• Title/Summary/Keyword: $CD4^+$

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Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells

  • Yoon, Hyunyee;Sung, Ji Hyun;Song, Moon Jung
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.154-165
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    • 2021
  • This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

Resveratrol Suppresses CD4+ T Cell Activation and Differentiation in vitro (Resveratrol의 CD4+ T 세포 활성과 분화 억제 효과)

  • Seo, Dong-Won;Yi, Young-Joo;Lee, Sang-Myeong
    • Korean Journal of Plant Resources
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    • v.27 no.5
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    • pp.567-575
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    • 2014
  • Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

Anti-CD137 mAb Deletes Both Donor $CD4^+$ and $CD8^+$ T Cells in Acute Graft-versus-host Disease

  • Kim, Ju-Yang;Cho, Hong-Rae;Kwon, Byung-Suk
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.428-430
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    • 2011
  • We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective $CD4^+$ T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor $CD8^+$ T cells as well as donor $CD4^+$ T cells in the $C57BL/6{\rightarrow}unirradiated$ $(C57BL/6\;{\times}\;DBA/2)F1$ acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive $CD4^+$ and $CD8^+$ T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.

The Effect of Thernal Annealing and Growth of $CdIn_2S_4$ Single Crystal Thin Film by Hot Wall Epitaxy (Hot Wall Epitaxy(HWE)법에 의해 성장된 $CdIn_2S_4$ 단결정 박막 성장의 광학적 특성)

  • Yun, Seok-Jin;Hong, Kwang-Joon
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2006.11a
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    • pp.129-130
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    • 2006
  • A stoichiometric mixture of evaporating materials for $CdIn_2S_4$ single crystal thin films was prepared from horizontal furnace. To obtain the single crystal thin films, $CdIn_2S_4$ mixed crystal was deposited on thoroughly etched semi-insulating GaAs(100) substrate by hot wall epitaxy(HWE) system. The source and substrate temperatures were $630^{\circ}C$ and $420^{\circ}C$, respectively. After the as-grown $CdIn_2S_4$ single crystal thin films was annealed in Cd-, S-, and In-atmospheres, the origin of point defects of $CdIn_2S_4$ single crystal thin films has been investigated by the photoluminescence(PL) at 10 K. The native defects of $V_{cd}$, $V_s$, $Cd_{int}$, and $S_{int}$, obtained by PL measurements were classified as a donors or acceptors type. And we concluded that the heat-treatment m the S-atmosphere converted $CdIn_2S_4$ single crystal thin films to an optical p-type. Also. we confirmed that In in $CdIn_2S_4$/GaAs did not form the native defects because In in $CdIn_2S_4$ single crystal thin films existed in the form of stable bonds.

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Crystal Growth of Cd4GeS6 and Cd4GeS6:Co2+Single Crystals ($Cd_{4}GeS_{6}$$Cd_{4}GeS_{6}:Co^{2+}$ 단결정의 성장)

  • Kim, D.T.;Kim, H.G.;Kim, N.O.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2004.11b
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    • pp.1-6
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    • 2004
  • In this paper author describe the undoped and $Co^{2+}$ (0.5mole%)doped $Cd_4GeS_6$ single crystals were grown by the chemical transporting reaction(CTR) method using high purity(6N) Cd, $GeS_2$, S elements. It was found from the analysis of X-ray diffraction that the undoped and $Co^{2+}$(0.5mole%) doped $Cd_{4}GeS_{6}$ compounds have a monoclinic structure in space grop Cc. The optical energy band gap was direct band gap and temperature dependence of optical energy gap was fitted well to Varshni equation. Impurity optical absorption peaks due to the doped cobalt in the $Cd_4GeS_6:Co^{2+}$ single crystal were observed at 3593cm-1, 5048cm-1, 5901cm-1, 7322cm-1, 12834cm-1, 13250cm-1, 14250cm-1,and 14975cm-1 at 11.3K.

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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.

Deletion Timing of Cic Alleles during Hematopoiesis Determines the Degree of Peripheral CD4+ T Cell Activation and Proliferation

  • Guk-Yeol Park;Gil-Woo Lee;Soeun Kim;Hyebeen Hong;Jong Seok Park;Jae-Ho Cho;Yoontae Lee
    • IMMUNE NETWORK
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    • v.20 no.5
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    • pp.43.1-43.11
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    • 2020
  • Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44hiCD62Llo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4+CD8+ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4+ T cell activation and proliferation between whole immune cell-specific Cic-null (Cicf/f;Vav1-Cre) and T cell-specific Cic-null (Cicf/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4+ T cells were more apparent in Cicf/f;Vav1-Cre mice than in Cicf/f;Cd4-Cre mice. Cicf/f;Vav1-Cre CD4+ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cicf/f;Cd4-Cre CD4+ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cicf/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4+ T cells than did mixed wild-type and Cicf/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4+ T cells with enhanced T cell activation and proliferative capability.

THE LEVELS OF INTERLEUKIN-2, INTERFERON-γ, INTERLEUKIN-4 AND TLYMPHOCYTE SUBPOPULATIONS IN RAT PULPAL INFLAMMATION INDUCED EXPERIMENTALLY BY SPECIFIC BACTERIA (특정 세균으로 유도된 백서의 치수염에서 T 세포 아군집의 분포와 interleukin-2, interferon-γ, interleukin-4의 수준에 관한 연구)

  • Kim, Seon-Ah;Lim, Sung-Sam
    • Restorative Dentistry and Endodontics
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    • v.27 no.1
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    • pp.1-11
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    • 2002
  • Immune responses associated with bacterial infection involve various inflammatory cells. Clinical symptoms and pathologic features are particularly influenced by the predominant cells Among inflammatory cells, T cells have the heterogenity. T cells may develop into the mature cells expressing the cell surface markers with different functions and T helper cells are categorized into Th1 and Th2 cells based on their different patterns of cytokine production. The objective of this study was to investigate the change of expression of surface markers on T cells and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. We experimentally induced pulpal inflammation in rat incisors by drilling without coolant and innoculated with Streptococcus mutans (S.M. group), Porphyromonas endodontalis (P.E. group), or only sterile cotton (control group). After 1, 2, and 5 days, mandibular incisors were extracted and the pulp tissues were extirpated The expressions of IL-2 recepters (CD25) and ICAM-1 (CD54) on CD4+ and CD8+ cells in the pulps were determined using a flow cytometer, and the concentration of IL-2, IFN-$\gamma$ and IL-4 was measured by enzyme-linked immunosorbent assay. The results were as follows: 1 In the S.M. group, CD4+ cells were more increased at 2nd day than 1st day and in the P.E. group, CD8+ cells were more increased at 2nd day than 1st day. 2. The percentages of CD4+, CD4+25+ and CD4+54+ cells were decreased in the pulp tissues at 5th day after irritation in all groups. 3. The ratios of CD4+/CD8+, CD4+/CD4+25+ and CD4+/CD4+54+ in the pulps at 2nd day after irritation by P. endodontalis were significantly lower than the other groups. 4. The higher concentrations of IFN-$\gamma$ than IL-4 in the pulps at 2nd day after irritation by P. endodontalis showed that T helper 1 reaction were predominant in the early stage of the pulpal inflammation induced by P. endodontalis. 5. The higher concentrations of IL-4 than IFN-$\gamma$ in the pulps at 1st day and 5th day after irritation by S. mutans were measured but the differences were not significant.

CD7-Specific Single Chain Antibody Mediated Delivery of siRNA to T Cells Inhibits HIV Replication in a Humanized Mouse Model

  • Ban, Hong-Seok;Kumar, Priti;Kim, Na-Hyun;Choi, Chang-Son;Shankar, Premlata;Lee, Sang-Kyung
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2008.05a
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    • pp.62-64
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    • 2008
  • A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

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Effect of Phosphate Fertilizer and Manure in Reducing Cadmium Phytoavailability in Radish-grown Soil (중금속 오염 농경지에서 축분퇴비와 인산비료의 혼용시용에 의한 카드뮴 식물이용성 저감효과)

  • Hong, Chang-Oh;Kim, Sang-Yoon;Kim, Pil-Joo
    • Korean Journal of Environmental Agriculture
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    • v.30 no.3
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    • pp.261-267
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    • 2011
  • ACKGROUND: Cadmium (Cd) has long been recognized as one of most toxic elements. Application of organic amendments and phosphate fertilizers can decrease the bioavailability of heavy metals in contaminated soil. METHODS AND RESULTS: This study was conducted to evaluate effect of combined application of phosphate fertilizer and manure in reducing cadmium phytoavailability in heavy metal contaminated soil. Phosphate fertilizers [Fused and super phosphate (FSP) and $K_2HPO_4$ (DPP)] and manure (M) were applied as single application (FSP, DPP, and M) to combined application (FSP+M and DPP+M) before radish seeding. $K_2HPO_4$ decreased $NH_4OAc$ extractable Cd and plant Cd concentration, mainly due to increases in soil pH and negative charge. However, FSP increased $NH_4OAc$ extractable Cd and plant Cd concentration. Manure significantly increased soil pH and negative charge. Combined application of phosphate fertilizer and manure were much more effective in reducing Cd phytoavailability than a simple application of each component. Calculated solubility diagram indicated that Cd concentrations in the solution of soils amended with phosphate fertilizers and manure were undersaturated with respect to all potential Cd minerals [$Cd_3(PO_4)_2$, $CdCO_3$, $Cd(OH)_2$, and $CdHPO_4$]. Plant Cd concentration and $NH_4OAc$ extractable Cd were negatively related to soil pH and negative charge. CONCLUSION: Alleviation of Cd phytoavailability with phosphate fertilizer and manure can be attributed primarily to Cd immobilization due to the increase in soil pH and negative charge rather than Cd and phosphate precipitation. Therefore, combined application of alkaline phosphate materials and manure is effective for reducing Cd phytoavailability.