• Title/Summary/Keyword: CTL

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Long-Term Annual Trend Analysis of Epilimnetic Water Quality and Their Longitudinal Heterogeneities in Lake Soyang (소양호 표층수 수질의 연별 추이 및 상 ${\cdot}$ 하류 이질성 분석)

  • Lee, Hye-Won;An, Kwang-Guk;Park, Seok-Soon
    • Korean Journal of Ecology and Environment
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    • v.35 no.1 s.97
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    • pp.36-44
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    • 2002
  • The spatial and temporal trends of water qualities in Lake Soyang was statistically analyzed in this study. The water qualities include nutrients, ionic contents and chlorophyll-a (Chl-a) measured during 1993${\sim}$2000. The rainfall intensity and runoff from the catchment appeared to play an important role in water quality trends in the lake. According to seasonal Mann-Kendall test, conductivity, TP, and Ctl-a did not show any trends of increase or decrease over the 8 year period, while TN declined slightly. It was found that the variation of TP was a function of interannual inflow and rainfall. In the analyses of spatial trend, conductivity, based on the mean by site, showed a downlake decline over the eight year period. Minimum conductivity was found in the headwaters during summer monsoon of July to August and near the dam during October. This result indicates a time-lag phenomenon that the headwater is diluted by rainwater immediately after summer monsoon rain and then the lake water near the dam is completely diluted in October. During summer period, TP and TN had an inverse relation with conductivity values. Concentrations of TP peaked during July to September in the headwaters and during September in the downlake. Also, TN increase during the summer and was more than 1.5 mg/L regardless of season and location, indicating a consistent eutrophic state. Values of Chl-a varied depending on location and season, but peaked in the midlake rather than in the headwaters during the monsoon. Regression analyses of log-transformed seasonal Chl-a against TP showed that value of $R^2$ was below 0.003 in the premonsoon and monsoon seasons but was 0.82 during the postmonsoon, indicating a greater algal response to the phosphorus during the postmonsoon. In contrast, TN had no any relations with Chl-a during all seasons.

Comparison of immune cell populations in bronchoalveolar lavage cells and PBMC cytokine expressions in porcine reproductive and respiratory syndrome and porcine respiratory disease complex

  • Yang, Myeon-Sik;Jeong, Chang-Gi;Nazki, Salik;Mattoo, Sameer ul Salam;Lee, Sang-Myeong;Kim, Won-Il;Kim, Bumseok
    • Korean Journal of Veterinary Service
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    • v.42 no.4
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    • pp.201-216
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    • 2019
  • Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory distress in all age pigs. Porcine respiratory disease complex (PRDC) is a disease caused by opportunistic bacterial infection secondary to a weakened immune system by a preceding respiratory infection. In this study, we tried to compare the immune responses in PRRS and PRDC groups to clearly characterize the disease severity. Eighty-five pigs were infected with various Korean field PRRS virus strains. Infected animals were classified into PRRS (n=32) and PRDC (n=53) groups based on lung lesions such as interstitial pneumonia, suppurative pneumonia, and pleuropneumonia. The immune cell population of bronchoalveolar lavage cells (BALc) was evaluated on 14 and 28 days post infection (dpi) and PMBC cytokine expression was measured on 0, 3, 7, 14 dpi to investigate early inflammatory reactions. Pulmonary lesion severity was negatively correlated with alveolar macrophage (AM) in both PRRS and PRDC groups on 14 and 28 dpi. AM in BALc was less populated in PRDC group on 28 dpi compared to PRRS group. AM in BALc was significantly less populated in PRDC group on 28 dpi compared to 14 dpi. In addition, cytotoxic T lymphocyte (CTL) in BALc was higher populated in PRDC group on 14 dpi and 28 dpi compared to PRRS group. In the case of PBMC cytokine TNF-α, IFN-α, IL-1β, IFN-γ, FoxP3, and IL-2, the PRRS group showed higher expression than the PRDC group on 7 dpi, 14 dpi, 7 dpi, 14 dpi, 14 dpi, and 14 dpi, respectively. On the other hand, in the case of IFN-β, IL-6, IL-8, IL-4, and IL-17, the PRDC group showed higher PBMC cytokine expression at 14 dpi, 7 dpi, 14 dpi, 3 dpi, and 3 dpi, respectively, than the PRRS group. Based on these results, our study could characterize differential immune responses in pigs with PRRS or PRDC.

Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine

  • Lee, Jun-Sik;Kim, Dae-Hyun;Lee, Chang-Min;Ha, Tae-Kwun;Noh, Kyung-Tae;Park, Jin-Wook;Heo, Deok-Rim;Son, Kwang-Hee;Jung, In-Duk;Lee, Eun-Kyung;Shin, Yong-Kyoo;Ahn, Soon-Cheol;Park, Yeong-Min
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.79-94
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    • 2011
  • Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

B Cells Transduced with HPV16 E6/E7-expressing Adenoviral Vector Can Efficiently Induce CTL-dependent Anti-Tumor Immunity

  • Kim, Yun-Sun;Ko, Hyun-Jeong;Kim, Yeon-Jeong;Han, Seung-Hee;Lee, Jung-Mi;Chang, Woo-Sung;Jin, Hyun-Tak;Sung, Young-Chul;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.7 no.3
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    • pp.109-116
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    • 2007
  • Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

Gene Therapy Using GM-CSF Gene Transferred by a Defective Infectious Single-cycle Herpes Virus in Micro-residual Organotropic Head and Neck Squamous Cell Cancer Model (향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료)

  • Kim Se-Heon;Choi Eun-Chang;Kim Han-Su;Chang Jung-Hyun;Kim Ji-Hoon;Kim Kwang-Moon
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.1
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    • pp.25-33
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    • 2003
  • Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

Respiratory Protective Effect of a RML on PM10D-induced Lung Injury Mouse Model (미세먼지 유발 폐기능 손상 동물모델에서 RML의 호흡기 보호 효과)

  • Kim, Soo Hyun;Kim, Min Ju;Shin, Mi-Rae;Roh, Seong-Soo;Kim, Seung Hyung;Park, Hae-Jin
    • The Korea Journal of Herbology
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    • v.37 no.3
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    • pp.29-39
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    • 2022
  • Objective : This study is aimed to evaluate the protective effects of Rehmanniae Radix, Mori Folium, and Liriopie Tuber mixture (RML) on lung injury of Particulate matter less than 10 um in diameter and diesel exhaust particles (PM10D) mice model. Methods : To investigate the anti-inflammatory activity of RML, PM10D was diluted in aluminum hydroxide (Alum) in 7-week-old male mice and induced by Intra-Nazal-Tracheal (INT) injection method. Animal experiments were divided into 5 groups. Nor (normal mice), CTL (PM10D-induced mice with the administration of distilled water), DEXA (PM10D-induced mice with the administration of 3 mg/kg Dexamethasone), RML 100 (PM10D-induced mice treated with RML 100 mg/kg weight), and RML 200 (PM10D-induced mice treated with RML 200 mg/kg body weight). After 11 days administration, mice were sacrificed and inflammation-related immune cells in broncho-alveolar lavage fluid (BALF) were analyzed. Inflammation-related biomarkers were also analyzed in blood and lungs. Lung tissue was observed through histological examination. Results : In the PM10D induced model, the PML showed decreases in CXCL-1 and IL-17A in BALF. Expression of inflammatory cytokines and cough-related mRNA genes was significantly decreased in serum and lung tissue. The mixture treatment of RML significantly improved the immune related cells in the serum. In addition, histological observations showed a tendency to decrease the severity of lung injury. Conclusions : Overall, these results confirmed the respiratory protective effect of the RML mixture in a model of lung injury induced by air pollution (PM10+DEP), suggesting that it is a potential treatment for respiratory damage.

Efficient Anti-Tumor Immunotherapy Using Tumor Epitope-Coated Biodegradable Nanoparticles Combined With Polyinosinic-Polycytidylic Acid and an Anti-PD1 Monoclonal Antibody

  • Sang-Hyun Kim;Ji-Hyun Park;Sun-Jae Lee;Hee-Sung Lee;Jae-Kyung Jung;Young-Ran Lee;Hyun-Il Cho;Jeong-Ki Kim;Kyungjae Kim;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.42.1-42.20
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    • 2022
  • Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2Kb mAbs, and then attached to H-2Kb molecules isolated from the tumor mass (H-2b). Native peptides associated with the H-2Kb molecules of H-2Kb-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8+ T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

  • Dong Hyun Kim;Hee Young Kim;Won-Woo Lee
    • IMMUNE NETWORK
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    • v.21 no.5
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    • pp.33.1-33.19
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    • 2021
  • IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8+ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8+ T cells and features of IL-1R+ CD8+ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8+ T cells. Further, IL-1β enhances the effector function of CD8+ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8+ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8+ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8+ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

Usability Evaluation of Applied Low-dose CT When Examining Urinary Calculus Using Computed Tomography (컴퓨터 단층촬영을 이용한 요로결석 검사에서 저선량 CT의 적용에 대한 유용성 평가)

  • Kim, Hyeon-Jin;Ji, Tae-Jeong
    • The Journal of the Korea Contents Association
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    • v.17 no.6
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    • pp.81-85
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    • 2017
  • The aim of this study was to evaluate the usability of applied Low dose Computed Tomography(LDCT) protocol in examining urinary calculus using computed tomography. The subjects of this study were urological patients who visited a medical institution located in Busan from June to December 2016 and the protocol used in this study was Adaptive Statistical Iterative Reconstruction: low-dose CT with 50% Adaptive Statistical Iterative Reconstruction (ASIR). As results of quantitative analysis, the mean pixel value and standard deviation within kidney region of image(ROI)of the axial image were $26.21{\pm}7.08$ in abdomen CT pre scan and $20.03{\pm}8.16$ in low-dose CT. Also the mean pixel value and standard deviation within kidney ROI of the coronal image were $22.07{\pm}7.35$ in abdomen CT pre scan and $21.67{\pm}6.11$ in low dose CT. The results of qualitative analysis showed that four raters' mean values of observed kidney artifacts were $19.14{\pm}0.36$ when using abdomen CT protocol and $19.17{\pm}0.43$ in low-dose CT, and the mean value of resolution and contrast was $19.35{\pm}0.70$ when using abdomen CT protocol and $19.29{\pm}0.58$ in low-dose CT. Also the results of a exposure dose analysis showed that the mean values of CTDIvol and DLP in abdomen CT pre scan were 18.02 mGy and $887.51mGy{\cdot}cm$ respectively and the mean values of CTDIvol and DLP when using low-dose CT protocol were 7.412 mGy and $361.22mGy{\cdot}cm$ respectively. The resulting dose reduction rate was 58.82% and 59.29%, respectively.

The Antioxidant Activity of Yacon (Polymnia sonchifoliaty) and its Application to the Pork Patties as a Natural Antioxidant (야콘 착즙액의 항산화 활성 및 천연 항산화제로서 돈육패티에 이용)

  • Park, Jin-Sun;Kim, Hyeong-Sang;Chin, Koo-Bok
    • Food Science of Animal Resources
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    • v.32 no.2
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    • pp.190-197
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    • 2012
  • This study was performed to evaluate the extraction method (Yacon ethanol extracts; YEE, Yacon pressed extracts; YPE) and various levels (0.05-1.0%) of Yacon (Polymnia sonchifolia) on antioxidant and antimicrobial activities. In linoleic acid emulsion of YPE, there were higher iron chelation activity and antioxidant activity than those of YEE (p<0.05). A 1,1- diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity and reducing power of both extracts showed a higher rate at 0.5% level. Ground pork patties, which contain 0.5% YEE and YPE, were manufactured and BHT (0.01%) was used as a reference. Physicochemical properties and microbial counts of ground pork patties, containing a different type of Yacon, were evaluated during the 14 d of storage at $4^{\circ}C$. A pH level, and lightness (Hunter L), as well as the yellowness (Hunter b) values of treatments were not different from those of the control (p>0.05), but increased during storage, at $4^{\circ}C$. Lightness values of ground pork patties, with Yacon extracts, showed the highest. TBARS value of ground pork patties that contains Yacon increased with increased storage at $4^{\circ}C$ (p<0.05), and pork patties with YPE or YEE retarded the lipid oxidation, during refrigerated storage, as compared to that of the CTL. Thus, YPE could be used as a potential possibility to inhibit the lipid oxidation of processed meats, during the refrigerated storage.