• The Journal of Korean Medicine
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• v.24 no.3
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• pp.1-10
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• 2003

Background : Asthma is a chronic inflammatory disorder under immunological influence. Gamichunggumgangwha-tang (CG, Jiaweiqingjinjianghuo-tang) and Gamiyukmigiwhang-tang (YM, Jiaweiliuweidihuang-tang) are herbal tonics for asthma from traditional herbal medicine. Objective : To evaluate the effect of CG and YM on immune cell & serum OA-specific IgE in broncho-alveolar lavage fluid (BALF) in a rat asthma model. Materials and Methods : Rats were sensitized with OA; at day I sensitized group and CG and YM groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml. At the same time, 1 ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by Lp. 14 days after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BALF was collected from the rats. Rats were orally administered with each of CG and YM extract for 14 days since the day after local immunization. Lymphocyte, CD4＋ T cell and CD8＋ T cell counts, CD4＋/CD8＋ ratio in BALF, change of serum OA-specific IgE level, CD4＋ T cell and CD8＋ T cell percentages in the peripheral blood were measured and evaluated. Results : CG and YM showed an alleviating effect on asthmatic responses of rats. CG decreased total cell, lymphocyte, CD4＋ T cells in BALF, and serum OA-specific IgE level as compared with the control group. YM decreased lymphocytes as compared with the control group. CD4＋/CD8＋ ratio in BALF from the CG and YM groups and serum OA-specific IgE level from the YM group didn't show any significant variation from the control group. Conclusion : CG alleviated asthmatic hyperreactivity of the immune system through CD4＋ T cells and serum IgE. Further the study of this immune system modulating mechanism is expected.

• The Journal of Korean Society of Virology
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• v.27 no.1
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• pp.97-104
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• 1997

For 16 years after the finding of HIV as an agent of AIDS in 1981, HIV therapeutic drugs of reverse transcriptase inhibitors (AZT, ddI, ddC, d4T) and protease inhibitors have been developed. Recent studies also were focused on a combination therapy by using HIV therapeutic drugs or natural compounds. Korean red ginseng (KRG) of natural compounds has been well known as a good reinforcement agent in Asia. The percentage of CD3+CD4+ T cell in nine HIV-infected patients without KRG treatment averaged 17.8% on baseline and decreased 15.8% after 6 months, whereas the percentage of the cell in fifteen HIV-infected patients with KRG treatment averaged 15.3% on baseline and increased up to 18.9% after the same period. The average percentage of CD3+CD8+ T cell of KRG-nontreated and KRG-treated HIV patients increased after 6 months 47.8% to 50.7% and 44.7% to 51.4%, respectively; and the average percentage of B and NK cell in the KRG-nontreated and KRG-treated HIV patients decreased 9.4% to 7.9% and 13.0% to 9.7%, 8.9% to 8.5% and 16.2% to 11.6%, respectively. KRG, therefore, didn't have any effects on the CD3+CD8+ T cell, B cell, and NK cell. However, it seems that KRG has a potential activity for stimulatiing the CD3+CD4+ T cell and some inhibition on destroying of this cell with no significance.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.4
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• pp.597-606
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• 2008

Resorption of alveolar bone in periodontitis is due to excessive differentiation and activation of osteoclasts. Bacterial antigens causing periodontitis activates CD4 T cells, which leads to expressing RANK ligand (RANKL) on CD4 T cells. RANKL binds RANK on preosteoclasts or osteoclasts, and enhances the differentiation preosteoclasts into osteoclasts and the activation of mature osteoclasts. CD137, one of TNF receptor (TNFR) family, expressed on activated T cells binds with CD137 ligand (CD137L) on antigen presenting cells. Cross-linking of CD137 by CD137L acts as T cell co-stimulatory signals and, therefore, enhances the activation of T cell. In this study, I elucidated the biological responses of CD137L on (pre)osteoclasts and RANKL on T cells in the context of in vivo interaction between T cells and osteoclasts. RAW264.7, murine monocytic cells, constitutively express CD137L. Ligation of CD137L with anti-CD137L mAb inhibited RANKL-induced osteoclast formation in a dosedependent manner. Bone marrow cells are expressed CD137L by the treatment with M-CSF. Cross-linking of CD137L abolished M-CSF/ RANKL-evoked the formation of multi-nucleated osteoclasts. Both mouse CD4 and CD8 T cells are expressed RANKL following their activation. Ligation of RANKL with OPG, the decoy receptor for RANKL, inhibited both CD4 and CD8 T cell proliferation. These effects were attributed to RANKL-induced apoptosis. These data indicate that CD137L and RANKL on osteoclasts and T cells, respectively provide them with inhibitory signal.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.155-158
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• 2023

In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4⁺ CD8⁺T cell, CD3^-CD172^-CD8⁺ NK cell and CD172⁺ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immuneenhancing effects by increasing the roles of T cells and NK cell in porcine.

• Molecules and Cells
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• v.28 no.2
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• pp.125-130
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• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.268-280
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• 2011

Background: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). Methods: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-${\gamma}$ staining. Results: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. Conclusion: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein-specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.

• Korean Journal of Poultry Science
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• v.28 no.3
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• pp.231-237
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• 2001

To examine the effects of feed additives on the expression of perpheral blood cell surface molecules, phagocytosis and antigen specific antibody formation, broilers were randomly assigned to $T_{1}$ , $T_{2}$ , $T_{3}$ , and $T_{4}$ groups. $T_{1}$ group was fed diet without any additives for 13 weeks, $T_{2}$ was fed diet with full fat flax, $T_{3}$ was fed diet with full fat flax containing $\alpha$-tocopherol, and $T_{4}$ was fed diet with full- fat flax containing $\alpha$-tocopherol and selenium. Since 5 weeks feeding the data were examined by flow cytometry using a panel of monoclonal antibodies. The expression of monocyte in all treated groups was significantly increased, in which the ratio of expression in $T_{3}$ group was especially evident. B cell expression of all treated groups was increased more than 2 fold. The expression of CD4+(helper T cell) cell and CD8+(cytotox$ic^pressor T cell) cell of all treated groups also was increased.ed.

• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Molecules and Cells
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• v.42 no.3
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• pp.228-236
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• 2019

CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

• Molecules and Cells
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• v.26 no.1
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• pp.67-73
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• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.