• Title, Summary, Keyword: T -cell

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Mechanism of T cell exhaustion in a chronic environment

  • Jin, Hyun-Tak;Jeong, Yun-Hee;Park, Hyo-Jin;Ha, Sang-Jun
    • BMB Reports
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    • v.44 no.4
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    • pp.217-231
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    • 2011
  • T cell exhaustion develops under conditions of antigen-persistence caused by infection with various chronic pathogens, such as human immunodeficiency virus (HIV) and myco-bacterium tuberculosis (TB), or by the development of cancer. T cell exhaustion is characterized by stepwise and progressive loss of T cell function, which is probably the main reason for the failed immunological control of chronic pathogens and cancers. Recent observations have detailed some of the intrinsic and extrinsic factors that influence the severity of T cell exhaustion. Duration and magnitude of antigenic activation of T cells might be associated with up-regulation of inhibitory receptors, which is a major intrinsic factor of T cell exhaustion. Extrinsic factors might include the production of suppressive cytokines, T cell priming by either non-professional antigenpresenting cells (APCs) or tolerogenic dendritic cells (DCs), and alteration of regulatory T (Treg) cells. Further investigation of the cellular and molecular processes behind the development of T cell exhaustion can reveal therapeutic targets and strategies for the treatment of chronic infections and cancers. Here, we report the properties and the mechanisms of T cell exhaustion in a chronic environment.

Role for CD40 and CD40L Expression in Generating CD8 T Cell Response to Minor Histcompatibility Antigen, H60

  • Jung, Kyoung-Min;Choi, Eun-Young
    • IMMUNE NETWORK
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    • v.7 no.4
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    • pp.173-178
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    • 2007
  • Background: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. Methods: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. Results: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of $CD40^{+/+}$ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with $CD40^{+/+}$ CD4 T cells. Adoptive transfer of $CD40L^{+/+}$ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of $CD40L^{+/+}$ CD4 T cells was required even for memory CD8 T cells response to H60. Conclusion: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naive and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

Effects of FUll-FEat Flax Seed, $\alpha$-Tocopherol and Selenium on the Expression of cell Surface Antigen of Broiler Chickens (아마종실과 $\alpha$-Tocopherol, 셀레늄 급여가 육계의 세포표면항원 발현에 미치는 영향)

  • 안종남;채현석;문진산;김동운;권명상;박병성
    • Korean Journal of Poultry Science
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    • v.28 no.3
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    • pp.231-237
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    • 2001
  • To examine the effects of feed additives on the expression of perpheral blood cell surface molecules, phagocytosis and antigen specific antibody formation, broilers were randomly assigned to $T_{1}$ , $T_{2}$ , $T_{3}$ , and $T_{4}$ groups. $T_{1}$ group was fed diet without any additives for 13 weeks, $T_{2}$ was fed diet with full fat flax, $T_{3}$ was fed diet with full fat flax containing $\alpha$-tocopherol, and $T_{4}$ was fed diet with full- fat flax containing $\alpha$-tocopherol and selenium. Since 5 weeks feeding the data were examined by flow cytometry using a panel of monoclonal antibodies. The expression of monocyte in all treated groups was significantly increased, in which the ratio of expression in $T_{3}$ group was especially evident. B cell expression of all treated groups was increased more than 2 fold. The expression of CD4+(helper T cell) cell and CD8+(cytotox$ic^pressor T cell) cell of all treated groups also was increased.ed.

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Cell-cell Adhesion of Jurkat T Cells Induced by CD29 and CD98 Activation and its Application (CD29 및 CD98 활성 매개에 의한 Jurkat T 세포의 유착과 그 활용)

  • Kim, Byung-Hun;Cho, Jae-Youl
    • YAKHAK HOEJI
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    • v.53 no.3
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    • pp.119-124
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    • 2009
  • Cell-cell adhesion managed by various adhesion molecules plays an important role in regulating functional activation of cells. This event mediates attachment of inflammatory cells to endothelial cells, interaction of antigen-presenting cells with T cells and metastatic adherence of cancer cells to epithelial tissue cells. Therefore, this cellular response is considered as one of therapeutic target to treat various cancers and inflammatory diseases. To develop proper model for evaluation of functional activation of adhesion molecules, the ability of U937 and Jurkat T cells responsive to various adhesion inducers such as phorbal-12-myristate-13-acetate (PMA), staurosporin and monoclonal antibodies to CD29, CD43 and CD98 was investigated using quantitative cell-cell adhesion assay. U937 cells made more cell-cell clusters by the treatment of antibodies to CD29 and CD43 than Jurkat T cells, while Jurkat T cells exhibited increased cell-cell adhesion ability in CD98 antibody treatment. In agreement, the surface levels of CD29 and CD98 were highly observed in U937 and Jurkat T cells, respectively. Therefore, our data suggest that Jurkat T and U937 cells can be used for model system to evaluate functional activation of adhesion molecules such as CD29 and CD98.

TAGLN2-mediated actin stabilization at the immunological synapse: implication for cytotoxic T cell control of target cells

  • Na, Bo-Ra;Jun, Chang-Duk
    • BMB Reports
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    • v.48 no.7
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    • pp.369-370
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    • 2015
  • Actin dynamics is critical for the formation and sustainment of the immunological synapse (IS) during T cell interaction with antigen-presenting cells (APC). Thus, many actin regulating proteins are involved in spatial and temporal actin remodeling at the IS. However, little is known whether or how actin stabilizing protein controls IS and the consequent T cell functions. TAGLN2 − an actin-binding protein predominantly expressed in T cells − displays a novel function to stabilize cortical F-actin, thereby augmenting F-actin contents at the IS, and acquiring leukocyte function-associated antigen-1 activation following T cell activation. TAGLN2 also competes with cofilin to protect F-actin in vitro and in vivo. During cytotoxic T cell interaction with cancer cells, the expression level of TAGLN2 at the IS correlates with the T cell adhesion to target cancer cells and production of lytic granules such as granzyme B and perforin, thus expressing cytotoxic T cell function. These findings identify a novel function for TAGLN2 as an actin stabilizing protein that is essential for stable immunological synapse formation, thereby regulating T cell immunity. [BMB Reports 2015; 48(7): 369-370]

Effect of Baicalein on t-Butylhydroperoxide-Induced Cell Injury in Renal Tubular Epithelial Cells

  • Soon-Bee Jung
    • Biomedical Science Letters
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    • v.9 no.4
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    • pp.189-193
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    • 2003
  • This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

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The Effect of Hwanggigunjung-tang on Imunosuppression induced by Methotrexate in Rat (황기건중탕(黃芪建中湯)이 Methotrexate로 유도된 흰쥐의 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Baek, Jung-Han;Koo, Jin-Suk
    • The Journal of Pediatrics of Korean Medicine
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    • v.18 no.1
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    • pp.27-48
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    • 2004
  • Objective: The purpose of this study was to investigate the effect of Hwanggigunjungtang(HGT) on white rats with deteriorated immunity caused by methotrexate. Methods: First, methotrexate was fed to the white rats once a day for 4 days. After the immune responses of the rats are deteriorated, dried extracts of HGT mixed in water was fed to the rats once a day for 14 days. And then we measured the percentage of B-cell and T-cell in peripheral blood, the percentage of CD3+CD4+ T-cell and CD3+CD8+ T-cell of blood sampled from spleen and peripheral region. Results: The percentage of B-cell of peripheral blood was not different statistically. The percentage of T-cell of peripheral blood was increased significantly in HGT group as compared with control group. The percentage of CD3+CD4+ T-cell of peripheral blood was increased significantly in HGT group as compared with control group. The percentage of CD3+CD8+ T-cell of peripheral blood was decreased in HGT group as compared with control group. The percentage of CD3+CD4+ T-cell of spleen was increased significantly in HGT group as compared with control group. The percentage of CD3+CD8+ T-cell of spleen was not different statistically. Conclusion: According to the above results, HGT has an effect of increasing immune responses on white rats with deteriorated immunity caused by methotrexate.

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Functional Understating of Fibroblastic Reticular Cell within Lymph Node Stroma (림프절 스토로마 내의 fibroblastic reticular cell의 기능 이해)

  • So, Deuk Won;Ryu, Sul Hwa;Lee, Jong-Hwan
    • Journal of Life Science
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    • v.23 no.11
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    • pp.1409-1414
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    • 2013
  • Lymph node (LN) is the sites where mature lymphocytes become stimulated to respond to invading pathogens in the body. Lymphocytes screen the surfaces of pathogen-carrying antigen-presenting cells for cognate antigens, while moving along stromal structural back bone. Fibroblastic reticular cells (FRC) is stromal cell forming the 3 dimensional structure networks of the T cell rich zones in LN, and provide a guidance path for immigrating T lymphocytes. In these cooperative environments, the cell to cell bidirectional interactions between FRC and T cells in LN are therefore essential to the normal functioning of these tissues. Not only do FRCs physically construct LN architecture but they are essential for regulating T cell biology within these domains. FRC interact closely with T lymphocytes, is providing scaffolds, secreting soluble factors including cytokine in which FRCs influence T cell immune response. More recently, FRC have been found to induce peripheral T cell tolerance and regulate the extent to which newly activated T cells proliferate within LN. Thus, FRC-T cell crosstalk has important consequences for regulating immune cell function within LN. In addition, FRC have profound effects on innate immune response by secreting anti-microbial peptides and complement, etc in the inflammatory milieu. In summary, we propose a model in which FRC engage in a bidirectional touch to increase the T cell biological efficiency between FRC and T cells. This collaborative feedback loop may help to maintain tissue function during inflammation response.

Comparison Analysis of Immune Cells between CT26 Tumor Bearing Mice and Normal Mice

  • Lee, Na Kyung;Kim, Hong Sung
    • 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.

Anti-proliferative Activity of T-bet

  • Oh, Yeon Ji;Shin, Ji Hyun;Won, Hee Yeon;Hwang, Eun Sook
    • IMMUNE NETWORK
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    • v.15 no.4
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    • pp.199-205
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    • 2015
  • T-bet is a critical transcription factor that regulates differentiation of Th1 cells from $CD4^+$ precursor cells. Since T-bet directly binds to the promoter of the IFN-${\gamma}$ gene and activates its transcription, T-bet deficiency impairs IFN-${\gamma}$ production in Th1 cells. Interestingly, T-bet-deficient Th cells also display substantially augmented the production of IL-2, a T cell growth factor. Exogenous expression of T-bet in T-bet deficient Th cells rescued the IFN-${\gamma}$ production and suppressed IL-2 expression. IFN-${\gamma}$ and IL-2 reciprocally regulate Th cell proliferation following TCR stimulation. Therefore, we examined the effect of T-bet on Th cell proliferation and found that T-bet deficiency significantly enhanced Th cell proliferation under non-skewing, Th1-skewing, and Th2-skewing conditions. By using IFN-${\gamma}$-null mice to eliminate the anti-proliferative effect of IFN-${\gamma}$, T-bet deficiency still enhanced Th cell proliferation under both Th1- and Th2-skewing conditions. Since the anti-proliferative activity of T-bet may be influenced by IL-2 suppression in Th cells, we examined whether T-bet modulates IL-2-independent cell proliferation in a non-T cell population. We demonstrated that T-bet expression induced by ecdysone treatment in human embryonic kidney (HEK) cells increased IFN-${\gamma}$ promoter activity in a dose dependent manner, and sustained T-bet expression considerably decreased cell proliferation in HEK cells. Although the molecular mechanisms underlying anti-proliferative activity of T-bet remain to be elucidated, T-bet may directly suppress cell proliferation in an IFN-${\gamma}$- or an IL-2-independent manner.