• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• BMB Reports
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• v.50 no.9
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• pp.472-477
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• 2017

The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed $CD4^+$ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple Maf-recognition element-like sites on the interleukin-2 proximal promoter in a manner competitive with AP-1, and thereby represses AP-1-driven induction of interleukin-2 transcription. Thus, this study demonstrates that Bach2 is a direct repressor of the interleukin-2 gene in $CD4^+$ T cells during the immediate early phase of AP-driven activation, thereby playing an important role in the maintenance of immune quiescence in the steady state.

• Journal of Animal Science and Technology
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• v.64 no.5
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• pp.922-936
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• 2022

5-Hydroxytryptamine (5-HT), a monoamine, as a local regulator in the mammary gland is a chemical signal produced by the mammary epithelium cell. In cows, studies have shown that 5-HT is associated with epithelial cell apoptosis during the degenerative phase of the mammary gland. However, studies in other tissues have shown that 5-HT can effectively promote cell viability. Whether 5-HT could have an effect on mammary cell viability in dairy cows is still unknown. The purpose of this study was to determine: (1) effect of 5-HT on the viability of bovine mammary epithelial cells and its related signaling pathways, (2) interaction between prolactin (PRL) and 5-HT on the cell viability. The bovine mammary alveolar cell-T (MAC-T) were cultured with different concentrations of 5-HT for 12, 24, 48 or 72 hours, and then were assayed using cell counting kit-8, polymerase chain reaction (PCR) and immunobloting. The results suggested that 20 μM 5-HT treatment for 12 or 24 h promote cell viability, which was mainly induced by the activation of 5-HT receptor (5-HTR) 1B and 4, because the increase caused by 5-HT vanished when 5-HTR 1B and 4 was blocked by SB224289 and SB204070. And protein expression of mammalian target of rapamycin (mTOR), eukaryotic translation elongation factor 2 (eEF2), janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were decreased after blocking 5-HT 1B and 4 receptors. When MAC-T cells were treated with 5-HT and PRL simultaneously for 24 h, both the cell viability and the level of mTOR protein were significantly higher than that cultured with 5-HT or PRL alone. In conclusion, our study suggested that 5-HT promotes the viability of MAC-T cells by 5-HTR 1B and/or 4. Furthermore, there is a reciprocal relationship between PRL and 5-HT.

• Animal cells and systems
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• v.4 no.4
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• pp.381-388
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• 2000

Using a murine T cell hybridoma, activation-induced cell death (AICD) was studied. As an in vitro model system for the AICD, 1 cell hybridoma expressing TCR/CD3 complex was incubated onto the immobilized purified anti-CD3 antibody. The immobilized anti-CD3 antibody induced AICD effectively up to 40%. At 1-100 $\mu$M range of SNP, an exogenous source of nitric oxide (NO), the cell proliferation was not affected, but at 1 mM SNP, cell proliferation was significantly reduced. The AICD of T cell hybridoma was inhibited by exogenous NO at non-cytotoxic concentration, In the cells undergoing AICD, the expressions of caspase-3 and FasL were detected, but not iNOS. Similar result was recognized in the apoptosis induced by dexamethasone, an apoptosis-inducing agent. However, the conversion from the inactive form of caspase-3 (32 kDa) to the active form (17 kDa) was significantly reduced in the cells in AICD induced by anti-CD3 antibody, With the result of increased PARP cleavage in the cells, we propose that another PARP cleavage pathway not involving caspase-3 may function in the anti-CD3 antibody induced AICD in the T cell hybridoma.

• IMMUNE NETWORK
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• v.14 no.4
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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.

• Parasites, Hosts and Diseases
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• v.31 no.1
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• pp.31-36
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• 1993

This study was performed to evaluate differences of T cell subsets according to the injection period of recombinant mouse $interferon-{\gamma}{\;}(IFN-{\gamma}$ in acute Toxoplasma gondii infection. Each mouse was infected intraperitoneally with 100 cysts of Beverley strain T. gondii, and injuten with $5{\;}{\times}{\;}10^4$ units of $IFN-{\gamma}$ every other day two tares. The percentage of Thy-1, 2 cells and L3T4/Ly-2 cell ratio were significantly increased in the mice that received two doses of $IFN-{\gamma}$ on days 2 and 0 before infection, or days 0 and 2 after infection. The percentage of Ly-2 cells decreased in the $IFN-{\gamma}$ injected groups at th\ulcorner 3rd and 4th week after infection. The results suggest that administration of $IFN-{\gamma}$ to T gonnii-infected mice improves the changed population of T cell subsets to a normal state, especially when $IFN-{\gamma}$ was infected just after the infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.580-585
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• 2004

BJYGC is often clinically used as a treatment of allergic rhinitis. This study was aimed to find out the effect BJYGC would have on the helper T cell, and how it can promote the subsets of helper T cells to regain their balance that they lost due to immunological diseases. Splenocytes were prepared from BALB/c mice was cultured without stimulation in the presence of BJYGC for 48 hr. The viability of CD4 T cells from Balb/c mouse were measured at various concentrations of BJYGC using the MTS assay. It was somewhat increased up to concentration of 400 ㎍/ml, but did not show any significant difference. Proliferation was measured using the MTS assay, CD4 Th cells were stimulated with anti-CD3/28 in the presence of BJYGC for 48 hr. As evidence for rapid T cell activation, CD25 expression by flow cytometry was evaluated at 10, 50, 100 and 200 ㎍/㎖ of BJYGC. Th cell differentiation experiments were performed to examine whether BJYGC can affect the Th polarization process. CD4 T cells were activated in culture under neutral, Th1-polarized or Th2-polarized conditions in the presence of BJYGC at 10, 100 and 200 ㎍/㎖. Cytokine production was measured by ELISA. This experiment proved that BJYGC could inhibit the secretion of both IL-4 and IFN-γ in neutral condition and polarized condition, too. Considering that BJYGC shows an excellent effect on treating allergies, the author can conclude that its pharmacological action may be associated with decreased IL-4 and, it may also regulate IFN-γ depending the host's need. Also, it was discovered that Th1 cell was pathologic in chronic inflammatory tissue specific diseases, such as insulin dependent diabetes mellitus, multiple sclerosis, RA, and uveitis. We are counting on the BJYGC to be able to control the tendency of Th1 cell predominancy in an immune reaction.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.4.1-4.22
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• 2022

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.801-809
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• 2002

CSBHT is known to improve immunological response in mice and humans. In this study, CSBHT effect was examined in the context of CD4+ T cells' survival and TCR/CD3 induced activation responses. Spleen cells from 8 week BALB/c mice were cultured in CSBHT containing medium without activation for 24, 48 hr. The MTS assay and revealed that CSBHT did not stimulate spleen lymphocytes as mitogen. Spleen lymphocytes were treated with anti-CD3e/anti-CD28 antibodies for 48hr. Flow cytometry revealed that activity of T cell decreased with CSBHT concentration. CD4+ T cells were isolated and cultured ,in CSBHT containing medium for 48 hr. CSBHT did not affect survival of sorted CD4+ T cells without any involvement of APC. In order to evaluate the direct effect of CSBHT on helper T cells's proliferative capacity prior to activation, CD4+ T cells are isolated after 24hr of culture in CSBHT containing medium and activated with and without anti-CD3e/anti-CD28 activation for 48hr. A higher level of CD69 was observed in 1 ㎍/㎖ of CSBHT treatment than control using flow cytometry. But low CD69 expression was observed in 5㎍/㎖ of CSBHT treatment. Expression of mRNA for cytokines in CD4+ T cell revealed that IL-2 expression was increased in 1 ㎍/㎖. The expression of IL-2R α, INF- γ were increased with concentration. On the other hand mRNA of IL-4 was decreased in dose dependent manner. Results suggest that CSBHT may be desirable for CD4+ T cell's activity in immune responses. Further more, CSBHT may relatively activate Th1 and inactivate Th2.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.89-110
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• 1998

Yookmijihwangtang has been widely used oriental herb prescriptions, which is healing some discuss that come from insufficiency of innate essence and deficiency of kidney Ki. The meaning of healing discusses tonification of insufficient innate essence and insufficient kidney Ki can be regarded as reinforcement of wholely power of keeping homeostasis, that is correlated with immuno-responsibility which protects subject from outer antigen to keep normal vital condition. This study was aimed to investigate correlative effects of Yookmijihwangtang water abstract on the RBC, WBC, blood CD4+ T helper cell count, blood testosterone, blood cAMP and blood cortisol. 40 Sprague-Dawley male rats were divided into 5 groups(Normal, Control, Sample I, Sample II, Sample III), 6 animals in every group. Normal group was not treated anything, control group was administrated normal saline in the same dosage of Sample I. 3 Sample groups were received some of Yookmijihwangtang water abstract at one time per 24 hours during 5 days in different dosage. Sample I(1/310pack/ml), Sample II(1/62pack/ml), Sample III(1/2.4pack/ml). After finishing treatment, all experimental subjects were killed for blood sample on RBC, WBC, blood CD4+ T helper cell count, spleen CD4+ T helper cell count, axillary lymph node CD4+ T helper cell count. blood cAMP, blood testosterone and blood cortisol. The results were as follows; RBC and WBC were increased in all sample groups. Blood CD4+ T helper cell count(CD4+ T cell count in the blood/whole lymphocyte count in the blood ${\times}100%$) was Normal $46.17{\pm}5.88$, Control $44.50{\pm}4.37$, Sample I $53.00{\pm}2.28$, Sample II $53.83{\pm}3.87$, Sample III $52.17{\pm}2.93$. By the 95% Duncan ANOVA all experimental groups(sample I, Sample II, Sample III) showed slight significant difference from Normal and Control. Blood cAMP(nmol/l) were Normal $1.12{\pm}0.17$, Control $1.16{\pm}0.32$, Sample I $0.46{\pm}0.07$, Sample II $0.44{\pm}0.04$, Sample III $0.54{\pm}0.04$. All experimental groups were singificantly different from both Normal and Control groups(p<0.05). Blood cortisol(nl/ml) were Normal $100.00{\pm}2.00$ Control $90.00{\pm}4.00$, Sample I $440.00{\pm}5.00$, Sample II $520.00{\pm}40.00$, Sample III $470.00{\pm}7.00$. Blood cortisol of all experimental groups were significantly increased(p<0.05). The results suggest that Yookmijihwangtang water abstract could be administrated to patients who have some diseases insufficient essence.