• Title/Summary/Keyword: CD4 cell

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CD8-dependent Tumor Growth Inhibition by Tumor Cells Genetically Modified with 4-1BBL

  • Kim, Hong Sung
    • Biomedical Science Letters
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    • v.27 no.4
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    • pp.329-333
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    • 2021
  • We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.

Pseudo type HIV-1 Particles Carrying CD4

  • Park, Seung-Won;Kim, Tai-Gyu;You, Ji-Chang;Schubert, Manfred;Paik, Soon-Young
    • The Journal of Korean Society of Virology
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    • v.30 no.1
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    • pp.83-99
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    • 2000
  • A defective HIV-1 helper virus DNA, pHyPC, was assembled by deleting the RNA packaging signal, env, nef and the 3'LTR sequences. HIV-1 like virus particles that carry the HIV-1 receptor, CD4 were generated by co expression of pHyPC and plasmid DNAs encoding different chimeric CD4 proteins. The CD4 particles, sharing the CD4 ectodomain, precisely fused to different membrane anchors. CD4(+) particles specifically bound to HIV-1 Env expressing cells, but any signs of infection into these cells were not detected. Binding was only partially blocked by either polyclonal anti-CD4 antibodies or by high concentrations of soluble CD4. Surprisingly, CD4(+) particles also adsorbed to HeLa, CHO, NIH3T3 and COS-7 cells in the absence of HIV-1 Env expression. Adsorption was comparable in strength and speed to the highly specific CD4-Env interaction. CD4(-) particles exhibited only background levels of binding. Cell binding was CD4. dependent, but it was independent of the cell type from which the CD4(+) particles originated. Interestingly, CD4-dependent/Env-independent binding was only found when CD4 was present on virus particles. This suggests that the micro-environment of CD4 on virus particles uniquely expose this new cell binding activity. Its high affinity could explain in part why infection of Env(+) cells by CD4(+) particles was not detected. Further experiments will be required to evaluate whether this strong membrane interaction could represent one step in the multiple-step viral entry process.

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Chimeric Protein of CD8a Extracellular Domain and CD4 Transmembrane and Cytoplasmic Domain Binds More Efficiently to p561ck than CD8a

  • Young Il Choi;Sang Dai Park;Rho Hyun Seong
    • Animal cells and systems
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    • v.3 no.3
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    • pp.331-336
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    • 1999
  • p56$^{Ick}$, a cytoplasmic protein tyrosine kinase of the src family, is non-covalently associated with the cell surface coreceptors CD4 and CD8, which are expressed on thymocytes and mature T cells. The coreceptor protein plays an important role during the differentiation of thymocytes and the activation of T cells. DNA constructs were designed to study the roles of CD4 and CD8 during the differentiation of thymocytes. One is a chimeric cDNA which consists of coding regions for the extracellular domain of CD8a and the transmembrane and cytoplasmic domain of CD4. The other is the same chimeric cDNA but with a point mutation converting Cys to Ala in the Ick-binding site to disrupt the association. We confirmed that the CD8a/CD4 chimeric molecule bound to Ick more efficiently than the wild type CD8a protein. However, the chimeric protein with the Cys$leftrightarro$Ala mutation did not associate with Ick. The results suggest a possibility that the CD8a/CD4 chimeric protein may behave like a CD4 protein in associating with Ick and that it may deliver a signal inside the cell in a similar manner, Analysing effects of the mutant CD8a/CD4 chimeric protein expression in developing thymocytes will elucidate the role of Ick during the determination of CD4/CD8 cell lineages.

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Effects of Atopy Cream-combined with Jawoongo Ointment on the Development of Atopic Dermatitis-like Skin Lesions in NC/Nga Mouse (아토피 피부염 동물 모델에서 아토피 크림과 자운고(紫雲膏)의 병용도포가 피부염에 미치는 영향)

  • Yeo, Eui-Ju;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.23 no.1
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    • pp.37-72
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    • 2009
  • Objectives The purpose of this study is to investigate the suppressive effects of Atopy cream-combined with Jawoongo ointment (A-J), on the development of atopic dermatitis-like skinlesions in NC/Nga mouse. Methods We evaluated clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mouse, analyzed the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue in NC/Nga mouse. Results A-J decreased the clinical skin score, total cell number of WBC, platelet, neutrophils, eosinophils in blood, Serum total IgE & IgG1, IL-5, IL-13. Also, total cell number of ALN and dorsal skin tissue, Absolute cell number of $CD3e^+$&$CD19^+$, $CD4^+$&$CD8^+$, $CD3^+/CCR3^+$, $CCR3^+$, $CD3^+/CD69^+$, $CD3^+/CXCR5^+$ in ALN, PBMCs, Absolute cell number of $CCR3^+$, $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ in dorsalskin tissue, Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue and gene expression of IL-5 mRNA, IL-13 mRNA in ALN decreased significantly. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, histologic infiltration of mast cell, the size of inflammatory lymphocytes cells and plasma cells in ALN and histologic infiltration of CD4+ & CCR3+ in ALN and dorsal skin tissue decreased significantly. However, total cell number of DLN, absolute cell number of $CD3e^+$&$CD19^+$, $CD4^+$&$CD8^+$, $B220^+/CD23^+$, $CD3^+/CD69^+$ increased significantly. Conclusions A-J was the successful treatment of atopic dermatitis in a NC/Nga mouse model.

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Effects of Chungsangboha-tang on Activity of Naive CD4+ T cell (청상보하탕이 Naive CD4+ T cell의 활성에 미치는 영향)

  • Park Young Sik;Bae Hyun Su;Hong Moo Chang;Shin Min Kyu
    • 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.

Isolation of CD4 Genomic Clones and Role of Its 5' Upstream Region in CD4 Expression

  • Youn, Hyun-Joo
    • Korean Journal of Microbiology
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    • v.30 no.6
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    • pp.488-494
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    • 1992
  • Three clones containing mouse CD4 gene were prepared using AKR genomic cosmid library. The role of 6, 500 bp 5' flanking region of the first exon of the AKR CD4 gene in tissue or developmental stage specific expression of CD4 has been studied. The deletion constructs containing various amounts of CD4 5' flanking sequences were prepared, and they were transfected into the cell lines representing different cell types or developmental stages of CD4 expression. Study of the reporter gene expression revealed that at least 1, 700 bp of 5' flanking region did retain promoter activity for CD4 expression. This area did not seem to contain enhancer activity for a full expression of CD4. However, the putative promoter interacted with other tissue specific enhancer sequence and showed the tissue specificity of the enhancer element.

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The Protective Effects of N-Acetyl-L-cysteine on Cadmium-induced Cell Apoptosis in Rat Testis

  • Kim, Ji-Sun;Soh, Jaemog
    • Biomedical Science Letters
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    • v.25 no.4
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    • pp.417-425
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    • 2019
  • Cadmium (Cd) generates reactive oxygen species (ROS), which in turn cause the apoptosis of various cell types including developing germ cells in rodent testis. Ascorbic acids (AA), one of the ROS scavengers, had been reported to protect against Cd-induced apoptosis. N-Acetyl-L-cysteine (NAC), another ROS scavenger, is known to remove ROS and alleviate the Cd-induced apoptosis in various cell types. In this study we tried to elucidate how NAC affected on Cd-induced cell apoptosis in rat testis. Rats were administered with NAC before and after Cd treatment and then testicular cell apoptosis was examined. NAC treatment resulted in the reduction of Cd-induced chromosomal DNA fragmentation in agarose gel electrophoresis. Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed that treatment of NAC reduced the Cd-induced apoptosis of germ cells. The administration of NAC showed that the translocation of apoptosis inducing factor (AIF) from mitochondria to nucleus was prevented, which indicated that the mechanism of Cd-induced testicular apoptosis is mediated through the release of AIF in caspase-independent manner. Taken together, the NAC may remove Cd-induced ROS and protect ROS-induced cell apoptosis in rat testis.

The Effects of Extracts Mixture Drink from Inonotus Obliquus, Phellinus Linteus and Ganoderma Lucidum on Hematopoietic Stem Cells and Lymphocyte Subset of Blood in Human (차가버섯, 상황버섯 및 영지버섯 복합추출물 복용이 인체의 혈중 조혈모세포와 면역세포에 미치는 영향)

  • Bae, Hyung-Suk;Kang, Sung-Keun;Shin, Il-Seob;Woo, Sang-Kyu;Kim, Yun-Joung;Kim, Mi-Ae;Ra, Jeong-Chan
    • Journal of Food Hygiene and Safety
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    • v.24 no.1
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    • pp.78-85
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    • 2009
  • This study was performed to investigate the effect of extract mixture(IPGE) drink from Inonotus Obliquus, Phellinus Linteus and Ganoderma Lucidum on hematopoietic stem cells and lymphocyte subset[lymphocyte, $CD4^+T$ cell, $CD8^+T$ cell, Natural Killer(NK) cells] of blood in 37 participants who were healthy and about $40{\sim}70$ years old. They were divided into two groups; extract mixture drink administration group(n=27) and placebo administration group(n=12). They were given the test drink daily for 4 weeks. Blood was obtained from the subjects every two week in the beginning of administration day to evaluate the $CD34^+$ hematopoietic stem cells and immune cells. As results, $CD34^+$ hematopoietic stem cells were significantly increased after taking IPGE drink for 4 weeks compared to that before taking the drink (p<0.001). There was no significant changes in number of lymphocytes, $CD4^+T$ cells, $CD8^+T$ cells, NK cells and in the ratio of $CD4^+/CD8^+$ cell after taking the test drink. From these results, it was suggested that IPGE have a good health effect by promoting the proliferation of the hematopoietic stem cells.

The Effect of Changiga on Immune Cell & Serum OA-specific IgE in BALF in Rat Asthma Model (창이자(蒼耳子)가 제 I 형 알레르기 천식(喘息)모델 흰쥐의 BALF내(內) 면역세포(免疫細胞) 및 혈청(血淸) IgE에 미치는 영향(影響))

  • Lee Byoung-Hee;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.5 no.2
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    • pp.93-105
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    • 2001
  • BACKGROUND : Changiga is a hetnal medicine which has been used of the traditional therapeutic agent of asthma. So I examine the effect of Changija on immune Cell&serum OA-specific IgE in BALF in rat asthma model. MATERIAL and METHODS : Rats were sensitized with OA; at day 1 sensitized group and Changiga(CIG) groups were systemically immunized by subcutaneous ingection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1ml of 0.9% saline containing $6{\times}109$ B. pertussis bacilli was injected by i.p. 14 days, after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerocol containing 2%(wt/vol) OA, A day after local immunization, BAL fluid was collected from the rats. A day after local immunization, rats were orally administered with Changiga extract 14 days, Lymphocyte, CD4+ T-cell CD8+ T-cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level in the peripheral blood were measured and evaluated. RESULT : Changiga showed a suppressive effect on a rat asthme model. Changiga decreased lymphocyte, CD4+ T-cell, CD4+/CD8+ ratio in BALF, serum OA-specific IgE level as compared with the control group, whereas Changiga decreased CD8+ T-cell in BALF with statistical nonsignificance as compared with the control group. CONCLUSION: This study shows that Changiga have a suppressive effect on rat allergic athma model. Changiga would be useful allergic asthma treatment agent.

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The Effects of Herbal-acupuncture with Aconiti Iateralis Preparata Radix solutionon Collagen-induced arthritis (부자약침(附子藥鍼)이 흰쥐의 Collagen 유발 관절염에 미치는 영향)

  • Kim, Yoon-Hee;Yim, Yun-Kyoung;Lee, Hyun
    • Korean Journal of Acupuncture
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    • v.23 no.2
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    • pp.137-154
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    • 2006
  • Results: 1. In the AlPR-HA group, the incidence of arthritis and arthritis index were significantly decreased. 2. In the AlPR-HA group, the levels of $IL-6,\;IFN-{\gamma},\;TNF-{\alpha},\;IL-1{\beta},\;IgG,\;IgM,\;Anti-collagen\;II$ in serum of the CIA mouse were significantly decreased. 3. In the AlPR-HA group, the levels of $IFN-{\gamma:,\;IFN-{\gamma}\;/IL-4$ in spleen cell culture of the CIA mouse were significantly decreased. 4. In the Hematoxylin and eosin stain, the cartilage destruction and synovial cell proliferation were decreased in the AIPR-HA group. 5. In the Masson's trichrome stain, the collagen fiber expressions were similar with that of the Normal group. 6. In the AlPR-HA group, the expression ratio of $CD3e^+$ to $CD19^+$ cell and $CD4^+$ to $CD8^+$ cell were similarly maintained as Normal group in the CIA mouse lymph nodes. 7. In the AlPR-HA group, $CD3e^+/CD69^+$ cells in the CIA mouse joint and $CD11a^+/CD19^+$ cells and $CD11b^+/Gr-1^+$ cells in the CIA mouse lymph nodes were significantly decreased. 8. In the AIPR-HA group, $CD4^+/CD25^+$ cells were significantly decreased in the CIA mouse spleen cell and were similarly maintained as Normal group in the CIA mouse lymph nodes. Conclusions: These results suggest that AlPR-HA at 51'36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

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