• IMMUNE NETWORK
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• v.23 no.1
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• pp.3.1-3.14
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• 2023

Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

• Genomics & Informatics
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• v.21 no.2
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• pp.18.1-18.11
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• 2023

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55⁺) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

• 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.

• 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.

• 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.

• 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.

• 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.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.299-308
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• 2022

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.1
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• pp.227-252
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• 2007

Objectives : In order to investigate the effect of Bobitang on SD rats with deteriorated immunity caused by methotrexate. Methods : The test sample were dosed once a day for 14 days by gastric gavage at a dosage 1,000, 500 and $250mg/kg/10m{\ell}$ from 2 days after last MTX-dosing, and the changes on body weight and gains, spleen weight and total blood leukocyte numbers, total lymphocyte numbers, the percentage of B-cell, T-cell, CD3+CD4+ T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the blood and spleen were observed. Results : The changes on body weight gains, the spleen weight, the total blood leukocyte numbers, the total lymphocyte numbers in the blood and spleen, the ratio of T-cell in the blood and spleen, the ratio of CD3+CD4+ T-cell in the blood and spleen were increased significantly in BBT Extracts groups as compared with control group. The ratio of B-cell in the blood and spleen was not increased significantly in BBT Extracts groups as compared with control group. The percentage of CD3+CD8+ T-cell in the blood and spleen was decreased significantly in BBT Extracts groups as compared with control group. The ratio of CD4+/CD8+ T-cell in blood and spleen was increased significantly in BBT Extracts group as compared with control group. Conclusions : According to the above results, Bobi-Tang has an effect of increasing immune responses on SD rats with deteriorated immunity caused by methotrexate.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.693-700
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• 2002

SCRT (Sochungyong-tang) has been used for immune disease in human. The purpose of this study was effect of Helper T cell, major regulator of immune system. Spleen cell from 8 week BALB/c mice were cultured in SCRT containing medium without activation for 48 h. The MTS assay and flow cytometry revealed that SCRT treated Iympocyte were non-effect in percentage of CD4+ T cell. Subsequently CD4+ T cell were isolated and cultured in SCRT containing medium. SCRT were non-effective on CD4+ T cell without any involvement of APC. In order to evaluate the direct effect of SCRT on Helper T cell, CD4+ T cell isolated after 48 h of culture in SCRT containing medium and activated with and without anti-CD3/anti-CD28 activation for 48 h. A lower level of CD69 was observed in SCRT treated cells in flow cytometry analysis. Subsequently Using RT-PCR analysis the expression of mRNA for IL-2, INF-γ are upregulated and, IL-4 is downregulated in CD4 T cell. The result suggests that SCRT makes Th1 significantly increased and Th2 relatively inhibited. The results suggest that SCRT potentiate Th1 cell and decrease Th2 development at the same time, which is believed to be bemeficial for IgE-mediated responses.