• Title/Summary/Keyword: T Cell Population

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Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

  • Lee, Jung-Mi;Seo, Jeong-Hwan;Kim, Yeon-Jeong;Kim, Yun-Sun;Ko, Hyun-Jeong;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.10 no.3
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    • pp.104-108
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    • 2010
  • CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress $CD4^+$ T cells, ameliorating autoimmune diseases, whereas it induces activation of $CD8^+$ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect $CD11b^+Gr-1^+$ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased $CD11b^+Gr-1^+$ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both $CD8^+$ T cells and $CD4^+$ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce $CD11b^+Gr-1^+$ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.

Expression of Epstein-Barr Virus Gene and Clonality of Infiltrated T Lymphocytes in Epstein-Barr Virus-associated Gastric Carcinoma

  • Lee, Jae-Myun;Kim, Ho-Guen;Noh, Sung-Hoon;Lee, Won-Young;Kim, Se-Jong;Park, Jeon-Han
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.50-58
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    • 2011
  • Background: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. Methods: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. Results: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. $CD8^+$ T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR $V{\beta}$ CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. Conclusion: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.

THE SOJOURN TIME AND RELATED CHARACTERISTICS OF THE AGE-DEPENDENT BRANCHING PROCESS

  • Kumar, B.-Krishba;Vijayakumar, A.
    • Journal of applied mathematics & informatics
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    • v.14 no.1_2
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    • pp.157-172
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    • 2004
  • An age-dependent branching process where disasters occur as a renewal process leading to annihilation or survival of all the cells, is considered. For such a process, the total mean sojourn time of all the cells in the system is analysed using the regeneration point technique. The mean number of cells which die in time t and its asymptotic behaviour are discussed. When the disasters arrival as a Poisson process and the lifetime of the cells follows exponential distribution, elegant inter- relationships are found among the means of (i) the total number of cells which die in time t (ii) the total sojourn time of all cells in the system upto time t and (iii) the number of living cells at time t. Some of the existing results are deduced as special cases for related processes.

Effects of Walgookwhanhab-Bojoongikgitang administration on immune-function in Balb/c mice stressed by electric footshock (월국환합보중익기탕(越鞠丸合補中益氣湯)이 전기자극(電氣刺戟)스트레스를 받은 mouse의 면역기능(免疫機能)에 미치는 영향(影響))

  • Kwon, Tae-Sig;Lee, Suk-Kyeong;Gu, Byung-Su
    • The Journal of Dong Guk Oriental Medicine
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    • v.9
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    • pp.51-71
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    • 2000
  • The present experiments were designed to study the influence of WalgookwhanhabBojoongikgitang on immune functions of Balb/c mice under stress condition. WalgookwhanhabBojoongikgitang was orally administered to the mice for 15 days. On the 10th day the mice were immunized with sheep red blood cells (SRBC) and then subjected to electric footshock for 5 days (2 sessions a day, 11 footshocks a 31 min-session). The immune responses to SRBC were determined by means of hemagglutination and BIT cell populations in the spleen were studied by FACS analysis on the 16th day. The results were as follows. 1. After electric footshock, IDlce became sluggish and crowded to one side of the cage. Increased antibody titer for SRBC, increased B cell population, and decreased T cell population in the spleen were also observed. These results confirm that electric footshock caused stress inducing immunological and behavioral changes in Balblc mice. 2. Walgookwhanhab-Bojoongikgitang administration significantly antagonized the effect of electric footshock on the antibody titer for SRBC. As a result, antibody titers for SRBC in the mice treated with Walgookwhanga-Bojoongikgitang were maintained at the similar levels as those of control group mice even after the electric foots hock. 3. Walgookwhanhab-Bojoongikgitang administration also antagonized the effect of electric footshock on the BIT populations in spleen. As a result, Band T populations in the mice treated with Walgookwhanhab-Bojoongikgitang were maintained at the similar levels as in the control group mice even after the electric footshock. Taken together, Walgookwhanhab-Bojoongikgitang seem to help Balb/c mIce to maintain their humoral immune response and immune cell populations at a normal range under the stress conditions, suggesting its possible therapeutic use as a immune function modulator.

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Differential Signaling via Tumor Necrosis Factor-Associated Factors (TRAFs) by CD27 and CD40 in Mouse B Cells

  • Woo, So-Youn;Park, Hae-Kyung;Bishop, Gail A.
    • IMMUNE NETWORK
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    • v.4 no.3
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    • pp.143-154
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    • 2004
  • Background: CD27 is recently known as a memory B cell marker and is mainly expressed in activated T cells, some B cell population and NK cells. CD27 is a member of tumor necrosis factor receptor family. Like CD40 molecule, CD27 has (P/S/T/A) X(Q/E)E motif for interacting with TNF receptor-associated factors (TRAFs), and TRAF2 and TRAF5 bindings to CD27 in 293T cells were reported. Methods: To investigate the CD27 signaling effect in B cells, human CD40 extracellular domain containing mouse CD27 cytoplamic domain construct (hCD40-mCD27) was transfected into mouse B cell line CH12.LX and M12.4.1. Results: Through the stimulation of hCD40-mCD27 molecule via anti-human CD40 antibody or CD154 ligation, expression of CD11a, CD23, CD54, CD70 and CD80 were increased and secretion of IgM was induced, which were comparable to the effect of CD40 stimulation. TRAF2 and TRAF3 were recruited into lipid-enriched membrane raft and were bound to CD27 in M12.4.1 cells. CD27 stimulation, however, did not increase TRAF2 or TRAF3 degradation. Conclusion: In contrast to CD40 signaling pathway, TRAF2 and TRAF3 degradation was not observed after CD27 stimulation and it might contribute to prolonged B cell activation through CD27 signaling.

Effects of Orostachys Japhonicus Herbal-Acupuncture on Transferred Hepatic Cancer of Mouse Induced by Colon26-L5 Human Colon Cancer Cells (와송(瓦松) 약침(藥鍼)이 mouse의 간전이 암모델에 미치는 영향)

  • Sohn, Seong-Hyoun;Park, Hee-Soo
    • 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.

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Lack of Association of a Common Polymorphism in the 3'-UTR of Interleukin 8 with Non Small Cell Lung Cancer in Kashmir

  • Bhat, Imtiyaz Ahmad;Pandith, Arshid A.;Bhat, Bashir A.;Naykoo, Niyaz A.;Qasim, Iqbal;Rasool, Roohi;Aziz, Sheik Aejaz;Shah, Zafar Amin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4403-4408
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    • 2013
  • Background: Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. Materials and Methods: One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. Results: The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. Conclusions: In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.

Flow cytometric analysis of apoptosis in mouse thymocytes by galectin-3 (유세포 분석기를 이용한 galectin-3에 의해 유도된 흉선세포의 apoptosis 분석)

  • Kim, Tae-jung;Woo, Hee-jong
    • Korean Journal of Veterinary Research
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    • v.39 no.6
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    • pp.1112-1118
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    • 1999
  • Galectin-3 plays an important role in cell development, differentiation and cancer metastasis, including cell-cell/extracellular matrix (ECM) interactions and is supposed to have an effect of apoptosis on T-cells in thymic clonal selection. In this study, to know the effect of galectin-3 on thymocyte development, we used recombinant human galectin-3 (rHgal-3) from Escherichia coli, JM105, which was inserted with human gal-3 gene-transformed plasmid vector (prGal-3) to express human galectin-3. Expressed rHgal-3 was confirmed by western blot using the culture supernant of hybridoma (M3/38) producing monoclonal antibody to human galectin-3. Sepharose gel affinity chromatography was used to purify the expressed rHgal-3. Thymocytes and hepatocytes from 6-week-old male BALB/c mice were incubated with rHgal-3 and showed marked increase of apoptotic population on analysis using flow cytometry with 7-AAD in a dosedependent manner. However, rHgal-3 failed to induce apoptosis on hepatocytes. Interestingly, this apoptotic effect was not inhibited by lactose, a specific lectin domain inhibitor. From these results, we concluded that extrinsic -3 induces apoptosis on mouse thymocytes, and galectin-3 may have an apoptotic effect on T-cells in thymic clonal selection.

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Bioassay-guided Isolation of Deoxypodophyllotoxin, the Cytotoxic Constituent of Juniperus chinensis

  • Ali, A.M.;Intan-Safinar, I.;Mackeen, M.M.;El-Sharkawy, S.H.;Takahata, K.;Kanzaki, H.;Kawazu, K.
    • Natural Product Sciences
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    • v.4 no.3
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    • pp.180-183
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    • 1998
  • The ethanol extract from the leaves of Juniperus chinensis was found to be cytotoxic towards HeLa cells. Bioassay-guided fractionation of the EtOAc soluble faction directed by the microtitration cytotoxic assay revealed that the cytotoxic compound was deoxypodophyllotoxin. All the tumour cell lines tested (KU8112F-chronic mylogeneous leukemia, TK 10-renal carcinoma, UACC 62-melanoma and CEM-SS-T-lymphoblastic leukemia) were found to be susceptible to deoxypodophyllotoxin, however, the minimum effective concentration (MEC) required to reduce the cell population by 100 percent was different between cell lines.

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GM-CSF Grown Bone Marrow Derived Cells Are Composed of Phenotypically Different Dendritic Cells and Macrophages

  • Na, Yi Rang;Jung, Daun;Gu, Gyo Jeong;Seok, Seung Hyeok
    • Molecules and Cells
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    • v.39 no.10
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    • pp.734-741
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    • 2016
  • Granulocyte-macrophage colony stimulating factor (GM-CSF) has a role in inducing emergency hematopoiesis upon exposure to inflammatory stimuli. Although GM-CSF generated murine bone marrow derived cells have been widely used as macrophages or dendritic cells in research, the exact characteristics of each cell population have not yet been defined. Here we discriminated GM-CSF grown bone marrow derived macrophages (GM-BMMs) from dendritic cells (GM-BMDCs) in several criteria. After C57BL/6J mice bone marrow cell culture for 7 days with GM-CSF supplementation, two main populations were observed in the attached cells based on MHCII and F4/80 marker expressions. GM-BMMs had $MHCII^{low}F4/80^{high}$ as well as $CD11c^+CD11b^{high}CD80^-CD64^+MerTK^+$ phenotypes. In contrast, GM-BMDCs had $MHCII^{high}F4/80^{low}$ and $CD11c^{high}CD8{\alpha}^-CD11b^+CD80^+CD64^-MerTK^{low}$ phenotypes. Interestingly, the GM-BMM population increased but GM-BMDCs decreased in a GM-CSF dose-dependent manner. Functionally, GM-BMMs showed extremely high phagocytic abilities and produced higher IL-10 upon LPS stimulation. GM-BMDCs, however, could not phagocytose as well, but were efficient at producing $TNF{\alpha}$, $IL-1{\beta}$, IL-12p70 and IL-6 as well as inducing T cell proliferation. Finally, whole transcriptome analysis revealed that GM-BMMs and GM-BMDCs are overlap with in vivo resident macrophages and dendritic cells, respectively. Taken together, our study shows the heterogeneicity of GM-CSF derived cell populations, and specifically characterizes GM-CSF derived macrophages compared to dendritic cells.