• Title/Summary/Keyword: T-cell response

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Segmented Filamentous Bacteria Induce Divergent Populations of Antigen-Specific CD4 T Cells in the Small Intestine

  • Yi, Jaeu;Jung, Jisun;Han, Daehee;Surh, Charles D.;Lee, You Jeong
    • Molecules and Cells
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    • v.42 no.3
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    • pp.228-236
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    • 2019
  • CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

Construction of Glomerular Epithelial Cells Expressing Both Immune Tolerance and GFP Genes and Application to Cell Therapy by Cell Transplantation

  • Ohga, Masahiro;Ogura, Mariko;Matsumura, Mastoshi;Wang, Pi-Chao
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.7 no.5
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    • pp.303-310
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    • 2002
  • Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the tissue repair. However, when cells are transplanted from in vitro to in vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocy-tosis [1]. Attempting to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified from the same amount of cells to achieve the same effect.

The Effect of Honey Bee Venom Aqua-Acupuncture by its Production from Different Regions on Decreased Immune Response (산지별(産地別) 봉독액약침자극(峰毒液藥鍼刺戟)이 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Lee, Kyung-Hee;Kim, Chang-Hwan;Kang, Sung-Keel;Koh, Hyung-Kyun
    • Journal of Acupuncture Research
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    • v.17 no.4
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    • pp.28-40
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    • 2000
  • Objectives : This study was purposed to investigate the effect of honey bee venom aqua-acupuncture on decreased immune response by its production from Korea, North America and China. Methods : ICR-mouse was exposed with four minute sublethal 60Co- $\gamma$ -ray irradiation onto the body and got a series of each country's 0.1 ml honey bee venom aqua-acupuncture to Choksamni(ST36) every other day for three times. Thereafter the numbers of WBC, delayed type hypersensitivity, hemagglutinin titers, hemolysin titers, quantitation of T-cell and B-cell, lymphocyte transformation, natural killer cell activity, interleukin-2 productivity and interferon productivity were measured. Results : The numbers of WBC, delayed type hypersensitivity, hemagglutinin titers, hemolysin titers, quantitation of T-cell and B-cell and lymphocyte transformation were increased respectively with statistical significance in Korean, North American and Chinese honey bee venom aqua-acupuncture groups as compared with the control group. The natural killer cell activity was increased with statistical significance in Korean honey bee venom aqua-acupuncture group, and Interleukin-2 productivity and interferon productivity were not shown any statistical significance in all experimental groups as compared with the control group. Conclusions : According to the results, honey bee venom aqua-acupuncture has significant effect on decreased immune response, and Korean bee venom can be substituted for North American and Chinese one.

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Effects of Gamgung-tang on Lymphocyte Activities in Immunodeficiency Mice (감궁탕이 면역기능 저하 마우스의 임파구활성에 미치는 영향)

  • Shon Yun Hee;Kim Ho Chang;Moon Ji Sun;Baek Tae Seon;Kim Cheorl Ho;Jeon Byung Hun;Nam Kyung Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.4
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    • pp.995-1000
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    • 2004
  • This study was purposed to investigate the effect of Gamgung-tang(GGT) on immune responses induced by glucocorticoid in mice. GGT solution was treated by intraperitoneal injection for 7 days after glucocorticoid treatment(80㎎/㎏). And then B and T cell proliferation and cytolytic activity of natural killer(NK) cells were measured. There was 25% inhibition in B cell proliferation with treatment of glucocorticoid. However, B cell proliferation was not influenced by GGT treatment. T cell proliferation was also inhibited by 18.4% with treatment of glucocorticoid. On the other hand, T cell proliferation was increased dose-dependent manner in GGT treated group. Furthermore in purified T cell, the proliferation was furtherly increased than non-purified T cell. At concentration of 18㎎/mouse GGT, purified T cell proliferation was increase to above level of normal group. The cytotoxic activity of NK cell was decreased by 35.3% with treatment of glucocorticoid. In GGT treated group, the cytotoxic activity of NK cell was increased to the normal level. In purified NK cell, the cytolytic activity of NK cell was further increased than non-purifed NK cell. These results suggest that GGT may proliferate T cell that is suppressed by glucocorticoid, and activate NK cell activity.

The Transmembrane Adaptor Protein LIME Is Essential for Chemokine-Mediated Migration of Effector T Cells to Inflammatiory Sites

  • Park, Inyoung;Son, Myongsun;Ahn, Eunseon;Kim, Young-Woong;Kong, Young-Yun;Yun, Yungdae
    • Molecules and Cells
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    • v.43 no.11
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    • pp.921-934
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    • 2020
  • Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

Tumor-derived CD4+CD25+ Tregs Inhibit the Maturation and Antigen-Presenting Function of Dendritic Cells

  • Du, Yong;Chen, Xin;Lin, Xiu-Qing;Wu, Wei;Huang, Zhi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2665-2669
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    • 2015
  • CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and $TNF-{\alpha}$ secretion by DCs.

F-18 FDG PET/Cl Findings of Subcutaneous Panniculitis - like T- Cell lymphoma: A Case Report (피하 지방층염양 T-세포 림프종의 F-18 FDG PET/CT 소견)

  • Kong, Eun-Jung;Cho, Ihn-Ho;Chun, Kyung-Ah;Bae, Yeung-Kyung;Choi, Joon-Hyuk;Hyun, Myung-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.3
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    • pp.240-244
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    • 2009
  • F-18 FDG PET is a metabolic imaging modality that is efficacious in staging and assessment of treatment response for variety of lymphomas. We report usefulness of F-18 FOG PET/Cl in evaluating severity of the disease and response to therapy in a patient with subcutaneous panniculitis- like T-cell lymphoma (SPTCL). Here we describe a case of SPTCL in 24-year-old man who had wide spread firm and tender nodular lesions with increased F-18 FOG uptake. After chemotherapy follow up F-18 FDG PET/CT image shows disseminated malignancy and then the patient died with hemophagocytic syndrome. This report suggests that F-18 FDG PET/CT may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected outcome of SPTCL.

Effect of Pedunculagin on IL-1$\beta$ mRNA Expression in Langerhans cells (랑게르한스세포에서 IL-1$\beta$ mRNA 발현에 대한 Pedunculagin의 효과)

  • 주성수;권희승;강희철;이도익
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.472-476
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    • 2002
  • Contact hypersensitivity (CHS) serves as a good model of cell-mediated reaction. Epidermal langerhans cell (LC) are thought to playa crucial role in the regulation of immune reaction of the skin, which elicit the CHS response by presenting Antigen to trafficking Ag-specific T cells within the skin. However, contact hypersensitivity is regarded as a negative side of immunities, caused by increased damaging immune response. Therefore, the study of effector molecule causing immune suppression is thought to be meaningful in the skin immune response. For this aim, this study investigated the influence of pedunculagin on cytokine, IL-$\beta$ expression from langerhans cell (LC). In vitro and in vivo, pedunculagin up-regulated the expression of IL-1$\beta$ mRNA. After PMA stimulation in vitro and DNFB sensitization in vivo, the expression of IL-1$\beta$ mRNA was down-regulated. This results suggested that pedunculagin could be immuno-modulator in skin immune system by modulating IL-1$\beta$ expression.

Electro-optical Properties of Polymer-Stabilized Nematic Pi Cells

  • Huang, Chi-Yen;Fung, Ri-Xin;Lin, Ying-Ging
    • 한국정보디스플레이학회:학술대회논문집
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    • 2007.08a
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    • pp.954-957
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    • 2007
  • We analyzed conditions for fabricating zero-bias polymer-stabilized liquid crystal (PSLC) pi cells. A high curing voltage and a very low curing intensity are effective in fabricating the cell with a high bright state, a low dark state and therefore a steep T-V curve. However, the response time of the cell is slow. Finally, a dual-frequency PSLC pi cell with fast response time is developed. The obtained result reveals that the dual-frequency PSLC pi cell has a fast response of under 1ms.

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Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.