• Journal of Pharmacopuncture
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• v.7 no.3
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• pp.27-35
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• 2004

Beevenom immunotherapy(BVIT) in allergic patients is a well-established treatment modality for the prevention of systemic anaphylactic reactions caused by insect stings. BVIT is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Inhibition of T cells after BVIT also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL-10, also associated with the inhibited status of T cells after BVIT. Suppression of T cells by IL-10 is an active process, which depends on the expression and participation of CD28. Immune tolerance in specific allergen immunotherapy might be a consequence of decreased Th2 or increased Th1 response of allergen specific T lymphocytes. BVIT shifted cytokine responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting direct effects on T cells. Many studies showed that severe side effects due to venom immunotherapy are rare. These results suggest that immunological changes after BVIT may be applied to be therapeutic alternative of general allergic diseases including beevenom allergy.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.143-148
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• 2002

The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, thus transcriptional regulation constitutes a major mechanism of glial tropism in PML. Here we found that pentanucleotide sequence immediately upstream of the TATA sequence functions as a cell-specific silencer in the JC virus transcription. In vitro binding studies showed that synthetic oligonucleotides spanning a pentanucleotide sequence, designated "oligo 2", interacts with nuclear proteins from non-glial cells in a cell-specific manner. Furthermore, the sequence preferentially repressed the heterologous thymidine kinase promoter activity in non-glial cells. We also tested whether JC virus transcription is controlled by DNA methylation. Transient transfection of in vitro methylated JC virus promoter abolished transcription in both the glial and non-glial cells. The repression fold was much larger in glial cells than in non-glial cells. Taken together, this finding suggests that glial cell-specific expression of the JC virus is controlled by DNA methylation as well as cell-specific silencers.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.82-83
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• 2003

In the past it was thought that autoimmunity is mediated by antibodies and immune complexes. It has now become clear that many diseases, especially tissue specific, are T cell mediated or at least T cell dependent. The pathogenesis of cell-mediated autoimmune diseases, such as multiple sclerosis, uveitis, diabetes, arthritis, and others, is thought to be in a large measure driven by interferon-gamma-producing antigen-specific T cells polarized toward the Th1 phenotype. (omitted)

• IMMUNE NETWORK
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• v.10 no.1
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• pp.1-4
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• 2010

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing $CD4^+$ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.

• Proceedings of the Microbiological Society of Korea Conference
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• 2008.05a
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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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.134-149
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• 2016

Objectives : Gal-Geun-Tang (GT) has been described from SANGHAN in Korean traditional medicine and known to act against cold, fever, hypertension, and nasal catarrh. However, little has yet been learned about the effect of GT on immune function. In the current study, in vitro and in vivo immunomodulatory activity of GT (water extract) was investigated.Methods : Water extract of GT induced in vitro proliferation of spleen cells and significantly increased their proliferative responses during anti-CD3 activation. Using purified splenic T and B cells, it was revealed that GT has a mitogenic activity to B cells and promotes their proliferation induced by lipopolysaccharide, whereas T cell proliferation was not triggered and GT was rather inhibitory to T cell activation caused by anti-CD3 antibody. In the presence of antigen presenting cells (APC), GT addition resulted in a significant increase of IFNγ and IL-4, but not IL-2, production. However, addition of high concentration (1,000㎍/㎖) of GT led to a marked reduction in T cell cytokine production and under such condition, GT facilitated apoptosis of T cells when examined by flow cytometry with propidium iodide staining.Results : In vivo immunomdulation of GT was also investigated using a mouse model. Following keyhole limpet hemocyanin (KLH) immunization, GT (1 ㎎/day) was orally administered for 9 days. Cell numbers in thymus, spleen and peripheral blood were not altered by GT administration, indicating that such dose is not immunotoxic. Cell numbers in draining lymph nodes (LN) and ex vivo Ag-specific proliferation of LN cells were significantly elevated by GT administration. However, any preferential stimulation of T or B and CD4⁺ or CD8⁺ T cell subpopulations was not observed in a flow cytometric analysis of LN cells. This result shows that GT does not promote in vivo B cell proliferation while GT enhances Ag-specific proliferation of LN cells, unlike what was observed in vitro.Conclusions : For a further understanding of in vivo immunomodulatory activity of GT, ex vivo cytokine production of LN cells obtained from KLH-immunized mice was evaluated. Ag-specific IFNγ production was significantly higher in GT-treated mice when compared to PBS-treated control mice. In contrast, IL-4 production in GT-treated group was comparable to control group unlike to in vitro data. In addition, GT administration did not result in any significant differences in serum levels of Ig (IgM, IgG1 and IgG2a) between GT-treated and control groups. Taken together, these data strongly support that GT promotes immune response, more profoundly type 1 helper T cell (Th1) activity and GT may be applicable for treatment of intracellular parasite infection such as viral diseases.

• Journal of Periodontal and Implant Science
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• v.32 no.4
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• pp.827-836
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• 2002

The present study was performed to evaluate how cellular and humoral immune responses were perturbed by immunization of mixed periodontal bacterial biofilms. Each group of mice was immunizared with 1) Poqhyromonas gingivalis (P. gingivaliis) grown as a planktonic culture, 2) Fusobacterium nucleatum (F. nucleatum), 3) P. gingivalis grown as a biofilm, or 4) mixed P. gingivalis plus F. nucleatum grown as a biofilm culture, respectively. Immune mouse sera were collected from each mouse. Spleens were harvested to isolate T cells and consequently stimulated with antigen presenting cells and P. gingivalis whole cell antigen to establish P. gingivalis-specific T cell lines. There were no significant differences in the mean anti- gingivalis IgG antibody titers among mouse groups. Immunization of mice with pure P. gingivalis biofilm or mixed P gingivalis plus F. nucleatum biofilm resulted in significant reduction o f antibody avidity and opsonophagocytois function. INF-$\gamma$production by P. gingivalis-specific T cell lines was also substantially recluced in mouse groups immunized with the biofilm. It was concluded that P. gingivalis biofilm perturbs the cellular and humoral immune responses in periodontal disease.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.233-241
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• 2016

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-K^b complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.264-274
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• 2013

The unrestricted population of $CD4^+Foxp3^+$ regulatory T (Treg) cells, which have been known to control the expression of autoimmune diseases and protective immunity to inflammatory reactions, has led to greater appreciation of functional plasticity. Detecting and/or isolating Ag-specific $CD4^+Foxp3^+$ Tregs at the single cell level are required to study their function and plasticity. In this study, we established and compared both MHC class II tetramer and intracellular CD154 staining, in order to detect $CD4^+Foxp3^+$ Treg specific for foreign Ag in acute and chronic infections with lymphocytic choriomeningitis virus (LCMV). Our results revealed that MHC class II tetramer staining showed a lower detection rate of LCMV $GP_{66-77}$-specific $CD4^+$ T cells because most of MHC class II tetramers were unbound and unstable when combined staining was performed with intracellular cytokines. In contrast, intracellular CD154 staining was revealed to be easier and simple for detecting LCMV $GP_{66-77}$-specific $CD4^+$ T cells, compared to MHC class II tetramer staining. Subsequently, we employed intracellular CD154 staining to detect LCMV $GP_{66-77}$-specific $CD4^+Foxp3^+$ Tregs using $Foxp3^{GFP}$ knock-in mouse, and found that LCMV $GP_{66-77}$-specific $CD4^+Foxp3^+$ Tregs and polyclonal $CD4^+Foxp3^+$ Tregs showed differential expansion in mice infected with LCMV Arms or Cl13 at acute (8 and 13 days pi) and chronic phases (35 days pi). Therefore, our results provide insight into the valuable use of intracellular CD154 staining to detect and characterize foreign Ag-specific $CD4^+Foxp3^+$ Treg in various models.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.41-48
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• 2002

Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.