• Title/Summary/Keyword: $CD8^+$ T cell

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Expression of Epstein-Barr Virus Gene and Clonality of Infiltrated T Lymphocytes in Epstein-Barr Virus-associated Gastric Carcinoma

  • Lee, Jae-Myun;Kim, Ho-Guen;Noh, Sung-Hoon;Lee, Won-Young;Kim, Se-Jong;Park, Jeon-Han
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.50-58
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    • 2011
  • Background: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. Methods: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. Results: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. $CD8^+$ T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR $V{\beta}$ CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. Conclusion: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.

Evaluation of a Streptococcus pneumoniae DNA Vaccine Efficacy (폐렴구균 DNA 백신의 유효성 평가)

  • Lee Jue-Hee;Han Yongmoon
    • YAKHAK HOEJI
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    • v.49 no.6
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    • pp.484-489
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    • 2005
  • Streptococcus pmeumoniae is the leading cause of pneumonia and bacterial meningitis. The current polysaccharide vaccine has been reported ineffective in elderly adults and children less than 2 years of age. Thus, in recent many researchers have been focused on a different approach, DNA vaccine. In our laboratory we developed a Streptococcus pneumoniae DNA (SPDNA) vaccine. This SPDNA vaccine was formulated by inserting the region encoding part of the capsule in the S. pneumoniae into the LAMP-1. In present work, with use of the SPDNA vaccine we attempted to establish a certain methodology useful for evaluation of effectiveness and immunoresponse of a DNA vaccine. Results showed that the subcutaneous route was the most effective for production of antisera specific for S. pneumoniae in mice. By isotyping analyses, IgM, IgGl, IgG2a, and IgG2b were determined. In addition, INF-$\gamma$ and IL-4 were predominantly detected. Combination of those data resulted in a pattern of IgGl < IgG2a=IgG2b and INF$\gamma\>$ >IL-4, which indicates the inmmunity towards the Thl response predominantly; furthermore, the SPDNA vaccination induced resistance of the CD4+T lymphocyte-depleted mice against disseminated pneumococcal infection. These data appear to be possibly due to activation of CDS8+T cell-activation. Taken together, this methodology can be applied for evaluating efficacy and mode of action of a DNA vaccine as minimum critera.

Effects of Hyperosmolar Stimuli on Activation of Human Eosinophilic Leukaemia EoL-1 Cells (고삼투압 자극이 호산구의 활성화에 미치는 영향)

  • Kwon, Byoung Chul;Kim, Eun Soo;Kim, Kyung Won;Song, Tae Won;Sohn, Myung Hyun;Shin, Myeong Heon;Kim, Kyu-Eam
    • Clinical and Experimental Pediatrics
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    • v.48 no.8
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    • pp.881-885
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    • 2005
  • Purpose : Airway dehydration and subsequent hyperosmolarity of periciliary fluid are considered critical events in exercise-induced bronchoconstriction. The aim of this study was to establish if a hyperosmolar challenge could induce activation of eosinophils. Methods : Human eosinophilic leukaemic cell lines, EoL-1 cells were incubated with hyperosmolar solutions for 15 minutes. Activation of EoL-1 cells was monitored by degranulation and superoxide anion production. In addition, we examined surface expression of CD69 and ICAM-1. Results : Hyperosmolar stimuli didn't induce superoxide anion production and degranulation. In addition, EoL-1 cells cultured with hyperosmolar medium at 930 mOsm/kg $H_2O$ resulted in no significant increment in fluorescent intensity of CD69 and ICAM-1 expression compared with results for cells incubated with isomolar medium. Conclusion : We found that hyperosmolar stimuli don't cause activation of EoL-1 cells, but further studies are required to determine the role of eosinophil in the mechanism of exercise-induced asthma.

Male to Female Heterosexual Transmission of HIV in Korea: Transmission Rate and Risk Factors (이성간 성접촉을 통한 HIV 전파율과 위험인자에 관한 연구: 남성으로부터 여성으로의 전파)

  • Go, Un-Yeong;Kee, Mee-Kyung;Choi, Byeong-Sun;Kang, Chun;Do, Kyoung-Mee;Lee, Ju-Hyun;Lee, Joo-Shil
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.2
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    • pp.228-235
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    • 1999
  • Objectives: Despite the importance of human immunodeficiency virus(HIV) transmission through heterosexual contact, the features of heterosexual transmission has not been well studied in Korea. So we conducted a cross sectional study to determine the transmission rates in married couples and assess risk factors for male to female heterosexual transmission of HIV. Methods: 169 HIV-infected males and their female sex partners were recruited from 1985 to tune 1998. We examined female sex partner's HIV infection status and interviewed male index partners and their female sex partners about demographic characteristics and sexual practices. We analysed heterosexual transmission rate by epidemiologic characteristics, disease status and sexual practices. And we assessed risk factors for HIV infection by univariate and multivariate analysis. Results: 30 female sex partners were infected at enrollment, yielding an transmission rate of 17.8%. Among couples who had used condoms consistently, none of the female sex partners was infected with HIV. In univariate analysis the significant risk factors were full blown AIDS status (OR=4.1, 95% CI: 1.49-11.43) and low CD4 T cell count of index partners at enrollment (OR=7.8, 95% CI: 2.19-27.80). In multivariate analysis HIV-1 RNA levels was significant risk factor when adjusted by CD4 T cell courts and mean sexual contacts per month (OR=19.2, 95% CI: 1.03-357.59) Conclusion: The risk of male to female heterosexual transmission increased with advanced stages of HIV infection in the index male partners.

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Effects of Boyangmaksung-bang (BYMSB) on the Membranous Nephropathy Induced by Cationic Bovine Serum Albumin in Mouse Model (보양막성방(補陽膜性方)이 Cationic Boivine Serum Albumin 투여로 유발된 Mouse의 Membranous Nephropathy에 미치는 영향)

  • Lim, Bum-Soo;Cho, Chung-Sik;Kim, Cheol-Jung
    • The Journal of Korean Medicine
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    • v.30 no.2
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    • pp.63-78
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    • 2009
  • Objective: The purpose of experimental study was to prove the effects of Boyangmakseong-bang (BYMSB) treatment on cBSA-induced in a MN mouse model. Methods: We divided mice into 4 groups. The Normal group had no treatment. We used cBSA and induced MN mouse model to the other 3 groups. The Control group was treated with cBSA (9mg/kg i.p) only. The second group, named 'BY-250', was treated with cBSA (9mg/kg i.p) and BYMSB extract (250mg/kg, p.o). The third group, named 'BY-500', was treated with cBSA (9mg/kg i.p) and BYMSB extract (500mg/kg, p.o). After cBSA and BYMSB extract treatment for 4 weeks, the increase in percentage of body weight, proteinuria, serum albumin, total cholesterol, creatinine and BUN of all groups were measured. The CD3+, CD19+, CD4+, CD8+ cell levels of spleen of all groups were analyzed. IgA, IgG, IgM, IL-$1{\beta}$, TNF-${\alpha}$, IL-6 and IFN-${\gamma}$ levels of all groups were gauged. H&E staining, immunofluorescence staining and electron microscopy of kidney were observed. Results: BYMSB showed significant decrease in the 24hrs proteinuria, serum total cholesterol, serum IgG levels and BUN levels, and showed significant increase in the serum albumin levels compared with the control group. BYMSB showed increase in the increasing percentage of body weight and IFN-${\gamma}$ levels compared with the control. BYMSB showed decrease in the CD3+ T cells, CD4+ Th cells, IL-$1{\beta}$, TNF-${\alpha}$ and IL-6 levels, but did not show significant change compared with the control. BYMSB showed considerable decrease in the thickening of the GBM on H&E staining, deposition of IgG on immunofluorescence staining and deposition of electron-density on electron microscopy of kidney compared with the control. Conclusions: According to the above results, it is suggested that BYMSB decreases the symptoms of MN induced by cBSA in a mouse model. Therefore BYMSB seems to be applicable to MN in clinical practice.

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Bioinformatic analyses reveal the prognostic significance and potential role of ankyrin 3 (ANK3) in kidney renal clear cell carcinoma

  • Keerakarn Somsuan;Siripat Aluksanasuwan
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.22.1-22.15
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    • 2023
  • Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

IL-4-deficient Mice Aggravate Hypersensitivity Pneumonitis

  • Hwang, Su-Jin;Chung, Doo-Hyun
    • IMMUNE NETWORK
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    • v.8 no.3
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    • pp.90-97
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    • 2008
  • Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

Effect of Dried Powders and Water Extracts of Paecilomyces Tenuipes and Cordyceps Militaris on Lipid Metabolism, Antioxidative Capacity and Immune Status in Rats (동충하초의 건분 및 물추출물이 흰쥐의 지방대사, 항산화 및 면역능에 미치는 효과)

  • Kwon, Sang-Hee;Woo, Hee-Jong;Han, Dae-Seok;Kim, Mi-Kyung
    • Journal of Nutrition and Health
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    • v.34 no.3
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    • pp.271-284
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    • 2001
  • This study was performed to investigate the effects of dried powders and water extracts of Paecilomyces tenuipes(P. tenuipes) and Cordyceps militaris(C. militaris) on lipid metabolism, lipid peroxidation and antioxidative capacity and immune status in rats. Thirty-five male Sprague-Dawley rats weighting 195$\pm$21g were grouped into five according to body weight. Ratw were raised for four weeks with diet containing either 4%, 2%(w/w) of dried P. tenuipes powders(TP-4, TP-2) or water extracts from equal amounts of each 4% P. tenuipes and C. militaris powder(TE-4, ME-4). Food intake, weight gain of all groups were not significantly different from those of control group. Lipid metabolism in general was not significantly different among all the groups. However both dried P. tenuipes powder lowered plasma cholesterol level slightly, water extract groups showed tendency of higher plasma HDL-cholesterol and lower liver cholesterol levels than control. Plasma and liver thiobarbituric acid reactive substance(TBARS) concentrations of all the experimental groups were lower than control group. Red blood cell(RBC) and liver superoxide dismutase(SOD) activities were not generally different among all groups. Liver xanthine oxidase(XOD) activities of all groups were tended to be lower than control group. Proliferation of aplenocytes induced by mitogens, concanavalin A and lipopolysaccharide, were increased in TP-2 group. The TP-4 group showed increased CD8 T cells and MHC class II expression without changes in CD4 T cells, B cells and G/M ratio, suggesting activated cytotoxic T cell activity in vivo. Increase of G/M ratio but not of MHC class II in TP-2 group indicated the possible acute inflammatory reaction by the ingested substances in gastrointestinal tract. ME-4 group showed enhanced cellular immunity without vigorous changes of immune parameters in brief periods. In conclusion, both P. tenuipes and C. militaris stimulated antioxidant capacity and immune status in rats. Among groups, water extract of C. militaris was most effective in both capacities, though dried powder of P. tenuipes at 2% dietary level was more effective in antioxidant activity, as various results by different strains were observed.(Korean J Nutrition 34(3) : 271~284, 2001)

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Functional Analysis of B7-H3 in Colonic Carcinoma Cells

  • Lu, Peng;Liu, Rong;Ma, Er-Min;Yang, Tie-Jian;Liu, Jia-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3899-3903
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    • 2012
  • B7-H3 is a newly discovered member of the B7/CD28 superfamily which functions as an important T-cell immune molecule. It has been reported recently that B7-H3 is highly expressed in many cancer cells, the data indicating that it may be a regulation factor contributing to tumor-resistance. In our study, we used bioinformatics to identify differentially expressed genes between colonic cancer cells and normal colonic cells, aiming to analyze mechanisms and identify sub-pathways closely related to progression, with the final aim of finding small molecule drugs which might interfere this progression. We found that ajmaline is one related factor which may enhance self-immunity in colon carcinoma therapy and B7-H3 plays important roles with regard to immunoreactions of colonic cancer cells. All the results indicate that H7-B3 is a favorable prognostic biomarker for colon carcinomas, providing novel information regarding likely targets for intervention.

Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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