• 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.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.10-17
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• 2011

Objective: To evaluate the immune-stimulatory potential of extracts of Broussonetia kazinoki Siebold (BK) on specific cellular and humoral immune responses in ovalbumin (OVA)-immunized mice. Material and Methods: C57BL/6 mice were immunized intraperitoneally with OVA/alum ($100{\mu}g/200{\mu}g$) on days 1, 8, and 15. BK (100, 300 or 1000 mg/kg) was given to mice orally for 21 days (from day 1 to day 21). At day 22, OVA-, lipopolysaccharide (LPS)- and concanavalin A (Con A)-stimulated splenocyte proliferation and OVA-specific and total antibodies were measured in plasma. Further, the effects of BK on expression of cytokine mRNA in OVA-immunized mice splenocytes were evaluated by RT-PCR analysis. Results: BK significantly enhanced OVA-, LPS-, and Con A-induced splenocyte proliferation in OVA-immunized mice (p<0.01). BK also significantly enhanced total IgM and OVA-specific IgG1 levels in plasma compared with the OVA control group. Moreover, BK up-regulated significantly the expression of mRNA level of IL-2 and IFN-${\gamma}$ in splenocytes. Conclusions: BK has immune-stimulating activity in an OVA-immunized mouse model system, enhancing the Th1 immune response. BK showed no cytotoxicity in this system, suggesting that BK may be a safe and effective adjuvant in humans.

• The Korean Journal of Food And Nutrition
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• v.26 no.3
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• pp.375-382
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• 2013

The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at $100^{\circ}C$(OeE-100). OeE-100 doses up to $62.5{\mu}g/m{\ell}$ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous ($4{\sim}100{\mu}g/mouse$) or oral (2 mg/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-${\alpha}$, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 ($10{\sim}100{\mu}g/mouse$) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 ($100{\mu}g/mouse$) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-${\gamma}$. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.

• Journal of Pharmacopuncture
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• v.20 no.2
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• pp.107-111
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• 2017

Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran. Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups. Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and $IFN-{\gamma}$ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity. Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.1-7
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• 2003

Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.303-308
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• 2011

This study investigated whether elevated host immune capacity can inhibit T. gondii infection. For this purpose, we used silk protein extracted from Bombyx mori cocoons as a natural supplement to augment immune capacity. After silk protein administration to BALB/c mice for 6 weeks, ratios of T lymphocytes ($CD4^+$ and $CD8^+$ T-cells) and splenocyte proliferative capacities in response to Con A or T. gondii lysate antigen (TLA) were increased. Of various cytokines, which regulate immune systems, Th1 cytokines, such as IFN-${\gamma}$, IL-2, and IL-12, were obviously increased in splenocyte primary cell cultures. Furthermore, the survival of T. gondii (RH strain)-infected mice increased from 2 days to 5 or more days. In a state of immunosuppression induced by methylprednisolone acetate, silk protein-administered mice were resistant to reduction in T-lymphocyte ($CD4^+$ and $CD8^+$ T-cells) numbers and the splenocyte proliferative capacity induced by Con A or TLA with a statistical significance. Taken together, our results suggest that silk protein augments immune capacity in mice and the increased cellular immunity by silk protein administration increases host protection against acute T. gondii infection.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.776-784
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• 2014

Tuna cooking juice concentrate (TCJC) is by-produced during the canning processing of skipjack tuna Katsuwonus pelamis and it is well known that TCJC contains various nutritional components. Therefore, the immuno-stimulating activity of TCJC was investigated using macrophage RAW 264.7 cell line and the spleen cell isolated from BALB/c mice. The TCJC increased the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ in a dose-dependent manner compared to the control in RAW 264.7 cells without any toxicity. In particular, the production of TNF-${\alpha}$ was increased over 300-fold. The production of both Th1 cytokine (such as IFN-${\gamma}$, TNF-${\alpha}$, IL-2, and IL-12) and Th2 cytokine (IL-4, IL-6, IL-10) was also increased by TCJC treatment in splenocytes. Moreover, the TCJC increased the splenocyte proliferation in a concentration-dependent manner compared to control. These results indicate that TCJC may enhance immune function by promoting various cytokine production.

• The Journal of Pediatrics of Korean Medicine
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• v.24 no.1
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• pp.9-35
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• 2010

Objectives The purpose of this study is to investigate the effect of SPDJTK(SoPungDoJeokTangKami) and concurrent administration of AJ(Atopy cream, Jawoongo)+SPDJTK on atopic dermatitis-like skin lesions by using in NC/Nga atopic dermatitis mouse induced by BMAC-induced mice. Methods Clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mice were evaluated. Moreover, the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue were used in NC/Nga mice. Results Orally administrated SPDJTK with concurrent administration of SPDJTK and AJ decreased the clinical skin score, total cell number of WBC, eosinophils in blood, serum total IgE & IgG1, IL-5, IL-13, IFN-$\gamma$. Also, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, CD3+CD69+, CD3+CCR3+, CCR3+, CD4+CXCR5+ in ALN, absolute cell number of CD3+CCR3+, CCR3+ in DLN, granulocytes in PBMCs, activation cell number of CD3+CD69+, CCR3+, total cell number of CD3+ T cell in dorsal skin tissue were significantly decreased. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, amount of Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue, gene expression of IL-5, IL-13 mRNA in ALN, CD4+ Th cell in dorsal skin tissue and CCR3+ eosinophils in ALN were all significantly decreased. However, total number of DLN, absolute number of CD3e+ T cell and CD19+ B cell, absolute number of CD4+, number of Th cell in DLN and gene expression of foxp3 mRNA were significantly increased significantly. Conclusions Concurrent administration of SPDJTK and AJ on atopic dermatitis in NC/Nga atopic dermatitis mouse was very effective treatment for atopic dermatitis.

• Journal of Haehwa Medicine
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• v.18 no.1
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• pp.29-41
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• 2009

Wished to examine closely effect that SoPungDoJeokTang-KaMi (SPDJTK) medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. SPDJTK medicines controlled $CD4^+/IFN-\gamma$, and $CD4^+/CD25^+/foxp3^+$ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates T cells of a NC/Nga mouse same time by anti-CD40/rmIL-4, and interleukin-$1{\beta}$, IL-6, TNF-$\alpha$, and TGF-$\beta$ mRNA outturn that bear in T and B cells decreased remarkably by SPDJTK medicines. Intracellular staining of splenocytes anti-CD40/rmIL-4 plus rmIL-4 stimulated as described in a, assessed after 24 h, SPDJTK exerts a mainly immunosuppressive effect that acts at least partially through suppression of the transcription factor GATA3 expression in $CD4^+$ T cells. Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result that Th1 cell and Th2 cell observe to be shifted by cytokine expression with $CD4^+/CD25^+/foxp3^+$ Treg cells induction by SPDJTK medicines could know that SPDJTK medicines can use usefully in allergy autoimmnune diease.

• Parasites, Hosts and Diseases
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• v.45 no.4
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• pp.255-266
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• 2007

The protective effect of the Synadenium carinatum latex lectin (ScLL), and the possibility of using it as an adjuvant in murine model of vaccination against American cutaneous leishmaniasis, were evaluated. BALB/c mice were immunized with the lectin ScLL (10, 50, 100$[\mu}g$/animal) separately or in association with the soluble Leishmania amazonensis antigen (SLA). After a challenge infection with $10^6$ promastigotes, the injury progression was monitored weekly by measuring the footpad swelling for 10 weeks. ScLL appeared to be capable of conferring partial protection to the animals, being most evident when ScLL was used in concentrations of 50 and 100${\mu}g$/animal. Also the parasite load in the interior of macrophages showed significant reduction (61.7%) when compared to the control group. With regard to the cellular response, ScLL 50 and 100 ${\mu}g$/animal stimulated the delayed-type hypersensitivity (DTH) reaction significantly (P < 0.05) higher than SLA or SLA plus ScLL 10 weeks after the challenge infection. The detection of high levels of IgG2a and the expression of mRNA cytokines, such as IFN-$\gamma$, IL-12, and TNF-$\alpha$ (Th1 profiles), corroborated the protective role of this lectin against cutaneous leishmaniasis. This is the first report of the ScLL effect on leishmaniasis and shows a promising role for ScLL to be explored in other experimental models for treatment of leishmaniasis.