• Title/Summary/Keyword: CTL

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Simplification of State Invariant with Mixed Reachability Analysis (혼합 도달성 분석을 이용한 상태 불변식의 단순화)

  • 권기현
    • Journal of KIISE:Software and Applications
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    • v.30 no.3_4
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    • pp.212-218
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    • 2003
  • State invariant is a property that holds in every reachable state. It can be used not only in understanding and analyzing complex software systems, but it can also be used for system verifications such as checking safety, liveness, and consistency. For these reasons, there are many vital researches for deriving state invariant from finite state machine models. In previous works every reachable state is to be considered to generate state invariant. Thus it is likely to be too complex for the user to understand. This paper seeks to answer the question `how to simplify state invariant\ulcorner`. Since the complexity of state invariant is strongly dependent upon the size of states to be considered, so the smaller the set of states to be considered is, the shorter the length of state invariant is. For doing so, we let the user focus on some interested scopes rather than a whole state space in a model. Computation Tree Logic(CTL) is used to specify scopes in which he/she is interested. Given a scope in CTL, mixed reachability analysis is used to find out a set of states inside it. Obviously, a set of states calculated in this way is a subset of every reachable state. Therefore, we give a weaker, but comprehensible, state invariant.

IL-12 Production and Subsequent Natural Killer Cell Activation by Necrotic Tumor Cell-loaded Dendritic Cells in Therapeutic Vaccinations

  • Kim, Aeyung;Kim, Kwang Dong;Choi, Seung-Chul;Jeong, Moon-Jin;Lee, Hee Gu;Choe, Yong-Kyung;Paik, Sang-Gi;Lim, Jong-Seok
    • IMMUNE NETWORK
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    • v.3 no.3
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    • pp.188-200
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    • 2003
  • Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.

T 임파구와 세포성면역

  • 최철순
    • Journal of the korean veterinary medical association
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    • v.25 no.10
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    • pp.595-606
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    • 1989
  • 항원제시세포(APC)와 보조T세포 간의 협력작용에 의하여 활성화된 작동세포(NK세포, CTL, K세포, 대식세포, 과립구 등)의 종양세포, 이식장기 및 세포내기생세균에 감염된 각종 세포에 대한 세포독성작용은 생체방어를 위한 중요한 세포성면역기전이다. 지난 몇 년간 세포성면역기전에 관한 많은 연구에도 불구하고 T림파구매개성 세포독성작용의 면역생물학적기전은 확실히 밝혀있지 않다. 지금까지 알려진 중요한 연구내용을 요약하면 다음과 같다. 1. 세포독성작용을 나타내는 작동세포로는 NK세포, CTL, K세포, 대식세포/단핵구 및 과립구가 있다. 2. T세포의 세포표면항원분자군(CD)으로는 $CD_{2},\;CD_{3},\;CD_{4}[Ly_{3}T_{4}],\;CD_{5}[=Ly_{1}],\;CD_{7},\;CD_{8}[Ly_{2,3}]$가 있으며 $CD_{4}$는 보조Ttpvhdml 특이마커이고 $CD_{8}$는 세포독성 T세포 및 억압T세포의 특이마커이다. 주요 T세포수용체(TCR)는 $CD_{4}$ 또는 $CD_{8}$ 분자와 가까이 연합된 이향체($TCR-{\alpha}{\beta}/TCR-{\gamma}{\delta}$이며 보조 T세포 $CD_{4}$(마우스 $L_{3}T_{4}$)는 수용체와 연합되어 있는반면 억압 T세포 $CD_{8}(Ly+_{2,3})$는 항원수용체와 연합되어 있다. 3. T세포는 Ti-$CD_{3}$(항원/MHC) 복합체를 통한 '항원가교'에 의한 자극(항원인식)과 $CD_{2}$를 통한 비특이경로에 의하여 활성화(분화증식)된다. 비특이경로를 통한 활성경로에서 T세포($CD_{4}$$CD_{8}$)가 활성화되기 위하여는 보조T세포가 생산하는 IL-2을 요구하며 IL-2의 자극으로 분화증식된 $CD_{8}$는 세포독성능을 나타내지만 $CD_{4}^{+}$는 여전히 세포독성능을 나타내지 못한다. 4. 보조T세포는 class II MHC분자와 연합된 항원을 식별하는 반면 세포독성T세포는 class I MHC 분자와 연합된 항원을 식별한다. 5. 림파구 매개성 세포독성은 접촉(conjugati-on), 탈분극(depolarization), 용해계획(progra-mming), 용해(lysis) 및 재순환(recycling)의 단계를 거쳐 진행된다. 6. 표적세포살해매체로는 perforin / PFP / cy-tolysin, lymphopores, lymphotoxins, protone, cytolytic enzymes가 알려졌으며 세포독성작용은 이들 이외에도 여러 가지 매체를 통한 복합작용으로 추정된다. 7. CTL 매개성 표적세포의 주요 대사변화는 actomyocin ATPase의 증가, phosphocreatine과 ATPase의 소모, ATP 의존성 $Na^{+}/K^{+}$ 펌프작용의 중지, ATP 의존성 $Ca^{2+}$ 유출감소 및 세포내 축적이 관찰된다. 8. $Ca^{2+}$의 축적으로 세포막 교질 침투손상을 주어 수분의 유입을 증가시킴으로써 수포형성, 핵붕괴, 사립체팽화 및 정상세포 구조상실(Zeiosis)이 있다. 결론적으로 CTL 매개성 세포독성작용은 PFP, LT, TNF, 유사 TNF / LT 및 기타 매체를 통한 복합작용이며 세포살해기전은 지속적 대사소모와 정형적 세포구조(핵 및 세포질)의 파괴에 의한 것이다.

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Evaluation of Sodium Lactate and Potassium Lactate on the Quality Characteristics and Shelf-life of Low-fat Sausage during Refrigerated Storage (젖산나트륨과 젖산칼륨의 첨가가 냉동저장 중 저지방 소시지의 품질특성 및 저장성에 미치는 영향)

  • Chin Koo Bok;Ahn Eun Ha
    • Food Science of Animal Resources
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    • v.25 no.1
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    • pp.52-59
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    • 2005
  • This study was performed to investigate physicochemical and textural characteristics, and antimicrobial effect for Listeria monocytogenes (LM) in low-fat functional sausages (LFFS) containing sodium lactate (SL) and potassium lactate (PL) during storage at 4℃ for 10 weeks. The LFFS treatments included CTL (Low-fat sausage control), TRT1 (SL 3.3%), TRT2 (SL 2.2% + PL 1.1%), TRT3 (SL 1.1% + PL 2.2%), TRT4 (PL 3.3%). Proximate composition for LFFS were 73.9∼75.2% moisture, 1∼2% fat and 15.5∼15.9% protein, and pH values ranged from 5.8 to 6.5. Expressible moisture (EM, %) and vacuum purge (VP, %) ranged from 22.9 to 33.0 and from 2.7 to 5.3, respectively. EM of CTL, TRT1 and TRT2 increased with increased storage time, however, no differences in VP were observed during storage time. Hunter color values (L, a, b) were not affected by the addition of SL and PL, and storage time (p>0.05). Most textural properties of LFFS were not affected by the addition of SL and PL, except for few cases, but those of CTL tended to increase with increased storage time. The addition of SL and PL into LFFS, alone or in combination, inhibited the microbial growth of inoculated LM during refrigerated storage, resulting in longer shelf-life than the control.

Development and Validation of a Simple Index Based on Non-Enhanced CT and Clinical Factors for Prediction of Non-Alcoholic Fatty Liver Disease

  • Yura Ahn;Sung-Cheol Yun;Seung Soo Lee;Jung Hee Son;Sora Jo;Jieun Byun;Yu Sub Sung;Ho Sung Kim;Eun Sil Yu
    • Korean Journal of Radiology
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    • v.21 no.4
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    • pp.413-421
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    • 2020
  • Objective: A widely applicable, non-invasive screening method for non-alcoholic fatty liver disease (NAFLD) is needed. We aimed to develop and validate an index combining computed tomography (CT) and routine clinical data for screening for NAFLD in a large cohort of adults with pathologically proven NAFLD. Materials and Methods: This retrospective study included 2218 living liver donors who had undergone liver biopsy and CT within a span of 3 days. Donors were randomized 2:1 into development and test cohorts. CTL-S was measured by subtracting splenic attenuation from hepatic attenuation on non-enhanced CT. Multivariable logistic regression analysis of the development cohort was utilized to develop a clinical-CT index predicting pathologically proven NAFLD. The diagnostic performance was evaluated by analyzing the areas under the receiver operating characteristic curve (AUC). The cutoffs for the clinical-CT index were determined for 90% sensitivity and 90% specificity in the development cohort, and their diagnostic performance was evaluated in the test cohort. Results: The clinical-CT index included CTL-S, body mass index, and aspartate transaminase and triglyceride concentrations. In the test cohort, the clinical-CT index (AUC, 0.81) outperformed CTL-S (0.74; p < 0.001) and clinical indices (0.73-0.75; p < 0.001) in diagnosing NAFLD. A cutoff of ≥ 46 had a sensitivity of 89% and a specificity of 41%, whereas a cutoff of ≥ 56.5 had a sensitivity of 57% and a specificity of 89%. Conclusion: The clinical-CT index is more accurate than CTL-S and clinical indices alone for the diagnosis of NAFLD and may be clinically useful in screening for NAFLD.

A Case Study on Operational Strategy for CTL in College (전문대학 교수학습지원센터의 운영 전략 사례 연구)

  • Choi, seok-hyun
    • Proceedings of the Korea Contents Association Conference
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    • 2018.05a
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    • pp.425-426
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    • 2018
  • 본 연구는 전문대학 교수학습지원센터의 운영 전략 사례를 통해 우수 교수학습지원센터의 특징을 밝히고 4차 산업혁명 시대를 대비한 교수학습의 질 제고와 교수학습지원센터의 발전 방안을 제시하고자 하였다.

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Induction of Cytotoxic T Lymphocyte Response against the Core and NS3 Genes of the Hepatitis C Virus in Balb/c Mice

  • Kim, Na-Young;Sohn, He-Kwang;Choe, Joon-Ho;Park, Sang-Dai;Seong, Rho-Hyun
    • Animal cells and systems
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    • v.3 no.3
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    • pp.337-341
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    • 1999
  • Hepatitis C virus (HCV) is a positive strand RNA virus of the Flaviviridae family and the major cause of post-transfusion non-A, non-B hepatitis. Vaccine development for HCV is essential but has been slowed by poor understanding of the type of immunity that naturally terminates HCV infection. The DNA-based immunization technique offers the potential advantage of including cellular immune responses against conserved internal proteins of a virus, as well as the generation of antibodies to viral surface proteins. Here, we demonstrate that cell lines expressing the HCV core and/or NS3 proteins can induce a specific CTL response in mice, and these results suggest a possibility that the HCV core and NS3 DNA can be used to induce CTL activity against the antigen in mice and can be further developed as a therapeutic and preventive DNA vaccine.

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Immunomodulatory activity of phytoprotein isol Acanthopanax senticosus : Regulation of CTL responses and activation of macrop

  • Lee Seok Won;Lee Soo Jin;Park Jeon Ran;Kim Ha na;Ahn Kyoo Seok;Kim Jung-Hyo;Baek Nam-in;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.1
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    • pp.230-235
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    • 2004
  • We previously reported that the phytoprotein extracted from Acanthopanax senticosus (PA) had anti-carcinogenic anti-metastatic activity via increase of inhibition of gap junctional intercellular communication. In the present study investigated the immunomodulatory mechanism of phytoprotein isolated from the stem bark of Acanthopanax sentic (PA). PA was found to significantly stimulate macrophages producing TNF-α and IL-1β in vitro. It also showed tumori activity indicating that PA had the ability to stimulate macrophage directly. Moreover, PA induced the CDB/sup +/ CTL cy responses to recognize antigen on the B16-BL6 melanoma cells. Treatment of PA with B16-BL6 melanoma cells increased the proliferation of splenocytes compared with untreated control. These results demonstrate that PA immunomodulatory activity suggesting a useful anti-tumor agent applicable to treatment and prevention of cancer.

The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity (항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건)

  • Nam, Byung-Hyouk;Jo, Wool-Soon;Lee, Ki-Won;Oh, Su-Jung;Kang, Eun-Young;Choi, Yu-Jin;Do, Eun-Ju;Hong, Sook-Hee;Lim, Young-Jin;Kim, Ki-Uk;Jeong, Min-Ho
    • Journal of Life Science
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    • v.16 no.6
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    • pp.904-910
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    • 2006
  • Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.