• Title/Summary/Keyword: cytotoxic t lymphocyte

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GLOBAL STABILITY OF VIRUS DYNAMICS MODEL WITH IMMUNE RESPONSE, CELLULAR INFECTION AND HOLLING TYPE-II

  • ELAIW, A.M.;GHALEB, SH.A.
    • Journal of the Korean Society for Industrial and Applied Mathematics
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    • v.23 no.1
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    • pp.39-63
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    • 2019
  • In this paper, we study the effect of Cytotoxic T Lymphocyte (CTL) and antibody immune responses on the virus dynamics with both virus-to-cell and cell-to-cell transmissions. The infection rate is given by Holling type-II. We first show that the model is biologically acceptable by showing that the solutions of the model are nonnegative and bounded. We find the equilibria of the model and investigate their global stability analysis. We derive five threshold parameters which fully determine the existence and stability of the five equilibria of the model. The global stability of all equilibria of the model is proven using Lyapunov method and applying LaSalle's invariance principle. To support our theoretical results we have performed some numerical simulations for the model. The results show the CTL and antibody immune response can control the disease progression.

Dendritic Cells-based Vaccine and Immune Monitoring for Hepatocellular Carcinoma

  • Lee, Dae-Heui
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.1
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    • pp.11-14
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    • 2010
  • Human tumors, including those of the hepatobiliary system, express a number of specific antigens that can be recognized by T cells, and may provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. The ability to culture sufficient numbers of DCs from human bone marrow or blood progenitors has attracted a great deal of interest in their potential utilization in human tumor vaccination. $CD34^+$ peripheral blood stem cells (PBSCs) were obtained from a patient with a hepatocellular carcinoma. The PBSCs were cultured in the X-VIVO 20 medium supplemented with the Flt-3 Ligand (FL), GM-CSF, IL-4 and TNF-$\alpha$ for 12 days. The morphology and functions of the cells were examined. The generated cells had the typical morphology of DCs. When the DCs were reinjected into the same patient, an augmentation of the cytotoxic T lymphocyte (CTL) activity was observed. Concomitantly, an increase in the natural killer (NK) cell activity was also detected in the patient. These results suggest that DCs-based cancer immunotherapy may become an important treatment option for cancer patients in the future.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

  • Hye Won Lee;Yun Shin Chung;Tae Jin Kim
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.5.1-5.15
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    • 2020
  • The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

Immunohistochemical Study on the Suppression of Cell mediated immunity in Lymph node of mouse by Cyclosporin A -Based on the change of T lymphocytes, Il-2 receptors, and NK cells- (Cyclosporin A로 유도된 생쥐 림프절의 세포성 면역억제에 관한 면역조직화학적 연구 -T 림프구, IL-2 수용기 및 NK세포의 변화를 중심으로-)

  • Kim, Jin-Taek;Park, In-Sick;Ahn, Sang-Hyun;Choi, Nan-Hee;Kim, Dong-Hoan
    • The Journal of Dong Guk Oriental Medicine
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    • v.6 no.2
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    • pp.99-107
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    • 1998
  • Cyclosporin A(CsA) is a selective immunosuppressive agent that has been credited with improved survival of solid organ allografts. Lymph node of BALB/C mouse administered CsA immunohistochemically observed to understand immunosuppressive effects of CsA on T lymphocytes, IL-2 receptors, and natural killer NK cells in lymph node. CsA orally administered daily for 10days at the dose 45mg/kg/day/. The lymph node were obtained at day 3, 7, and 14 after CsA administration and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25), and NK-1.1(CD56). There were little changes of reactive degree and number of helper T lymphocytes, cytotoxic T lymphocytes, IL-2 receptors, and NK cells at day 3 after CsA administration, but they began to decrease at day 7. These decrease were greatest at day 14. The helper T lymphocytes. cytotoxic T lymphocytes, IL-2 receptors, and NK cells distributed in paracortex and medullary sinus. These results indicated that the secretion of IL-2 began to decrease at day 7 after CsA administration and subsequently to suppress T lymphocytes and NK cell as components of cell-mediated immunity.

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The effects of properties and interactions of surface molecules in antigen presenting cells on T cell activation (인공 항원제시세포의 표면 분자의 특성 및 상호작용이 T 세포 활성화에 미치는 영향)

  • Min, Youngsil;Kang, Yoon Joong
    • Journal of Convergence for Information Technology
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    • v.10 no.6
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    • pp.164-176
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    • 2020
  • Efficient production of antigen specific cytotoxic T cells is critical for appropriate adoptive immune response. In vitro culture and expansion of human T lymphocyte clones are very sophisticated and subtle procedure in immune cell therapy and hard to control. Therefore, many groups devoted their efforts to manipulate artificial antigen presenting cells (aAPCs) that can induce T cell activation and clonal expansion. To mimicking of natural antigen-presenting cells, aAPCs encompass basic signal molecules required for T cell activation: MHC:antigen complexes, co-stimulatory molecules and soluble immune modulating molecules. Orchestrated organization of these molecules is important for efficient T cell activation. Here, we discuss how those molecules have been incorporated in several aAPC models, but also how physical properties od aAPC are important for interaction with T cells.

Effects of Proline and Gelatin on hCTLA4Ig Production in Transgenic Rice Suspension Cells (형질전환 벼 현탁세포를 이용한 hCTLA4Ig 생산에서 proline과 gelatin이 미치는 영향)

  • Song, Mi-Na;Cheon, Su-Hwan;Kwon, Jun-Young;Choi, Sung-Hun;Kim, Dong-Il
    • KSBB Journal
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    • v.24 no.3
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    • pp.246-252
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    • 2009
  • Rice cells were transformed to express human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) using RAmy3D promoter. hCTLA4Ig was produced and secreted into culture media inducibly when sugar was depleted. The obstacles of this system are the cell death and release of proteases by sugar starvation. These problems resulted in the losses of stability and productivity of hCTLA4Ig. Therefore, the effects of proline as an inhibitor of cell death were investigated. When 4 mM proline was added in sugar-free media, the cell death and release of proteases were reduced. As a consequence, the production of hCTLA4Ig was enhanced. In addition, the effects of protein stabilizers such as gelling agents were studied. It was found that the application of 0.01 g/L gelatin led to an increase in hCTLA4Ig production. This increase might be originated from the stabilization of hCTLA4Ig. In conclusion, the production of hCTLA4Ig could be enhanced by the additions of proline and gelatin in transgenic rice cell cultures.

T-cell Mediated Immunity in Pulmonary and Extrapulmonary Tuberculosis (폐 및 폐외결핵환자에서의 T 림프구 매개성 면역기능의 변화에 관한 연구)

  • Choi, Dong-Chull;Shim, Tae-Sun;Cho, Sang-Heon;Jung, Ki-Ho;Hyun, In-Gyu;Yoo, Chul-Gyu;Kim, Young-Whan;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.1
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    • pp.62-72
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    • 1992
  • Background: T-cell mediated cellular immunity has been suggested as an important mechanism in mycobacterial infection and imbalance between helper/inducer and suppressor/cytotoxic T-cell has been suggested as an important immunological abnormality in the pathogenesis of tuberculosis in human. Method: To determine whether there is any difference in T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis, total numbers of WBC&lymphocytes were counted and helper/inducer and suppressor/cytotoxic cells were calculated by flow cytometry. Blastogenesis after stimulation with Concanavalin-A, Phytohemagglutinin and PPD were measured by $^3H$-thymidine uptake. PPD skin test was performed as an in vivo test. Results: 1)There was no significant difference in the size of PPD skin test between pulmonary and extrapulmonary tuberculosis groups. 2)Number of total lymphocytes significantly decreased in tuberculosis patients compared with healthy control group. But there was no significant difference between pulmonary and extrapulmonary tuberculosis groups. 3) Number of HLA-DR and Interleukin-2 receptor (+) cells were significantly increased in tuberculosis patients. But there was no significant difference between pulmonary and extra pulmonary tuberculosis groups. 4) There was no significant difference in the numbers of WBC, $T_3$, $T_4$ and $T_8$ lymphocytes and $T_4/T_8$ ratio between tuberculosis patients and healthy controls. 5) There was no significant difference in the blastogenesis after stimulation with specific and non-specific blastogens between tuberculosis patients and healthy controls. 6) The percentage and absolute number of $T_4$ lymphocyte were significantly correlated with the size of PPD skin test. (r=0.689 and 0.598). Conclusion: From these results, it is concluded that there was no difference in T-cell mediated immunity between pulmonary and extra pulmonary tuberculosis group. But, because it is suspected that there might be some difference in the role of T-cell mediated immunity in the pathogenesis of pulmonary and extra pulmonary tuberculosis or even among the extrapulmonary tuberculosis patients, further studies would be required.

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AN IMMUNOHISTOCHEMICAL STUDY ON ANTI-T LYMPHOCYTE MONOCLONE ANTIBODY AFTER AUTOGENOUS FULL-THICKNESS SKIN GRAFT IN RAT (백서에서 자가 피부이식후 항 T임파구 단일클론항체 분포에 관한 면역조직화학적 연구)

  • Park, Man-Kyu;Kim, Kyung-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.13 no.4
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    • pp.370-380
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    • 1991
  • This article is intended to study histopathological and immunohistochemical response after autogenous full-thickenss skin graft in rat. 12 male Sprague-Dawley rats were used as the experimental animals. A $1Cm{\times}1Cm$ skin(0.7mm diameter) was taken on the right inguinal area of the rat. Another full-thickeness skin graft($1Cm{\times}1Cm$) was taken from the left inguinal area of the rat. And it was transplanted to the right inguinal area of the rat. The left side wound was closed directly. Light microscopic observation was made at the postoperative $1^{\circ}3^{\circ}8^{\circ}16$ day, after the hematoxylin - Eosin staining of the 4u-thick paraffin embedded specimens and the immunoshitochemical staining of the 10u-thick frozen specimens with mouse anti-rat monoclone antibodies and ABC staining kit. The results were as follows. 1. Electromicroscopic studies revealed interstitial tissue bleeding of transplanted autogenous skin. The response was severe in the 1 day group after operation, moederate in 3 day group, mild in 8 day group, and almost resovled in the 16 days group. 2. Electromicrospic studied also revealed a mild monocyte response in the 3 day and 8 day group. A histiocytic infiltrate was observed. There was a mild response in the 3 day group and moderate response in the 8 day group. 3. Immunohistochmically studies revealed a few pan T cells in the 1 day group, mild appearance of pen T cells and cytotoxic T cells in the 3 day group, a moderate infiltrate of pan T cells and helper T cells in the 8 day group, and total resolution of pan T cells in the 16 day group. 4. According to these finding, a strong inflammatory response was observed around transplanted autogenous skin in the 3 & 8 day groups. In the 16 day group this response had resolved histopathologically and immunohistologically.

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Studies on Immuno-Modulatory and Antitumor Effects of Crude Polysaccharides Extracted from Paecilomyces sinclairii (매미눈꽃동충하초(Paecilomyces sinclairii)로부터 추출한 조다당류의 면역 활성과 항암 효과에 관한 연구)

  • Shim, Sung-Mi;Im, Kyung-Hoan;Lee, U-Youn;Kim, Jung-Wan;Shim, Mi-Ja;Lee, Min-Woong;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.31 no.3
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    • pp.155-160
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    • 2003
  • Neutral salt soluble [0.9% NaCl (Fr. NaCl)], hot water soluble (Fr. HW) and methanol soluble (Fr. MeOH) materials were extracted from Paecilomyces sinclairii. In vitro cytotoxicity tests. Fr. HW was not cytotoxic against MH3T3, Sarcoma 180 and HepG2 cancer cell lines at the concentration of $0{\sim}2,000\;{\mu}g/ml$, while HT-29 cell line was cytotoxic at the concentration of $100\;{\mu}g/ml$. Fr. NaCl and Fr. MeOH were slightly cytotoxic to the cell lines. Intraperitoneal injection with Fr. NaCl and Fr. MeOH exhibited antitumor activity with life prolongation effect of 32.3% in mice inoculated with Sarcoma 180. Fr. NaCl improved proliferation of spleen cells and the immunopotentiation activity of B lymphocyte by increasing spleen cell numbers and the alkaline phosphatase activity by $2.4{\sim}2.6\;and\;2.7{\sim}3.9$ folds, respectively. Fr. NaCl generated $89\;{\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of $50\;{\mu}g/ml$, while iipopolysaccharide, a positive control, produced $79\;{\mu}M$. The Fr. NaCl showed the hightest antitumor effect and activation of B lymphocytes and macrophage. From these results, antitumor effect of P. sinclaitii was likely due to immunopotentiation activity.

Enhancement of cell-mediated immunity by administration of plasma protein in pigs 2. Proportion of T lymphocyte subpopulations and cells expressing MHC class I, II molecules in peripheral blood (돼지에서 plasma protein에 의한 세포성면역 증진효과에 관한 연구 2. 혈액내 T 림프구 아군 및 MHC class 세포의 분포율)

  • Yang, Chang-kun;Kim, Soon-jae;Moon, Jin-san;Jung, Suk-chan;Park, Yong-ho
    • Korean Journal of Veterinary Research
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    • v.34 no.2
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    • pp.287-299
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    • 1994
  • Plasma protein which has been known as one of nonspecific immunostimulators was added to feedstuff to examine its effect on the enhancement of cellular immune response in porcine immune system. A total of 40 piglets, 20 male and 20 female each, were fed for 30 days with or without plasma protein. The peripheral blood were collected and analyzed for the investigation of leukocyte subpopulations and their activities by using a panel of monoclonal antibodies specific to porcine leukocyte differentiation antigens and flow cytometry. The results obtained as follows. 1. Subpopulations expressing major histocompatibility complex(MHC) class I antigen were $96.2{\pm}3.1%$ and $86.6{\pm}3.8%$ in piglets fed with plasma protein and in piglets fed without plasma protein, respectively. 2. Proportion of leukocyte subpopulation expressing MHC class II antigens were significantly higher in the piglets fed with plasma protein than ones without plasma protein. The proportion was $27.6{\pm}3.6%$ and $16.6{\pm}2.2%$ in MHC class II DQ antigen, and $28.1{\pm}2.0%$ and $20.0{\pm}0.3%$ in MHC class II DR antigen, respectively. 3. A significant increase in the proportion of cells expressing poCD2 was not found in piglets fed plasma protein. 4. Proportion of subpopulation expressed porcine(Po) CD4 antigens which specific to helper T lymphocytes were not increased (18.3-19.1% vs. 25.6-28.8%), rather slightly decreased, in plasma protein-treated group. 5. The most important increase of proportion in plasma protein-treated group was the leukocyte subpopulation specific to $poCD8^+$ T cytotoxic/suppressor lymphocytes. The expression level was significantly higher up to 45.9-47.1% in plasma protein-treated group in comparing with 29.7-33.0% in non-plasma protein-treated group. 6. Lymphoblastogenetic responses using different concentrations of Con A mitogen and plasma protein has found that the responses of lymphocyte from piglets fed plasma protein was significantly activated (p<0.01). The activities measured by 3[H]-thymidine incorporation showed 3-6 times stronger in plasma protein-treated group than those in non-plasma protein-treated group. The study has concluded that plasma protein, which has known as a nonspecific immunostimulator, may have an immunoenhancing activities in porcine lymphoid system by increase the activated cell proportions and their blastogenetic properties which is critical to host immune responses.

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