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Enhancing T Cell Immune Responses by B Cell-based Therapeutic Vaccine Against Chronic Virus Infection

  • Kim, Min Ki;Lee, Ara;Hwang, Yu Kyeong;Kang, Chang-Yuil;Ha, Sang-Jun
    • 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.

The Effects of Gamichunggumgangwha-tang (Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (Jiaweiliuweidihuang-tang) on Immune Cell & Serum OA-specific IgE in BALF in a Rat Asthma Model (가미청금항화탕 및 가미육미지황탕이 Allergy 천식 모델 흰쥐의 BALF내 면역세포 및 혈청 IgE에 미치는 영향)

  • 조영민;정희재;정승기;이형구
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.1-10
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    • 2003
  • Background : Asthma is a chronic inflammatory disorder under immunological influence. Gamichunggumgangwha-tang (CG, Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (YM, Jiaweiliuweidihuang-tang) are herbal tonics for asthma from traditional herbal medicine. Objective : To evaluate the effect of CG and YM on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in a rat asthma model. Materials and Methods : Rats were sensitized with OA; at day I sensitized group and CG and YM groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by Lp. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BALF was collected from the rats. Rats were orally administered with each of CG and YM extract for 14 days since the day after local immunization. Lymphocyte, CD4+ T cell and CD8+ T cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level, CD4+ T cell and CD8+ T cell percentages in the peripheral blood were measured and evaluated. Results : CG and YM showed an alleviating effect on asthmatic responses of rats. CG decreased total cell, lymphocyte, CD4+ T cells in BALF, and serum OA-specific IgE level as compared with the control group. YM decreased lymphocytes as compared with the control group. CD4+/CD8+ ratio in BALF from the CG and YM groups and serum OA-specific IgE level from the YM group didn't show any significant variation from the control group. Conclusion : CG alleviated asthmatic hyperreactivity of the immune system through CD4+ T cells and serum IgE. Further the study of this immune system modulating mechanism is expected.

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Korean Red Ginseng modulates immune function by upregulating CD4+CD8+ T cells and NK cell activities on porcine

  • Md Jahangir Alam;Mohammad Amjad Hossain;Kiran D. Bhilare;Chang-Won Kang;Jong-Hoon Kim
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.155-158
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    • 2023
  • In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4+ CD8+T cell, CD3-CD172-CD8+ NK cell and CD172+ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immuneenhancing effects by increasing the roles of T cells and NK cell in porcine.

T-Cell Dysfunction and Inhibitory Receptors in Hepatitis C Virus Infection

  • Lee, Jino;Suh, William I.;Shin, Eui-Cheol
    • IMMUNE NETWORK
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    • v.10 no.4
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    • pp.120-125
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    • 2010
  • Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.

Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines

  • Sang-Hyun Kim;Erica Espano;Bill Thaddeus Padasas;Ju-Ho Son;Jihee Oh;Richard J. Webby;Young-Ran Lee;Chan-Su Park;Jeong-Ki Kim
    • IMMUNE NETWORK
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    • v.24 no.3
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    • pp.19.1-19.15
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    • 2024
  • The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

A Nonvolatile Refresh Scheme Adopted 1T-FeRAM for Alternative 1T-DRAM

  • Kang, Hee-Bok;Choi, Bok-Gil;Sung, Man-Young
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.8 no.1
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    • pp.98-103
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    • 2008
  • 1T1C DRAM has been facing technological and physical constraints that make more difficult their further scaling. Thus there are much industrial interests for alternative technologies that exploit new devices and concepts to go beyond the 1T1C DRAM technology, to allow better scaling, and to enlarge the memory performance. The technologies of DRAM cell are changing from 1T1C cell type to capacitor-less 1T-gain cell type for more scalable cell size. But floating body cell (FBC) of 1T-gain DRAM has weak retention properties than 1T1C DRAM. FET-type 1T-FeRAM is not adequate for long term nonvolatile applications, but could be a good alternative for the short term retention applications of DRAM. The proposed nonvolatile refresh scheme is based on utilizing the short nonvolatile retention properties of 1T-FeRAM in both after power-off and power-on operation condition.

Immunocytochemical Study on the Change of the Activated T Cells in Peripheral Blood of the Pulmonary Tuberculosis Patients (폐결핵환자의 말초혈액에서 Activated T Cell의 변화)

  • Ryu, Gyeong-Ryeol;Park, Une-Sook;Park, Chong-Hwa;Jeoung, Pan-Joon;Hwang, Young-Sil;Lee, Yang-Jae;Chang, Ga-Yong
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.823-830
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    • 1995
  • Background: It has been found that Helper T cells in the peripheral blood are decreased in the cell mediated immunity in the pulmonary tuberculosis. But it has not been confirmed yet that only decrease in number of cells which has phenotype in the peripheral blood is defined to decrease in cell mediated immunity. The immunocytochemical study was performed to observe the change of the percentage of T-lymphocytes with their subsets and activated T cells in the peripheral blood of pulmonary tuberculosis and to know how many T cells would be activated, relative to resting cells in the peripheral blood. Methods: The peripheral blood obtained from twenty two patients and ten healthy controls were smeared on the gelatin coated slide glass prepared for of mononuclear cells. The double bridge technique of alkaline phosphatase-antialkaline phosphatase(APAAP) method was used. As the primary antibodies, $T_1$(anti-human T cell), $T_4$(anti-human helper/inducer T cells) and $T_8$(anti-human supressor/cytotoxic T cell) antibodies and interleukin-2 receptor (for early activated T cell), very late activation antigen (for activated cytotoxic T cell), T cell lineage specific activation antigen monoclonal actibodies were used. Results: 1) There were significantly decrease in the absolute number of $T_4$(+) cells but significantly increase of $T_8$(+) cells in the peripheral blood of pulmonary tuberculosis (p<0.05). 2) The percentage of $T_4$(+) cells showed significantly decrease in pulmonary tuberculosis but $T_8$(+)cells significantly increase(p<0.05). $T_4(+)/T_8(+)$ ratio showed significantly decrease in the peripheral blood of the pulmonary tuberculosis(p<0.05). 3) There were significantly increase in the absolute number of variable stages of activated T cells in the peripheral blood of the pulmonary tuberculosis(p<0.05). 4) The percentage of IL-2R, VLA-1, TLiSA were 6.45+1.56%, $7.64+1.34^*$, 10.45+1.16% in order which showed significantly increase in the peripheral blood of the pulmonary tuberculosis(p<0.05). Conclusion: We speculate that only a few percentage of T lymphocyte is activated in cell mediated immunity in pulmonary tuberculosis.

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Resveratrol regulates naïve CD 8+ T-cell proliferation by upregulating IFN-γ-induced tryptophanyl-tRNA synthetase expression

  • Noh, Kyung Tae;Cho, Joon;Chun, Sung Hak;Jang, Jong-Hwa;Cha, Gil Sun;Jung, In Duk;Jang, Dong Deuk;Park, Yeong-Min
    • BMB Reports
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    • v.48 no.5
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    • pp.283-288
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    • 2015
  • We found that resveratrol enhances interferon (IFN)-γ-induced tryptophanyl-tRNA-synthetase (TTS) expression in bone marrow-derived dendritic cells (BMDCs). Resveratrol-induced TTS expression is associated with glycogen synthase kinase-3β (GSK-3β) activity. In addition, we found that resveratrol regulates naive CD8+ T-cell polarization by modulating GSK-3β activity in IFN-γ-stimulated BMDCs, and that resveratol induces upregulation of TTS in CD8+ T-cells in the in vivo tumor environment. Taken together, resveratrol upregulates IFN-γ-induced TTS expression in a GSK-3β-dependent manner, and this TTS modulation is crucial for DC-mediated T-cell modulation. [BMB Reports 2015; 48(5): 283-288]

CD8+ T Cell-mediated Immunity Induced by Heterologous Prime-boost Vaccination Based on DNA Vaccine and Recombinant Vaccinia Virus Expressing Epitope (Epitope발현 DNA Vaccine과 Recombinant Vaccinia Virus를 이용한 Heterologous Prime-boost Vaccination에 의하여 유도되는 CD8+ T 세포 매개성 면역)

  • Park, Seong-Ok;Yoon, Hyun-A;Aleyas, Abi George;Lee, John-Hwa;Chae, Joon-Seok;Eo, Seong-Kug
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.89-98
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    • 2005
  • Background: DNA vaccination represents an anticipated approach for the control of numerous infectious diseases. Used alone, however, DNA vaccine is weak immunogen inferior to viral vectors. In recent, heterologous prime-boost vaccination leads DNA vaccines to practical reality. Methods: We assessed prime-boost immunization strategies with a DNA vaccine (minigene, $gB_{498-505}$ DNA) and recombinant vaccinia virus $(vvgB_{498-505})$ expressing epitope $gB_{498-505}$ (SSIEF ARL) of CD8+ T cells specific for glycoprotein B (gB) of herpes simplex virus (HSV). Animals were immunized primarily with $gB_{498-505}$ epitope-expressing DNA vaccine/recombinant vaccinia virus and boosted with alternative vaccine type expressing entire Ag. Results: In prime-boost protocols using vvgBw (recombinant vaccinia virus expressing entire Ag) and $vvgB_{498-505}$, CD8+ T cell-mediated immunity was induced maximally at both acute and memory stages if primed with vvgBw and boosted with $vvgB_{498-505}$ as evaluated by CTL activity, intracellular IFN-staining, and MHC class I tetramer staining. Similarly $gB_{498-505}$ DNA prime-gBw DNA (DNA vaccine expressing entire Ag) boost immunization elicited the strongest CD8+ T cell responses in protocols based on DNA vaccine. However, the level of CD8+ T cell-mediated immunity induced with prime-boost vaccination using DNA vaccine expressing epitope or entire Ag was inferior to those based on vvgBw and $vvgB_{498-505}$. Of particular interest CD8+ T cell-mediated immunity was optimally induced when $vvgB_{498-505}$ was used to prime and gB DNA was used as alternative boost. Especially CD7+ T cell responses induced by such protocol was longer lasted than other protocols. Conclusion: These facts direct to search for the effective strategy to induce optimal CD8+ T cell-mediated immunity against cancer and viral infection.

The Effect of Herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix, and Astragali Radix on Immune Responses in Rats (보중익기탕(補中益氣湯), 인삼(人蔘) 및 황(黃)기 약침(藥鍼)이 MTX로 약침(誘發)된 백서(白鼠)의 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Kim, Jung-Hun;Park, Hi-Joon;Lee, Hyang-Sook;Lee, Hye-Jung
    • Journal of Pharmacopuncture
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    • v.3 no.2
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    • pp.79-97
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    • 2000
  • Objectives : To investigate the effects of herb-acupunctures of Qi tonification herbs or formula on the rat immune depression induced by an anticancer drug, methotrexate (MTX) Methods: Animals were divided into 5 groups; Normal control group was not given any treatment. Immune depression was induced by oral administration of 1mg/kg MTX b.i.d for 4 days in Control, Sample I, II, and III groups. We treated on CV 4 (Guanyuan) with saline, Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix herb-acupunctures in Control, Sample I, II, and Ill groups, respectively. In both blood and spleen, the assessment of CD4+ T-cell count, CD8+ T-cell count, CD4/CD8 T-cell ratio was performed. Results: Here we show that 3 herb- acupuncture groups have an influence, to some extent, on CD4+ and CD8+ T-cell counts and CD4/CD8 T-cell ratio in both blood and spleen. Astragali Radix herb-acupuncture, in particular, was found to have significantly increased CD4+ T-cell count in blood and CD4/CD8 T-cell ratio in blood and spleen. Conclusions: The results of this study suggest that herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix may have an influence over rat immune depression induced by MTX.