• Title/Summary/Keyword: CD8+ T cells

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CD4+ cytotoxic T cells: an emerging effector arm of anti-tumor immunity

  • Seongmin Jeong;Nawon Jang;Minchae Kim;Il-Kyu Choi
    • BMB Reports
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    • v.56 no.3
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    • pp.140-144
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    • 2023
  • While CD8+ cytotoxic T cells have long been considered the primary effector in controlling tumors, the involvement of CD4+ "helper" T cells in anti-tumor immunity has been underappreciated. The investigations of intra-tumoral T cells, fueled by the recent advances in genomic technologies, have led to a rethinking of the indirect role of CD4+ T cells that have traditionally been described as a "helper". Accumulating evidence from preclinical and clinical studies indicates that CD4+ T cells can acquire intrinsic cytotoxic properties and directly kill various types of tumor cells in a major histocompatibility complex class II (MHC-II)-dependent manner, as opposed to the indirect "helper" function, thus underscoring a potentially critical contribution of CD4+ cytotoxic T cells to immune responses against a wide range of tumor types. Here, we discuss the biological properties of anti-tumor CD4+ T cells with cytotoxic capability and highlight the emerging observations suggesting their more significant role in anti-tumor immunity than previously appreciated.

Development of Portable AIDS Diagnosis Device (휴대용 AIDS 검사기기 개발)

  • Singh, Birendra Kumar;Tae, Gun-Sik;Sung, Yeon-Moon
    • Journal of Appropriate Technology
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    • v.7 no.2
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    • pp.211-215
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    • 2021
  • It is estimated that there are 40 million people with AIDS worldwide, with most cases occurring mainly in developing countries. HIV, the virus that causes AIDS, is infected with CD4+ T cells in the blood and gradually destroys CD4+ T cells for several months to 10 years, thereby lowering the patient's immune function. AIDS patients who have weakened immunity in this way will die from various diseases. The current method for counting the number of CD4+ T cells is usually performed by flow cytometry. The flow cytometry method has the advantage of high accuracy, but it is difficult to use in developing countries because it requires skilled professionals and equipment is expensive. As a result of this study, a device for AIDS screening was developed by capturing leukocytes from a small amount of 5 ㎕ blood through a microfilter and analyzing CD4+ T cells and CD8+ T cells from the captured cells. cheaper and easier to carry and use than current test equipment.

Effector Memory CD8+ and CD4+ T Cell Immunity Associated with Metabolic Syndrome in Obese Children

  • Yang, Da-Hee;Lee, Hyunju;Lee, Naeun;Shin, Min Sun;Kang, Insoo;Kang, Ki-Soo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.24 no.4
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    • pp.377-383
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    • 2021
  • Purpose: We investigated the association of effector memory (EM) CD8+ T cell and CD4+ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8+ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4+ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rαlow CD8+ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7RαlowCX3CR1+ CD8+ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7RαlowCX3CR1+ and IL-7RαhighCX3CR1- CD8+ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4+ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8+ T cells might be related to the morbidity of obesity.

Antitumor Effects of Duck′s Egg Oil on the Cancer Cells (청둥오리 압란유의 항암 효과)

  • 류병호;김민정;양승택
    • Journal of Life Science
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    • v.12 no.1
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    • pp.61-66
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    • 2002
  • This study were constructed to investigate effects of duck's egg oil on antitumor agent or a new natural immunomodulator. To obtained the aboved objectives, Duck's egg oil was purified the large scale from Duck. Duck's egg oil was accelerated the increasing reaction of mouse spleen cells, while inhibited to increase the YAC-cells. However, there is no significance the rate of CD4'/CD8'cell. The normal rate of CD4'-T and CD8'-T cells were accelerated the higher rate than that normal mouse group, and Duck's egg oil feeding mice showed a significant enhancement of expression of IL-2 receptors, an increase of numbers of CD4+ T cells, CD8+ T cells. Otherwise, Duck's egg oil stimulated the production of NO from peritoneal macrophages and the production of TNF-a and also significantly accelerated in the spleen mice. On the other hands, lung localization of B16F10 melanoma cells inhibited by Duck's egg oil. These results found that Duck's egg oil is useful new functional materials as antitumor agent or immunomodulator.

Neural-Cadherin Influences the Homing of Terminally Differentiated Memory CD8 T Cells to the Lymph Nodes and Bone Marrow

  • Kim, Kyong Hoon;Choi, Aryeong;Kim, Sang Hoon;Song, Heonju;Jin, Seohoon;Kim, Kyungim;Jang, Jaebong;Choi, Hanbyeul;Jung, Yong Woo
    • Molecules and Cells
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    • v.44 no.11
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    • pp.795-804
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    • 2021
  • Memory T (TM) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how TM cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, TM cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin+ cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of TM cells. The numbers of CD127hiCD62Lhi TM cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127loKLRG1hi TM cells were adoptively transferred into anti-N-cadherin-treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, without functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127hiCD62Lhi TM cells and homing of CD127loKLRG1hi TM cells to lymphoid organs.

CD30-Mediated Regulation of Cell Adhesion Molecule Expression on Murine T Cells

  • Nam, Sang-Yun
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.8-15
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    • 2003
  • Background: CD30 is a member of TNF receptor family and expressed on lymphocytes and other hematopoietic cells following activation as well as Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma. In this study, CD30-mediated regulation of cell adhesion molecule expression on normal activated mouse T cells was investigated. Methods: Mouse T cells were activated with anti-CD3 antibody for induction of CD30, which was cross-linked by immobilized anti-CD30 antibody. Results: High level of CD30 expression on T cells was observed on day 5, but only little on day 3 even under culture condition resulting in an identical T cell proliferation, indicating that CD30 expression requires a prolonged stimulation up to 5 days. Cross-linking of CD30 alone altered neither proliferation nor apoptosis of normal activated T cells. Instead, CD30 appeared to promote cell adherence to culture substrate, and considerably upregulated ICAM-1 and, to a lesser extent, ICAM-2 expression on activated T cells, whereas CD2 and CD18 (LFA-1) expression was not affected. None of cytokines known as main regulators of ICAM-1 expression on tissue cells (IL 4, $IFN{\gamma}$ and $IFN{\alpha}$) enhanced ICAM-1 expression in the absence of CD30 signals. On the other hand, addition of $NF-{\kappa}B$ inhibitor, PDTC (0.1 mM) completely abrogated the CD30-mediated upregulation of ICAM-1 expression, but not CD2 and ICAM-2 expression. Conclusion: This results support that CD30 upregulates ICAM-1 expression of T cell and such regulation is not mediated by higher cytokine production but $NF-{\kappa}B$ activation. Therefore, CD30 may play important roles in T-T or T-B cell interaction through regulation of ICAM-1, and -2 expression.

Ulmi Cortex Prevents Cisplatin-Induced Apoptosis in Mice (시스플라틴에 의한 세포고사에서 유근피(楡根皮)의 효과)

  • Moon, Mi-Hyun;Jeon, Ji-Young;Lee, Seon-Ah;Shin, Yong-Jeen;Ko, Seok-Jae;Moon, Goo
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.229-241
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    • 2008
  • Objectives : The purpose of this study is to investigate the effect of Ulmi Cortex(UC) on the cisplatin-induced cell death. Materials and Methods : I examined several kinds of cell populations such as $CD4^+$ T cells, $CD8^+$ T cells, macrophages and dendritic cells in spleen. Result : When cisplatin was injected to mice, UC recovered total number of cells in spleen and also the number of T cells, macrophages and dendritic cells. UC also effected the activation of $CD4^+$ and $CD8^+$ T cells such as $CD25^+$, $CD69^+$ cells. To further investigate the effect of UC on the cisplatin-induced cell death, I examined the death of splenocyte and total T cells. UC inhibited cisplatin-induced cell death. Conclusion : Taken together, my results suggest that UC may be a beneficial oriental medicine for side effects during anti-tumor therapy.

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Marked Expansion of CD11c+CD8+ T-Cells in Melanoma-bearing Mice Induced by Anti-4-1BB Monoclonal Antibody

  • Ju, Seong-A;Park, Sang-Min;Lee, Sang-Chul;Kwon, Byoung S.;Kim, Byung-Sam
    • Molecules and Cells
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    • v.24 no.1
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    • pp.132-138
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    • 2007
  • 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of $CD11c^+CD8^+$ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of $IFN-{\gamma}$ in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the $CD11c^+CD8^+$ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, $IFN-{\gamma}$ and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that $CD11c^+CD8^+$ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.

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 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.