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        CD43 Expression Regulated by IL-12 Signaling Is Associated with Survival of CD8 T Cells

        Lee, Jee-Boong,Chang, Jun The Korean Association of Immunobiologists 2010 Immune Network Vol.10 No.5

        Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

      • Phenotypic changes induced by IL-12 priming regulate effector and memory CD8 T cell differentiation

        Lee, Jee-Boong,Lee, Kyoo-A,Chang, Jun 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18

        In addition to TCR and co-stimulatory signals, inflammatory cytokines such as IL-12 provide important signals for differentiation and survival of activated CD8 T cells, In the present study, to investigate the mechanisms by which IL-12 priming contributes to activation and enhanced survival of CD8 T cells, we searched the differentially regulated genes and markers by IL-12 during antigenic stimulation. Here, we show that IL-12 priming results in the increased subpopulation of CD127^(hi) cells, which differentiates into long-lived memory cells. We also found that IL-12 priming induces IL-10 expression from activated CD8 T cells, which is distinct from CD127 up-regulation. Direct IL-10 priming of CD8 T cells results in the significant increase of effector and memory CD8 T cell population after adoptive transfer, and this priming effect is closely associated with less susceptibility to apoptosis. Although IL-10 is known as a cytokine with anti-inflammatory and immunosuppressive properties, our results have shown that IL-10 has a direct and positive effect on the survival of CD8 T cells, together, we suggest that IL-10-dependent and independent effects of IL-12 play important roles in regulating differentiation and survival of activated CD8 T cells into effector and memory cells.

      • SCOPUSSCIEKCI등재

        천추에 발생한 원발성 경막상 유잉씨 육종 1례

        고창현,이지웅,안용붕,김병준,이상걸 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.2

        Recently we experienced a soft tissue sarcoma originated in the spinal epidural space at upper sacral area and extending into intrapelvic area in a young male patient. It was diagnosed primary Ewing's sarcoma histologically. Ewing's sarcoma is usually found in long bones. But rarely discovered in an extraosseous area. So spinal epidural Ewing's sarcoma is rare to be found. Only 6 cases were reported in the English literature until 1986. We present the case with review of literatures.

      • Intranasal Delivery of Cholera Toxin Induces Th 17- Dominated T-Cell Response to Bystander Antigens

        Chang, Jun,Lee, Jee Boong,Jang, Ji Eun,Song, Man Ki 이화여자대학교 약학연구소 2010 藥學硏究論文集 Vol.- No.20

        Cholera toxin (CT) is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that a promotes T helper type 2 (Th2) response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of a adjuvanticity to demarcate Thelper responses.

      • Vaccination with recombinant adenoviruses and dendritic cells expressing prostate-specific antigens is effective in eliciting CTL and suppresses tumor growth in the experimental prostate cancer

        Kim, Sol,Lee, Jee-Boong,Lee, Geon Kook,Chang, Jun Wiley Subscription Services, Inc., A Wiley Company 2009 The Prostate Vol.69 No.9

        <B>BACKGROUND</B><P>Prostate cancer is currently the most commonly diagnosed cancer in men and the second leading cause of cancer-related death in men in the US. Immunological approaches may provide an alternative option for prevention and treatment of prostate cancer.</P><B>METHODS</B><P>To develop vaccine against prostate cancer using mouse model, we constructed three recombinant adenoviruses expressing prostate-specific membrane antigen (rAd/PSMA), prostate stem cell antigen (rAd/PSCA) and six-transmembrane epithelial antigen of the prostate (rAd/STEAP), that were specifically up-regulated in the transgenic murine prostate cancer.</P><B>RESULTS</B><P>Male C57BL/6 mice were immunized by intravenous injection of these recombinant adenoviruses and subsequently by subcutaneous injection of dendritic cells pulsed with TRAMP-C1 tumor lysate. After subcutaneous challenge with TRAMP-C1 cells, tumor growth was significantly delayed in the immunized mice compared to the control group. Surprisingly, significant numbers of STEAP-specific CD8 T cells were detected in the peripheral blood and the spleen of immune mice using MHC I tetramers, and injection of rAd/STEAP alone followed by pulsed DC was sufficient to inhibit tumor growth. Therapeutic vaccination also significantly delayed the growth of pre-established tumors.</P><B>CONCLUSION</B><P>Our results suggest that STEAP is a good immunologic target antigen against prostate cancer and our vaccination regimen successfully elicits anti-tumor CTL responses and suppresses tumor growth. More studies will expedite the development of this vaccine toward clinical application. Prostate 69: 938–948, 2009. © 2009 Wiley-Liss, Inc.</P>

      • Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection

        Yu, Jae-Rang,Kim, Sol,Lee, Jee-Boong,Chang, Jun 이화여자대학교 약학연구소 2009 藥學硏究論文集 Vol.- No.19

        Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses. Here, a recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein (amino acids 130 to 230) engineered by codon optimization and tandem repetition for higher-level expression, was constructed and evaluated for its potential as an RSV vaccine in a murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal immunoglobulin A responses were also induced by a single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither gamma interferon- nor interleukin-4-producing CD4 T cells directed to I-E^(d)-restricted epitope were detected in the lungs of rAd/3xG-immune mice upon challenge, whereas priming with vaccinia virus expressing RSV G (vvG) elicited strong Th1/Th2 mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in the rAd/3xG-immune group than in the vvG-primed group. Together, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a promising vaccine regimen against RSV infection.

      • Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection

        Yu, Jae-Rang,Kim, Sol,Lee, Jee-Boong,Chang, Jun 이화여자대학교 세포신호전달연구센터 2008 고사리 세포신호전달 심포지움 Vol. No.10

        Respiratory syncytial virus(RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses. Here, a recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein(amino acids 130 to 230) engineered by codon optimization and tandem repetition for higher level expression, was constructed and evaluated for its potential as an RSV vaccine in murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal IgA responses were also induced by single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither IFN-γ nor IL-4-producing CD4 T cells directed to I-E^(d)-restricted epitope were detected in the lungs of rAd/3xG-immune mice upon challenge, whereas vvG priming elicited strong Th1/Th2-mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in rAd/3xG-immune group than vvG-primed group. Together, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a promising vaccine regimen against RSV infection.

      • Evaluation of Protective Efficacy of Respiratory Syncytial Virus Vaccine against A and B Subgroup Human Isolates

        Jun, Chang,Ji-Eun, Jang,Jee-Boong, Lee,Kyung-Hyo, Kim,Sung Moo, Park,Byoung-Shik, Shim,In Soo, Cheon,Man Ki, Song 梨花女子大學校 藥學硏究所 2012 藥學硏究論文集 Vol.- No.22

        Human respiratory syncytial virus (HRSV) is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. HRSV is divided into two subgroups, HRSV-A and HRSV-B, based on sequence variation within the G gene. Despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for HRSV. In this study, we have detected and identified the HRSV by RT-PCR from nasopharyngeal aspirates of Korean pediatric patients. Interestingly, all HRSV-8 isolates exhibited unique deletion of 6 nucleotides and duplication of 60 nucleotides in the G gene. We successfully amplified two isolates ('KR/A/09-8' belonging to HRSV-A and 'KR/B/10-12' to HRSV-B) on largescale, and evaluated the cross-protective efficacy of our recombinant adenovirus-based HRSV vaccine candidate, rAd/3xG, by challenging the immunized mice with these isolates. The single intranasal immunization with rAd/3xG protected the mice completely from KR/A/09-8 infection and partially from KR/B/1D-12 infection. Our study contributes to the understanding of the genetic characteristics and distribution of subgroups in the seasonal HRSV epidemics in Korea and, for the first time, to the evaluation of the cross-protective efficacy of RSV vaccine against HRSV-A and -B field-isolates.

      • SCOPUSSCIEKCI등재

        당뇨병이 동반된 뇌졸중환자에 있어서의 임상적 고찰

        고창현,구영환,김형기,이지웅,안용붕,김병준,김응진 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.5

        The authors analyzed 72 cerebral stroke with diabetes mellitus who admitted to our hospital during 1989 to 1993. Pathophysiology and clinical characteristic complication and mortality was analyzed. Following are results : 1) Among 398 total cerebral stroke who were hospitalized to our hospital during 1989 to 1993. there were 72 cerebral stroke with diabetes(18%). 2) The rate of cerebral infarction and hemorrhage was 67% and 33%. The infarction rate was much higher compared with it of general cerebral stroke. 3) Various complications were presented and mortality rate was 24.2% which was regarded higher than it of general cerebral stroke. 4) Association of mortality. prognostic index and other variables were analyzed.

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