• Toxicological Research
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• v.29 no.2
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• pp.115-120
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• 2013

To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, and the proportion of B cells and $TNF{\alpha}$ level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was $3.4{\mu}g/m^3$, $112.3{\mu}g/m^3$, and $2.3{\mu}g/m^3$ in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (< $0.1{\mu}g/m^3$). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p<0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.334-342
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• 1992

Background: The activated T lymphocyte by inhalaed mycobacterial antigen may evoke cell-mediated immunity in patients with active pulmonary tuberculosis. These activated lymphocyte may influence the response of tuberculin-purified protein derivative (PPD) in skin test. But occasionally, anergy to PPD appear in patients with pulmonary tuberculosis in spite of active stage. Thus we evaluated the effect of change of subtypes of lymphocyte in bronchoalveolar lavage fluid (BAL) and peripheral blood on anergy to PPD in patients with active pulmonary tuberculosis. Method: We performed tuberculin skin test and flow-cytometry analysis of lymphocytes obtained from BAL fluid and peripheral blood in 11 healthy normal volunteers and 20 patients with active pulmonary tuberculosis. Results: 1) The composition of lymphocyte significantly increased in patients with active pulmonary tuberculosis when compared with that in healthy control ($25.2{\pm}4.8$ vs $6.5{\pm}1.3%$, p<0.01), but composition of monocyte significantly decreased ($69.6{\pm}5.7$ vs $89.2{\pm}1.4%$, p<0.05) in analysis of BAL fluid. 2) There were no differences in compositions of cells in BAL fluid between responders and no-responders to PPD. 3) The compositions of CD3 (+), CD4 (+), CD3 (+) IL-2R (+), CD3 (+) HLA-DR (+) significantly increased in BAL fluid when compared with those in peripheral blood in patients with active pulmonary tuberculosis. But the composition of CDS (+), CD4/CDS were not different between BAL fluid and peripheral blood. 4) There were no correlations between response to PPD and compositions of cells and lymphocyte subtypes in BAL fluid and peripheral blood in all patients with tuberculosis, responders, and no-responders, respectively. Conclusion: From these results, we suggest no direct relationship between compositions of inflammatory cells in bronchoalveolar lavage fluid and we could not rule out the possibility of compartmentalization of activated lymphocyte involving in anergy to PPD in skin test in patients with active pulmonary tuberculosis.

• The Journal of Dong Guk Oriental Medicine
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• v.5
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• pp.197-207
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• 1996

As a mood-altering drug, long-term alcohol consumption have significant harmful effects on the human body and people's mental functioning. This study observed that the suppression of cell mediated immunity induced in spleen of ICR mouse by long-term alcohol administration. After 8% alcohol voluntary administered for 120 days, the splenic tissue irnmunohistochemically stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly-2(CD8), IL-2 receptor(CD25R) and NK-1.1(CD56) after embedding with paraffin. The results were as follows. 1. The size of marginal zone in splenic white pulp was diminished and the number of macrophage in marginal zone was decreased in test group than control group. 2. After alcohol administration, the number of Helper T lymphocyte, cytotoxic T lymphocyte, and IL-2 receptor were decreased in periarterial lymphatic sheaths of white pulp and penicilla artery of red pulp and the degree of CD4, CD8, and CD25R positive reaction were soften. 3. In test group, the number of NK cell were decreased. These results indicated that the secretion of lymphokine as IL-2 was inhibited by long-term alcohol administration and subsequently prevent to activate and proliferate splenic T lymphocytes and NK cells as cell mediated immunity component.

• Korean Journal of Microbiology
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• v.49 no.3
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• pp.221-227
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• 2013

Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping B cells to produce specific antibodies against viral proteins. The antiviral activity of T cells is usually affected by immune-regulatory factors that express on surface of T cells. Recently, many researchers have investigated the relationship between effector functions of virus specific T cells and characteristics of immune regulatory factors (e.g., CD28, CD25, CD45RO, FoxP3, PD-1, CTLA-4). In particular, Immune inhibitory molecules such as forkhead box P3 (FoxP3), programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with T-cell dysfunction. They are shown to be up-regulated in chronic viral diseases such as hepatitis B, hepatitis C or human immunodeficiency virus infection. Therefore, the positive correlation between viral persistence and expression of immune regulatory factors (FoxP3, PD-1, and CTLA-4) has been suggested. In this review, the roles of immune regulatory factors FoxP3, PD-1, and CTLA-4 were discussed in chronic viral diseases such as HIV, HBV, or HCV.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.83-88
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• 2015

CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) have been shown to play a regulatory or suppressive role in the immune response and are possibly relevant to the pathogenesis of autoimmune diseases. In the present study, we attempted to investigate the frequency of CD4+CD25+ Tregs in peripheral blood (PB) of collagen-induced arthritis (CIA) rats during the development of arthritis, to determine whether their frequency is involved in the immunoregulation of this disease. The results showed that normal rats had similar frequencies of CD4+CD25+ Tregs in PB during the experiment time, expressed as a percentage of CD4+CD25+Foxp3+ T cells among the CD4+ T lymphocyte population. In contrast, the frequency of CD4+CD25+Foxp3+ T cells in CIA rats was found to change during the development of arthritis. In CIA rats, there is a significant negative correlation between the frequency of CD4+CD25+Foxp3+ T cells and paw swelling (r=-0.786, p< 0.01). The relationship between the frequency of CD4+CD25+Foxp3+ T and immune activation was not found in normal rats. During the time course, the frequency of CD4+CD25+Foxp3+ T was lower in CIA rats than in normal ones. The data suggest that the frequency of PB CD4+CD25+ Tregs may be a promising marker for arthritis activity.

• 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.

• Biomedical Science Letters
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• v.20 no.3
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• pp.147-155
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• 2014

It has well studied that immune cells are strongly related to tumor progression and tumor suppression. To identify the difference of immune cell between tumor bearing mice and normal mice, we examined systemically the immune cell of CT26 tumor bearing mice on 21 days after tumor cell administration. As previously reported, CD4+ and CD8+ T cells population of tumor bearing mice significantly decreased 38% and 30% on day 21 compared to that of normal mice, respectively. All subpopulation of CD4 and CD8+ T cell significantly decreased, except CD49b+ T cell subpopulation. But, myeloid cell population ($CD11b^{high}$ and all Gr-1+ subpopulation) of tumor bearing mice significantly increased on day 21. Especially, all subpopulation of CD11b+Gr-1+ cell of tumor bearing mice significantly increased on day 21. Also, Foxp3+$CD25^{high}$ CD4 T cell (regulatory T cells) population significantly increased on day 21. These results suggest that tumor can induce the decline of T lymphocyte and the expansion of myeloid cells and regulatory T cells, and provide the basic information for the study of tumor immunology.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1576-1583
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• 2006

In order to investigate the effect of Goamshimshinhwan(GASSW) on SD rats with deteriorated immunity caused by methotrexate. Methotrexate was fed to the SD rats once a day for 4 days. After the immune responses of the at a dosage 1,000, 500 and 250mg/kg/10ml. and the changes on body weight and gains, spleen weight, total blood leukocyte numbers, total lymphocyte numbers, the percentage of B-cell, T-cell, CD3+CD+4 T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the bolld and spleen were observed. In addition, the serum IL-2 levels and productivity of IL-2 of splenic cells were also demonstrated in this study. The changes on body weight were increased significantly in 100 and 500mg/kg of GASSW groups and the changes on body gain were increased significantly in 1000mg/kg of GASSW groups as compared with control group. The changes on the spleen weight (absolutely or relatively) were increased significantly in all GASSW groups as compared with control group. The total blood leukocyte numbers were increased significantly in 1000 and 500mg/kg of GASSW groups as compared with control group. The total lymphocyte numbers were increased significantly in all GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW goups in spleen as compared with control group. The percentage of B-cell and T-cell were increased significantly in 1000mg/kg of GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW groups in spleen as compared with control group. The percentage of CD3+CD4+ T-cell and the serum IL-2 levels and productivity of IL-2 of splenic cells were increased significantly in 100 and 500 mg/kg of GASSW groups in the blood and spleen as compared with control group. The percentage of CD3+CD8+ T-cell were increased significantly in 1000mg/kg of GASSW groups only in spleen as compared with control groups. The CD4+/CD8+ T-cell ratios were increased significantly in 1000 and 500mg/kg of GASSW groups only in the blood as compared with control group. Goamshimshinhwan(GASSW) has immuno-stimulating effect on SD rats with deteriorated immunity caused by methotrexate.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

• Journal of Korean Medicine Rehabilitation
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• v.15 no.1
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• pp.127-141
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• 2005

Objectives : This study was performed to investigate the effects of Gamichangbaek-san(Jiaweichangbai-san) on anti-inflammatory, analgesic, anti-febrile and immune response on the arthritis of carrageenan-induced animals. Methods and Materials : Rats were classified into control and sample groups which are 7 individuals each for the experiments about anti-inflammatory and anti-febrile. Each of the 7 mice were classified into normal, control, sample groups for the analgesic experiments. Gamichangbai-san(Jiaweichangbai-san) was administered to sample group and normal saline was administered to normal and control groups. Arthritis was induced by injection of 1% carrageenan $0.1m{\ell}$ and Gamichangbaek-san(Jiaweichangbai-san) was administered after 30 minutes. The change of edema in Carrageenan-induced Arthritic Rats' Paws was measured after 1 hour and 5 hours from the injection of carraqeenan with Plethysmometer(7150, UGO BASILE, ltaly) by Winter' method. WBC, Lymphocyte and ESR were measured by heart puncture and CD4+ T cell, CD8+ T cell and CD4+/CD8+ T cell ratio were measured from the spleen tissue. Writhing syndrom was measured with Tail flick unit(UGO BASILE, Italy) in the experiments conducted to check the analgesic activity. The temperature of the paws of carrageenan-induced arthritic rats was measured by Laser thermometer. Rectal temperature was measured by Yeast's method in anti-febrile experiments. Immune response was measured by CD4+, CD8+ T cell ratio and CD4+/CD8+ T cell ratio. Results : 1. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased the increase rate of Paw Edema effectively with statistical significance. 2. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased WBC, Lymphocyte and ESR with statistically high significance. 3. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) did not show significant analgesic effect, but the Pressure pain threshold of the paws was increased with statistical significance. 4. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased rectal temperature effectively and had an anti-febrile effect about the febrile of a joint with statistical significance. 5. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) increased CD4+ T cell ratio with statistically high significance and increased CD+8 T cell ratio with statistical non significance but increased CD4+/CD8+ T cell ratio effectively with statistical significance, too. Conclusions : According to the above results, it can be concluded Gamichangbaek-san(Jiaweichangbai-san) showed the treatment effects on the artificial arthritis resulted from carageenan in rats and it is suggested that more interest and study in the security for the clinical use were needed.