• Asian-Australasian Journal of Animal Sciences
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• 제26권4호
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• pp.463-469
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• 2013

Cluster of differentiation 4 (CD4) is mainly expressed on $CD4^+$ T cells, which plays an important role in immune response. The aim of this study was to detect the association between polymorphisms of the CD4 gene and T lymphocyte subpopulations in pigs, and to investigate the effects of genetic variation on the CD4 gene expression level in immune tissues. Five missense mutations in the CD4 gene were identified using DNA pooling sequencing assays, and two main haplotypes (CCTCC and AGCTG) in strong linkage disequilibrium (with frequencies of 50.26% and 46.34%, respectively) were detected in the population of Large White pigs. Our results indicated that the five SNPs and the two haplotypes were significantly associated with the proportions of $CD4^-CD8^-$, $CD4^+CD8^+$, $CD4^+CD8^-$, $CD4^+$ and $CD4^+/CD8^+$ in peripheral blood (p<0.05). Gene expression analysis showed the mRNA level of the CD4 gene in thymus was significantly higher than that in lymph node and spleen (p<0.05). However, no significant difference was observed between animals with CCTCC/CCTCC genotype and animals with AGCTG/AGCTG genotype in the three immune tissues (p>0.05). These results indicate that the CD4 gene may influence T lymphocyte subpopulations and can be considered as a candidate gene affecting immunity in pigs.

• 미생물학회지
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• 제47권4호
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• pp.342-347
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• 2011

인체의 바이러스 감염 방어기전에서 T 림프구는 중요한 역할을 한다. 하지만, 만성 C형 간염 바이러스의 일차적 복제장소인 간염 환자의 간에서 분리된 HCV 특이 T 림프구는 심각한 기능결핍을 보인다. 이러한 T 림프구 기능결핍의 이유로는 PD-1, CTLA-4 등 면역억제 물질의 발현, 또는 간에서 특이적으로 유도되는 면역내성(immune tolerance)이 있으나, 간세포(hepatocytes)와 HCV 특이 T 림프구의 상호작용에 대해서는 명확하게 확립되어 있지 않다. 따라서 본 연구에서는 HLA(human leukocyte antigen) A2+ 간암세포주(human hepatoma cell line; huh7.5)가 항원제시(antigen presentation)를 통해 효과적으로 HCV 특이 T 림프구를 활성화시키며 간암세포주(huh7.5) 표면의 PD-L (program death ligand) 1 발현은 T림프구의 활성을 감소시켜 면역조절의 가능성이 있음을 시사하였다. 또한, HCV 특이 tetramer 반응은 T 림프구의 과도한 활성으로 자기사멸(apoptosis)의 경로에 있음을 caspase 3 활성으로 확인하였고, 역시 PD-L1의 발현이 T 림프구를 자기사멸(apoptosis)로부터 구제하여 caspase 3 활성이 감소하는 것을 확인하였다. 이는 PD-L1과 간성(liver) T 림프구 표면의 PD-1 결합이 T 림프구의 자기사멸을 막고, 또한 그 기능을 회복시켜 만성 C형 간염 치료에 응용될 수 있음을 시사한다.

• Restorative Dentistry and Endodontics
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• 제27권1호
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• pp.1-11
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• 2002

Immune responses associated with bacterial infection involve various inflammatory cells. Clinical symptoms and pathologic features are particularly influenced by the predominant cells Among inflammatory cells, T cells have the heterogenity. T cells may develop into the mature cells expressing the cell surface markers with different functions and T helper cells are categorized into Th1 and Th2 cells based on their different patterns of cytokine production. The objective of this study was to investigate the change of expression of surface markers on T cells and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. We experimentally induced pulpal inflammation in rat incisors by drilling without coolant and innoculated with Streptococcus mutans (S.M. group), Porphyromonas endodontalis (P.E. group), or only sterile cotton (control group). After 1, 2, and 5 days, mandibular incisors were extracted and the pulp tissues were extirpated The expressions of IL-2 recepters (CD25) and ICAM-1 (CD54) on CD4+ and CD8+ cells in the pulps were determined using a flow cytometer, and the concentration of IL-2, IFN-$\gamma$ and IL-4 was measured by enzyme-linked immunosorbent assay. The results were as follows: 1 In the S.M. group, CD4+ cells were more increased at 2nd day than 1st day and in the P.E. group, CD8+ cells were more increased at 2nd day than 1st day. 2. The percentages of CD4+, CD4+25+ and CD4+54+ cells were decreased in the pulp tissues at 5th day after irritation in all groups. 3. The ratios of CD4+/CD8+, CD4+/CD4+25+ and CD4+/CD4+54+ in the pulps at 2nd day after irritation by P. endodontalis were significantly lower than the other groups. 4. The higher concentrations of IFN-$\gamma$ than IL-4 in the pulps at 2nd day after irritation by P. endodontalis showed that T helper 1 reaction were predominant in the early stage of the pulpal inflammation induced by P. endodontalis. 5. The higher concentrations of IL-4 than IFN-$\gamma$ in the pulps at 1st day and 5th day after irritation by S. mutans were measured but the differences were not significant.

• Animal cells and systems
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• 제8권2호
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• pp.117-123
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• 2004

The purpose of this study was to analyze inhibitory effects of anti-4-1BB monoclonal antibody on melanoma metastasis The 4-1BB (CD137) T cell molecule is a member of the TNF receptor family and its activation by either 4-1BB ligand or antibody induces T cell activation and growth. In the present study, administration of anti-4-1BB mAb induced inhibition of melanoma metastasis. Agonistic anti-4-1BB mAb induced not only CD$8^+$4-1BBT cells but also CD$8^+$IFN-${\gamma}$$^{+}$ T cell population. In the presence of anti-CD3 antibody, lymphocytes produced high levels of IFN-${\gamma}$ and low levels of IL-4 in anti-4-1BB mAb treated group. Exposure of melanoma cells to IFN-${\gamma}$ induced expression of MHC-I molecules. Thus, the increase in number of CD$8^+$T cells and enhanced MHC-I expression on B16F10 cells by augmented IFN-${\gamma}$ production in response to anti-4-1BB mAb may result in suppression of tumor growth and metastasis.s.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• 대한예방한의학회지
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• 제5권1호
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• pp.103-115
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• 2001

Background : Gamisamryungbaekchul-san(加味蔘?白朮散) is a herbal medicine which has been used for the traditional therapeutic agent of augmentation of the spleen and reinforcement of the Qi. Objective : This Study was performed to investigate the effect of Gamisamryungbaekchul-san on the tumor and immune response in the moose B16 melanoma tumor model. Materials and Methods : The tumor was induced by subcutaneous inoculation of B16BL6 melanoma cells in the shaved dorsal region of mice. Mice were orally administered with Gamisamryungbaekchul-san extract(26.3mg/mouse) for 14days after inoculation. For making examination of antitumor effect, the Increase of life span, Tumor growth inhibition rate, change of body weight were measured and evaluated. For the immune response increasing effect, the percentage of T lymphocyte and B Lymphocyte in the peripheral blood, the percentage of CD4+ T-cell, CD8+ T-cell and CD4+/CD8+ ratio in the peripheral blood and spleen, interleukin-2 productivity were measured and evaluated. Results : Gamisamryungbaekchul-san showed 16.59% increase of life span, 31.64% tumor growth inhibition rate and increase of body weight. Gamisamryungbaekchul-san increased the percentage of T lymphocyte in the peripheral blood, CD4+ T cell percentage of peripheral blood and spleen, and Interleukin-2 productivity as compared with the Control group. Whereas Gamisamryungbaekchul-san had no effect on the percentage of B lymphocyte in the peripheral blood, the percentage of CD8+ T cell, CD4+/CD8+ T-cell ratio in both of peripheral blood and spleen as compared with the Control group. Conclusion : This study shows that Gamisamryungbaekchul-san has anti-tumor effects and immunoregulatory effects on the B16 melanoma tumor model. It is suggested that Gamisarmyungbaekchul-san could be a useful immunomodulator and anti-tumor agent.

• IMMUNE NETWORK
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• 제14권4호
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• pp.207-218
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• 2014

Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, ${\alpha}$-galactosylceramide (${\alpha}GC$) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific $CD8^+$ T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by ${\alpha}GC$ can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naïve mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after ${\alpha}GC$-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naïve and chronically infected mice. Similar to naïve B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 $CD8^+$ T cells in vivo, thereby allowing the proliferation of functional $CD8^+$ T cells. Importantly, when ${\alpha}GC$ and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific $CD8^+$ T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between ${\alpha}GC$-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.

• 대한의생명과학회지
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• 제2권2호
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• pp.167-174
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• 1996

알코올 중독자의 폐렴관리와 같은 건강관리에 필요한 비특이 면역력, 면역기능을 측정하기 위하여 알코올 중독 의존형으로 입원한 신,구환자군에 대하여 다음과 같은 결과를 얻었다. 대조군에 대한 알코올 중독증은 MCV, 혈당, $\gamma$GTP를 이용한 생물학적 측정 결과에 의하여 확인하였으며, 기타 측정 항목은 대조군과 유사한 결과를 나타내었다. 림프구 아형 분석 결과 대조군은 한국인 참고치와 매우 유사하였으며, 실험군 CD4+를 제외한 CD3+, CD8+, CD19+이 감소되었고, CD4+/CD8+비율은 통계적으로 유의하게 증가되어 있음을 알 수 있었다. 따라서 실험군의 면역기능과 림프구 증식능은 대조군에 비하여 현저하게 저하되었으며, 탐식세포 탐식능 및 유주능도 대조군에 비하여 현저하게 감소되었다. 탐식세포의 유주능과 CD4+의 증가, CD4+/CD8+비율의 증가와 PHA에 의한 림프구 증식능의 감소 및 CD3+, CD19+ 감소등은 상호관련성을 가지고 일치된 결과를 보여 대조군에 비하여 현저하게 저하된 탐식세포의 탐식기능과 함께 알코올 중독자의 비특이 면역계, 면역기능이 현저하게 저하되어 있음을 알 수 있었다. 그러나 알코올 중독 의존형으로 입원한 신,구환자간의 비교 분석 결과 총단백질, 혈색소, 림프구 증식능, 탐식세포 탐식능, 유주능에서 신환자군에 비하여 구환자군이 대조군에 다소 근접되어가는 결과로부터 치료에 따라 숙주의 세포성, 체액성 면역기능이 회복되어가고 있음을 알 수 있었다. 또한 결과 알코올중독자의 비특이적 면역능의 측정을 위한 탐식세포 탐식능, 유주능은 숙주, 미생물측의 활성화 자극인자가 모두 포함된 phagocytic plaque film법에 의하여 측정함이 의의 있는 평가를 할 수 있을 것으로 보며, CD4+/CD8+ 림프구 아형 비율을 이용한 면역기능의 측정은 알코올 중독자의 건강 관리를 위한 면역력 측정에 유용한 방법이라고 생각된다사이에서는 차이를 인정할 수 없었다. 그러나 25개월 운동군은 대조군에 비하여 유의한 차이로 감소하였다. 연령증가에 따른 사립체 내막 표면밀도와 사립체수는 대조군과 운동군 사이에는 유의한 변화는 없었다. 본 연구의 성적을 검토한 결과 젊은층(3개월군)과 중령층(10개월군)의 횐 쥐에서는 반복된 지구력운동이 심장에 미치는 역효과를 인정할 수 없었으며 젊은 층의 횐 쥐에서는 오히려 심장기능 강화를 보이는 경향이 나타났으며, 노화층(20개월군)에서 운동군에서는 스트레스로 작용하여 심장기능의 저하를 초래하였다고 생각된다.서 낭송된다. 그러나 이 연구의 기본은 시인과 독자의 율형(Metrical Pattern)에 대한 의식과 의도(intention)가 전제된다. 이것은 이 연구의 문제임과 동시에 장점이다. 시율의 분석은 보는 율형이 아니라 읽고 낭송하는 율형으로 분석되어야 함을 보여 준 것이 이 연구의 기여이다.ight reduction but the rapid weight gain was noticed right after the diets ceased.나 인과 질소 평형에는 큰 영향을 미치지 않았다.더덕은 20(種)이었다. 9. Trans-2-hexanol은 야생(野生)더덕의 자생지(自生地) 재배(栽培)에서 피이크 면적(面積) 당(當) 50.3%, 재배지(栽培地)에서 피이크 면적(面積) 당(當) 43.3%를 보였으며 amylalcohol, furfuryl acetate, 2-methoxy-4-vinyl phenol(MVP)는 재배(栽培)더덕에서만 확인(確認)되었다.는 KI, BMI와 유의적인 양의 상관관계를 보였고 (p<0.01), HCL-C은 비체중, BMI, LBM, TBM와 유의적인 음의 상관관계를 보였으며, (p<0.01), KI, SBP와도 음의 상관관계를 보였다. (p<0.05), LCL-C는 KI와 유의적이인 양의 상관관계를 나타내었으며 (p<0.01) BF%, TBF, BMI와도

• Journal of Microbiology and Biotechnology
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• 제30권3호
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• pp.439-447
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• 2020

We investigated the immune restoration activity of Undaria pinnatifida fucoidan-rich extract in cyclophosphamide-induced immunosuppressed mice. C57BL/6 mice were intraperitoneally injected with 80 mg/kg of cyclophosphamide (CP) and orally administered with either drinking water (DW), red ginseng extract (RG), or one of three different doses of Undaria pinnatifida fucoidan-rich extract (DSU02 50, 100, and 150 mg/kg). After 14 days, liver, spleen, and whole blood were isolated from each animal. The frequencies of NK and CD³⁺, CD⁴⁺, and CD⁸⁺ T cells were significantly increased in splenocytes isolated from the DSU02 100 mg/kg and DSU02 150 mg/kg groups (NK1.1+, 5.4% or 4.9% vs 3.8%; CD³⁺, 39.3% or 37.9% vs 32.3%; CD4+, 22% or 20.2% vs 17.4%; CD8+, 12.7% or 11.6% vs 10.1%). NK cytotoxicity was enhanced in the DSU02-fed groups at all doses (CP-treated DW, 93.4%; RG, 107.2%; DSU02 50, 107.3%; DSU02 100, 107.3%; DSU02 150, 107.1%), and the proliferation of T cells (CD³⁺, CD⁴⁺, and CD⁸⁺) was also greater in the DSU02 100 mg/kg and DSU02 150 mg/kg administered groups compared with the unfed group. Plasma concentrations of TNF-α, IgM, and total IgG from the DSU02 150 mg/kg group were also significantly higher compared with the other groups (TNF-α: CP-treated DW - 21.5 pg/ml, DSU02 150 - 47.1 pg/ml; IgM: CP-treated DW - 82.9 ng/ml, DSU02 150 - 110.8 ng/ml; total IgG: CP-treated DW - 114.4 ng/ml, DSU02 150 - 162.7 ng/ml). We suggest that Undaria pinnatifida fucoidan-rich extract could be a promising candidate for a marine natural immune stimulator.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5909-5913
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• 2012

Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.