLZF^+$ innate T cells also affect the development and function of $Foxp3^+$ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant $PLZF^+$ CD4 T cells and invariant natural killer T cells, respectively, revealed that $Foxp3^+$ T cells in these mice exhibited a $CD103^+$ activated/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ mice, indicating that the acquisition of an activated/ memory-like phenotype was dependent on $PLZF^+$ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-${\beta}$ enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/ memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of $CIITA^{Tg}PIV^{-/-}$ mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that $PLZF^+$ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

• Journal of Life Science
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• v.33 no.3
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• pp.295-303
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• 2023

Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.406-411
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• 2011

Background: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant $V{\alpha}{\beta}$ TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. Methods: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells by using Gene Set Enrichment Analysis (GSEA) method. Results: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells. Conclusion: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.

• Journal of Life Science
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• v.23 no.12
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• pp.1532-1540
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• 2013

T-box transcription factor 2 (Tbr2) is a member of the T-box family of transcription factors and it plays an important role in brain development, progenitor cell proliferation, and the modulation of differentiation and function in immune cells, such as CD8+ T cells and natural killer cells. This study aims to elucidate the involvement of Tbr2 in the pathophysiological events following pilocarpine-induced status epilepticus in mice. Status epilepticus resulted in prominent neuronal cell death in discrete brain regions, such as CA3, the hilus, and the piriform cortex. Interestingly, when the immunoreactivity of Tbr2 was examined two days after status epilepticus, it was transiently increased in CA3 and in the piriform cortex. Tbr2-positive cells in CA3 and the piriform cortex were double-labeled with CD11b, a marker of microglia and a subset of white blood cells, such as monocytes, CD8+ T cells, and natural killer cells. Moreover, the double-labeled cells with Tbr2 and CD11b showed amoeboid morphology, and this data indicates that Tbr2-expressing cells may be reactive microglia or infiltrating white blood cells. Furthermore, clustered Tbr2-positive cells were observed in the platelet endothelial cell adhesion molecule-1 (PECAM-1)-positive blood vessels near the CA3 area, which suggests that Tbr2-positive cells may be infiltrating the white blood cells. Based on this data, this study is the first to indicate the involvement of Tbr2 in neuropathophysiology in status epilepticus.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.26 no.3
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• pp.286-292
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• 2016

Objectives: This study aimed to evaluate the effects of chronical exposure to high-level dusts on cellular immune function. Methods: The subjects were 110 male workers, among whom 60 were chronically exposed to high-level dusts in mica, limestone and iron mines. The remaining 50 were office workers. Ambient total, respirable dust and crystalline silica in the workplace were sampled using personal air samplers and analyzed according to NIOSH method 0500. Serum levels of hydrogen peroxide, lipid peroxide and superoxide misutase activity were measured using absorption chromatography. The subpopulations of CD4+, CD8+, natural killer cells (CD16+) and CD3+ T-lymphocytes were examined by two-color staining using monoclonal antibodies. Results: The concentration of hydrogen peroxide was significantly higher in exposed workers and superoxide dismutase activity was significantly higher in control workers. No significant difference in numbers of T-lymphocyte subpopulations were observed between exposed and control workers. A significant correlation in exposed workers was observed among total dusts, respirable dusts and crystalline silica. Hydrogen peroxide was significantly correlated with total dust (r=0.720, p<0.01), respirable dust (r=0.770, p<0.01) and crystalline silica (r=0.678, p<0.01). Concentration of hydrogen peroxide showed a significantly negative correlation with numbers of CD8+ cells (r=-0.274, p<0.01), CD3+ cells (r=-0.222, p<0.01) and natural killer cells (r=-0.556, p<0.01). Conclusions: These results suggest that chronical exposure to high-level dust affects cellular immune function and effects might mediate through reactive oxygen species and inflammatory response.

• Journal of Life Science
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• v.8 no.3
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• pp.257-262
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• 1998

Benzo(a)pyrene(B(a)P), an extensively studied polycyclic aromatic hydrocarbon(PAH), is a common contaminant produced through the burning of fossil fuels, particularly coal, and from the exhaust products of internal combustion engines. It produces a wide range of toxicities, including carcinogenicity in experimental animals. B(a)P has been shown to suppress systemic immunity in experimental animals, which may contribute to the growth of the chemical-induced tumors. Using colorimetric MTT assay natural killer(NK) cell-mediated growth inhibition of tomor cell was measured in normal and B(a)P-exposed C57BL/6 mice. Non-adherent splenocytes of normal or B(a)P-exposed mice were cultured with Yac-1 cells at four different effector/target(E/T) cell ratios ranging from 200/1, 100/1, 50/1, and 25/1 in an assay volume of 0.1 ml. After the optical density of culture wells containing MTT solution was measured at a wavelength of 540 nm, the percentage of dead cells relative to the control target cell number was calculated. The NK activity of B(a)P-exposed mice was markedly lower than that of non-exposed mice group at all E/T ratios. These results indicated that suppression of NK cell activity may play a role in allowing for the growth of tumors.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.307-313
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• 2015

The present study investigated the immunomodulatory effects of Curcuma longa L. ethanol extracts on natural killer (NK) cells and T cells. We treated Curcuma longa L. ethanol extracts at concentrations of 20, 50, 100, and $150{\mu}g/mL$ to murine NK cells co-incubated with YAC-1 cells. Curcuma longa L. ethanol extracts resulted in increased NK cell activity compared to the control group at all concentrations. In the groups treated with Curcuma longa L. ethanol extracts, CD69 and IFN-${\gamma}$ expression levels significantly increased compared to the control group at 100 and $150{\mu}g/mL$. In addition, Curcuma longa L. ethanol extracts induced significant elevation of CD8+ T cell numbers in a dose-dependent manner. However, Curcuma longa L. ethanol extracts also led to reduction of CD4+ T cell and MHCII numbers. The findings of this study suggest that Curcuma longa L. ethanol extracts could enhance the immune response through activation of NK and cytotoxic T cells due to a proliferative shift of antigen presentation from MHCII to MHCI, presumably.