• Natural Product Sciences
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• 제17권4호
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• pp.354-362
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• 2011

Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by abnormalities in T cell immunoregulation and hyperreactivity of B cells, leading to autoantibody production and multiorgan injuries. We investigated the effect of baicalin on aberrant immunoregulation in pristane-induced lupus mice. Mice received i.p. a single injection of 0.5 ml of pristane or PBS, and approximately 3 months later, were used as a pristane-induced lupus model or healthy controls. The pristane-induced lupus mice and healthy mice were randomly divided into three groups: healthy mouse group (healthy control), pristane-primed lupus control group (lupus control), and baicalin (BAC)-treated pristane-primed lupus mouse group (BAC-treated lupus). The pristane-induced lupus mice and healthy mice were administrated orally with BAC 50 mg/kg or PBS once in a day for 10 ds. These results demonstrated that levels of serum IL-6, LPS-induced production of IL-6, $PGE_2$ and NO by macrophages, $PGE_2$-stimulated production of IL-6 by macrophages and IFN-${\gamma}$ by thymocytes, and an overexpression of splenic NKT cells and CD69+CD4+ T cells were downregulated in BAC-treated lupus compared to lupus control, while reduced apoptosis of splenic CD4+ T cells were upregulated. Therefore, these findings suggest that BAC may attenuate autoimmunity and disease activity in lupus via downregulation of aberrant activation of T cells and inhibition of overproduction of IL-6 and $PGE_2$ in pristane-induced lupus mice.

• IMMUNE NETWORK
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• 제9권2호
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• pp.58-63
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• 2009

Background: T cell immunoglobulin and mucin domain containing 3 protein (Tim-3) expressed on terminally differentiated Th1 cells plays a suppressive role in Th1-mediated immune responses. Recently, it has been shown that N-glycosylation affects the binding activity of the Tim-3-Ig fusion protein to its ligand, galectin-9, but the binding properties of non-glycosylated Tim-3 on $CD4^+CD25^+$T cells has not been fully examined. In this study, we produced recombinant Tim-3-Ig fusion proteins in different cellular sources and its N-glycosylation mutant forms to evaluate their binding activities to $CD4^+CD25^+$T cells. Methods: We isolated and cloned Tim-3 cDNA from BALB/C mouse splenocytes. Then, we constructed a mammalian expression vector and a prokaryotic expression vector for the Tim-3-Ig fusion protein. Using a site directed mutagenesis method, plasmid vectors for Tim-3-Ig N-glycosylation mutant expression were produced. The recombinant protein was purified by protein A sepharose column chromatography. The binding activity of Tim-3-Ig fusion protein to $CD4^+CD25^+$T cells was analyzed using flow cytometry. Results: We found that the nonglycosylated Tim-3-Ig fusion proteins expressed in bacteria bound to $CD4^+CD25^+$T cells similarly to the glycosylated Tim-3-Ig protein produced in CHO cells. Further, three N-glycosylation mutant forms (N53Q, N100Q, N53/100Q) of Tim-3-Ig showed similar binding activities to those of wild type glycosylated Tim-3-Ig. Conclusion: Our results suggest that N-glycosylation of Tim-3 may not affect its binding activity to ligands expressed on $CD4^+CD25^+$T cells.

• Korean Journal of Acupuncture
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• 제21권3호
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• pp.105-120
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• 2004

Objective : The aim of this study was to investigate the effect of Mori Folium herbal acupuncture at St36 on ovalbumin-induced asthma in mice. Methods : C57BL/6 mice were sensitized and challenged with OVA (ovalbumin) for 12 weeks (once a week) Two experimental groups were treated with different concentrations (1%, 0.1%) of Mori Folium herbal acupuncture at Chok-samni (St36) for the later 8 weeks (3times/week). Result : 1. Lung weight of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 4. The number of $Gr-1^+/CD11b,\;CCR3^+,\;CD4^+,\;CD8^+,\;CD3e^+/CD69^+,\;IgE^+/B220^+$ cells in the lungs of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 5. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 6. The concentration of IL-4 in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. Conclusion : We conclude that Mori Folium herbal acupuncture is effective on OVA-induced asthma of C57BL/6 mouse.

• IMMUNE NETWORK
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• 제20권6호
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• pp.51.1-51.17
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• 2020

Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

• IMMUNE NETWORK
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• 제16권1호
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• pp.13-25
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• 2016

Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4⁺ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bone-marrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4⁺ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4⁺ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4⁺ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3^- regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3⁺ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.62-64
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• 2008

A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

• 동의생리병리학회지
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• 제20권4호
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• pp.896-901
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• 2006

Zingiberis rhizoma(ZB) has been used to treat a various condition and disease in traditional oriental medicine. The present study was conducted to evaluate the immunomodulatory effect of aqueous-extracted ZB(ZBE) on methotrexate (MTX)-induced immune suppression in mouse spleen cells. In spleen cell proliferation assay, ZBE enhanced mitogenic activity in mouse spleen cells. In RT-PCR, ZBE induced IL-2, IFNr and IL-6 cytokine gene expression in mouse spleen cells. In spite of MTX treatment, IL-2, IFNr and IL-6 gene expressions sustained in MTX treated spleen cells. CD45R/B220, pan B marker was slightly increased in ZBE treated mouse spleen cells. IL-6, B cell tropical cytokine, production was induced by ZBE-treated mouse spleen cells and IL-6 production was sustained on MTX-ZBE co-cultured cells. ZBE administration enhanced suNival of S-180 bearing mouse. These data indicate that ZBE has a protective effect of immune suppression caused by MTX, and ZBE may be enhance cellular and humoral function by regulate cytokine gene expression as well as the mitogenic effect on spleen cells.

• 대한의생명과학회지
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• 제2권2호
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• pp.275-282
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• 1996

저자들은 마우스를 실험모델로 하여 간흡충의 항원을 투여 했을 때 비장조직에 대한 CD3, CD4 및 CD8 모노클로날 항체의 반응 여부를 알아보고자 하였다. 즉, 간흡충에 대한 세포면역학적인 특성을 규명고자 하였으며 특히 비장 조직에 대한 phenotype을 관찰한 결과 다음과 같은 결과를 얻었다. 간흡충의 조항원을 면역증강제와 함께 복강 투여한 다음 일정 기간 후에 비장조직을 Avidin-biotin complex 면역조직염색을 실시한 결과 CD3에서 강한 양성 반응을 나타냈고 CD4와 CD8에서는 약한 반응을 나타냈다. 조직부위를 보면 피막, 혈관, 임파관, 백수부위와 림프구 및 대식 세포의 세포막에서 양성반응을 보였다.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• Korean Journal of Acupuncture
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• 제20권3호
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• pp.101-114
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• 2003

To study the effects of anti-cancer, anti-metastasis and immune response improvement of herbal-acupuncture with Aucklandiae Radix diffusae herba infusion solution(AKL-HAS), we injected AKL-HAS into Zusanli(St36) of C57BL/6 mice implanted intravenously with B16-F10 melanoma. The results were obtained as follows : 1. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the spleen cell proliferation in Balb/c mouse was significantly increased compared with that of the control group. 2. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the percentage of $CD25^{+}/CD4^{+},\;CD8^{+}/CD3e^{+},\;CD69^{+}/B220^{+},\;NK1.1^{+}/CD3e^{+}$ cells in C57BL/6 mouse PBMCs was increased compared with that of the control group. 3. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the pulmonary colony number of C57BL/6 mice implanted intravenously with B16-F10 melanoma was decreased significantly compared with that of the control group. 4. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, MST(Median Survial Time) and ILS(Increase of Life Span) of C57BL/6 mice implanted intravenously with B16-F10 melanoma were increased significantly compared with those of the control group.