• Korean Journal of Microbiology
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• v.47 no.4
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• pp.342-347
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• 2011

T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

• BMB Reports
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• v.48 no.2
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• pp.103-108
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• 2015

Trichomoniasis caused by the parasitic protozoan Trichomonas vaginalis is the most common sexually transmitted disease in the world. Dendritic cells are antigen presenting cells that initiate immune responses by directing the activation and differentiation of naive T cells. In this study, we analyzed the effect of Trichomonas vaginalis-derived Secretory Products on the differentiation and function of dendritic cells. Differentiation of bone marrow-derived dendritic cells in the presence of T. vaginalis-derived Secretory Products resulted in inhibition of lipopolysaccharide-induced maturation of dendritic cells, down-regulation of IL-12, and up-regulation of IL-10. The protein components of T. vaginalis-derived Secretory Products were shown to be responsible for altered function of bone marrow-derived dendritic cells. Chromatin immunoprecipitation assay demonstrated that IL-12 expression was regulated at the chromatin level in T. vaginalis-derived Secretory Products-treated dendritic cells. Our results demonstrated that T. vaginalis- derived Secretory Products modulate the maturation and cytokine production of dendritic cells leading to immune tolerance.

• IMMUNE NETWORK
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• v.10 no.2
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• pp.46-54
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• 2010

Background: Graft-versus-host disease (GVHD) is initiated when alloreactive donor T cells are primed by host APCs to undergo clonal expansion and maturation. Since there is a controversy regarding the role of nonhematopoietic cells in GVHD, we wanted to investigate the influence of MHC disparity on nonhematopoietic cells on the pathogenesis of GVHD in the MHC-haplomismatched C57BL/6 ($H-2^b$) or DBA/2 $(H-2^b){\rightarrow}$unirradiated ($C57BL/6{\times}DBA/2$) $F_1(BDF_1;\;H-2^{b/d})$ murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD). Methods: We generated ($BDF_1{\rightarrow}C57BL/6$), ($BDF_1{\rightarrow}DBA/2$), and ($BDF1{\rightarrow}BDF_1$) chimeras and examined GVHD-related parameters and donor cell engraftment in those chimeras. Results: Using this experimental system, we found that 1) severe aGVHD across MHC Ag barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloAgs for maximal GVHD manifestations; 2) host APCs were sufficient to break B cell tolerance to self molecules in cGVHD, whereas host APCs were insufficient to induce autoimmunity in aGVHD; 3) donor cell engraftment was greatly enhanced in the host with MHC-matched nonhematopoietic cells. Conclusion: Taken together, our results provide an insight into how MHC disparity on GVHD target organs contribute to the pathogenesis of GVHD.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.46 no.4
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• pp.399-406
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• 2013

Our aim was to determine the effects of a citrus by-product (CBP) and CBP fermented by Lactobacillus plantarum (LP-CBP), provided as dietary supplements, on the growth performance, feed utilization, innate immunity and temperature tolerance of red seabream. A diet without inclusion of CBP or LP-CBP was used as a control and four other experimental diets were formulated to replace wheat flour by 4% and 8% of either CBP or LP-CBP (designated as Con, LP-CBP4%, LP-CBP8%, CBP4% and CBP8%, respectively). Experimental diets were fed to triplicate groups of 25 fish (initial body weight, 55.0 g) for 9 weeks. Growth performance and feed utilization were not significantly different among all the groups. Bone collagen content was significantly increased by supplementation with CBP and LP-CBP. Vitamin C concentration tended to be higher in livers of fish fed the supplements than in the control group. Myeloperoxidase, lysozyme and superoxide dismutase activities were higher in fish fed CBP or LP-CBP than in fish fed the control diet. When fish were exposed to low water temperature, cumulative mortalities of those fed CBP or LP-CBP supplemented diets were lower (29%, 33%, 34% and 33% mortalities for LP-CBP4%, LP-CBP8%, CBP4% and CBP8%, respectively) than in the control group (58%). Therefore, inclusion of either CBP or LP-CBP at up to 8% in red seabream diet brings benefits through enhanced innate immunity and better tolerance of low water temperature.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.229-236
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• 2004

Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma, small cell lung carcinoma and neuroblastoma. Immunity against GD2 has anti-tumor activities, but GD2 is poorly immunogenic. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In our previous study, we produced anti-idiotypic antibodies mimicking GD2 (3A4 and 3H9), which induced humoral immunity. However, cellular immunity is essential to eradicate tumor cells in vivo as well as humoral immunity. In the present study, we investigated whether these anti-idiotypic antibodies 3A4 and 3H9 could induce cellular immunes responses. Methods: BALB/C mice were immunized with anti-idiotypic antibody 3A4 or 3H9, or normal mouse IgG as a negative control. Lymphoproliferative responses, cytokine production responses, and delayed-type hypersensitivity reactions were measured in mice immunized with the anti-idiotypic antibodies. Results: Both the anti-idiotypic antibody 3A4 and 3H9 induced GD2-specific lymphoproliferative responses and $IFN-{\gamma}$ production of lymph node lymphocytes in BALB/C mice. Only anti-idiotypic antibody 3H9 induced significant GD2-specific delayed-type hypersensitivity in the mice. Conclusion: These results show that anti-idiotypic antibodies 3A4 and 3H9 have the potentiality of inducing GD2-specific cellular immune responses that cannot be induced by the native antigen GD2 itself.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.174-180
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• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• IMMUNE NETWORK
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• v.5 no.3
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• pp.150-156
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• 2005

Background: Dendritic cells (DCs) playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of antigen presenting cell (APC) function of DCs, we searched for and characterized APC function modulators from natural products. Methods: DCs were cultured in the presence of propolis components, WP and CP, and then examined for their ability to present exogenous antigen in association with major histocompatibility complexes (MHC). Results: WP and CP inhibited class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells, and DCs generated from bone marrow cells with GM-CSF and IL-4. The inhibitory activity of WP and CP appeared to be due not only to inhibition of phagocytic activity of DCs, but also to suppression of expression of MHC molecules on DCs. We also examined the effects of WP and CP on T cells. Interestingly, WP and CP increased IL-2 production from T cells. Conclusion: These results demonstrate that WP and CP inhibit MHC-restricted presentation of exogenous antigen through down-regulation of phagocytic activity and suppression of expression of MHC molecules on DCs.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.10
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• pp.1477-1482
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• 2001

Research in low cost feeds with high nutritional value and immunogenicity is important to reduce production cost and increase yields in the shrimp industry. In this study, immunostimulants of bacterial origin (peptidoglycan and lipopolysaccharides) and egg white were incorporated in shrimp diets as feed additives to determine the growth, survival and tolerance of Penaeus monodon to white spot syndrome virus (WSSV). Although the results obtained were not statistically significant (p>0.05) among the treatments, shrimp fed with bacterial additives and egg white showed higher weight gain, specific growth rate and survival than those fed on commercial shrimp diet. Shrimp fed with artificial diet showed 100% mortality when challenged with WSSV. However, shrimp fed on peptidoglycan supplemented diet had higher survival than their counterpart, whereas shrimp fed on egg white supplemented diet had a higher specific growth rate and better tolerance when challenged with WSSV. Further studies are required to determine the effectiveness and optimization of bacterial strains and egg white as feed additives to increase production and enhance the shrimp immune response to diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2665-2669
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• 2015

CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and $TNF-{\alpha}$ secretion by DCs.

• Preventive Nutrition and Food Science
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• v.16 no.1
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• pp.37-44
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• 2011

The potential probiotic of a total of 15 Bacillus species isolated from Korean soybean paste (doenjang) was evaluated. Among those tested, the CSY191 and CSY388 strains were selected as probiotic bacteria due to their acid and bile tolerance, respectively. These strains were classified as Bacillus subtilis based on morphological, physiological, and chemotaxonomic features as well as on phylogenetic analysis based on their 16S rDNA sequences. These strains CSY191 and CSY388 showed a significant survival with rate range of 30.0 to 58.3% and of 31.0% to 58.1%, respectively, under artificial gastric acidic conditions at pH 3.0. These CSY191 and CSY388 strains appeared to have high antimicrobial activity against Salmonella Typhimurium, Bacillus cereus and Listeria monocytogenes. Also, methanol extractions (surfactin-like compounds) of strain CSY191 and strain CSY388 activated RAW264.7 microphages and induced the production of nitric oxide (NO) in a concentration-dependent manner, respectively. Therefore, strain CSY191 and strain CSY388 can be used as potential probiotics.