• Journal of Veterinary Science
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• v.19 no.6
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• pp.817-826
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• 2018

The bursa of Fabricius (BF) is a central humoral immune organ unique to birds. Four bursal peptides (BP-I, BP-II, BP-III, and BP-IV) have been isolated and identified from the BF. In this study, the immunoadjuvant activities of BPs I to IV were examined in mice immunized with H9N2 avian influenza virus (AIV) vaccine. The results suggested that BP-I effectively enhanced cell-mediated immune responses, increased the secretion of Th1 (interferon gamma)- and Th2 (interleukin-4)-type cytokines, and induced an improved cytotoxic T-lymphocyte (CTL) response to the H9N2 virus. BP-II mainly elevated specific antibody production, especially neutralizing antibodies, and increased Th1- and Th2-type cytokine secretion. BP-III had no significant effect on antibody production or cell-mediated immune responses compared to those in the control group. A strong immune response at both the humoral and cellular levels was induced by BP-IV. Furthermore, a virus challenge experiment followed by H&E staining revealed that BP-I and BP-II promoted removal of the virus and conferred protection in mouse lungs. BP-IV significantly reduced viral titers and histopathological changes and contributed to protection against H9N2 AIV challenge in mouse lungs. This study further elucidated the immunoadjuvant activities of BPs I to IV, providing a novel insight into immunoadjuvants for use in vaccine design.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.1
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• pp.221-246
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• 2004

Objective: The purpose of this study was to investigate the effects of Kamikwiryongtang (KKT) on the immune response and growth in a young mouse (3 weeks mice). Methods The viability of thymocytes and splenocytes in vivo and in vitro system, the population of helper T (Th) cells and cytotoxic T (Tc) cells in thymocytes and increased the population of T-lymphocytes and the population of Th cells in splenocytes, the production of ${\gamma}$ -interferon, interleukin-2 and interleukin-4 in splenocytes was investigated. KKT (500mg/kg) was administerd p.o. once a day for 7 days. Results: KKT increased the viability of thymocytes and splenocytes in vivo, but did not affect the viability of thymocytes and enhanced the viability of splenocytes in vitro system. In addition, KKT did not affect the population of helper T (Th) cells and cytotoxic T (Tc) cells in thymocytes and increased the population of T -lymphocytes and the population of Th cells in splenocytes. Also, KKT increased the production of ${\gamma}$-interferon, interleukin-2 and interleukin-4 in splenocytes. Furthermore, KKT increased the production of nitric oxide in vivo, but did not affect the production of nitric oxide in vitro system. KKT enhanced the phagocytic activity of peritoneal macrophages in vivo, but decreased the phagocytic activity in vitro system: KKT increased the body weight of a young mouse. Conclusions: KKT stimulates the specific immune response via increase of, the viability of thymocytes and splenocytes and the non-specific immune response via increase of phagocytic activity of peritoneal macrophages and stimulates the growth of a young mouse.

• Korean Journal of Medicinal Crop Science
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• v.26 no.1
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• pp.72-81
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• 2018

Background: Polysaccharides are the most important functional constituent in Astragalus membranaceus. The purpose of the present study was to evaluate the effect of polysaccharides isolated from the aboveground parts of A. membranaceus (AMA) and polysaccharides isolated from the roots of A. membranaceus (AMR) immune function by modulated cytotoxic T cell and Th1- and Th2-related cytokines kinetics. Methods and Results: Sprague-Dawley rats were randomly divided into exhaustive exercise case groups and non-exercise case, AMA and AMR samples were administered orally for 30 days (500 mg/kg/day and 10 mg/kg/day, respectively) and were compared to those rats in the groups fed commercial sports drink (SPD) and vehicle. Both exhaustive exercise groups and non-exercise groups had a lower ratio of $CD4^+$ and $CD8^+$ cells in the spleens of the rat fed AMA and AMR compared to those in the rats fed SPD and vehicle group. These results suggested that AMA and AMR promote an increase in the proportion of cytotoxic T cells. The IL-4-producing T lymphocytes decreased significantly in the AMR (10 mg/kg/day) group compared to SPD and vehicle, whereas the AMA group increased the IL-4 concentration more than the SPD and vehicle in exhaustive exercise group. However, the populations of IFN-${\gamma}$-producing T lymphocytes of AMR and AMA increased. AMA decreased the concentration of IFN-${\gamma}$ to inhibit the Th1 response and thereby increased the concentration of IL-4 to induce a Th2 response that was related to humoral immunity in the non-exercise group. Conclusions: These results showed that, in addition to Th1/Th2 regulation, AMR and AMA played an important immuno-modulatory role after exhaustive exercise-induced Th1/Th2 lymphocyte imbalance, which might be correlated with cytokine producing immunoregulatory cells.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.37-42
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• 2013

In this present study, we determined the immunoregulatory activity of ginsenoside Rd extract from Panax ginseng. To determine the activity, we tested Rd against $CD4^+$ Th cells in a murine model of type 1 diabetes, which involves Th1-dominant immunity. The type 1 diabetes was caused by streptozotocin (STZ) and the severity of the diabetes was evaluated by measuring the degree of hyperglycemia, a major symptom of diabetes. The data resulting from experiments showed that ginsenoside Rd induced a greater level of Th1 type cytokines [IFN-${\gamma}$ & IL-2] than Th2 type [IL-4 & IL-10] (P<0.05), which was determined by cytokine profile analysis. In the animal model of diabetes, the depletion of $CD4^+$ Th cells by a treatment of anti-CD4 mAb resulted in considerably lower values of blood-glucose levels than those of the mAb-untreated mice, which indicates that the Th1 immune response from $CD4^+$ Th cells are responsible for diabetes. Based on these observations, the effect of Rd on diabetes was examined in the same animal model. Results showed that Rd-treated mice groups had increased levels of blood glucose compared to Rd-untreated mice groups that were used as a negative control (P<0.05). In other words, Rd aggravated the diabetes via the Th1 immune response. In conclusion, ginsenoside Rd had an immunoregulatory activity of Th1-dominant immunity.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.249-256
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• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.13-25
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• 1999

Background: Ineffective cell-mediated immune response in human tuberculosis is associated with a depressed Thl cytokine response and reduced production of IFN-$\gamma$. Most persons infected with Mycobacterium tuberculosis are healthy tuberculin reactors with protective immunity, but a minority with ineffective immunity develop extensive pulmonary tuberculosis. The cell-mediated immune response is an important aspect of host resistance to mycobacterial infection and is believed to be tightly regulated by a balance between Th1 cytokines including IFN-$\gamma$, IL-12, IL-18, regulated on activation, normal T cell expressed and secreted (RANTES) and Th2 counterparts such as IL-4, monocyte chemoattractant protein-l (MCP-l). Methods: Proliferation and mRNA expression of IFN-$\gamma$, RANTES and MCP-l by RT-PCR in peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with mycobacterial antigens were compared in pulmonary tuberculosis patients with cured and treatment failure and in tuberculin-positive and tuberculin-negative healthy subjects. Results: Defective proliferative responsiveness to aqueous TSP antigen was involved with treatment failure tuberculosis patients. Aqueous TSP antigen-induced IFN-$\gamma$ and RANTES mRNA expression was decreased in treatment failure tuberculosis patients compared with healthy tuberculin reactors and cured tuberculosis patients (23.1 % versus 90.0% for IFN-$\gamma$ and 46.2% versus 70.0% versus 46.2% for RANTES). The frequency of MCP-l mRNA expression to aqueous TSP antigen in treatment failure tuberculosis patients was greater than in healthy tuberculin reactors and cured tuberculosis patients (76.9% versus 40.0%). Conclusion: The increasing expression of MCP-1 mRNA in response to aqueous TSP antigen might be predicted to favor Th1 responses and restricted Th1 responses in treatment failure of pulmonary tuberculosis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.11 no.1
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• pp.101-116
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• 1989

Proplast and Porous Polyethylene which have porous structures as low-modulus polymers have been recently used in maxillofacial plastic and reconstructive surgery. The purpose of this study was to compare the response of adajacent tissue, new bone formation and stability after augmentation by differen methods of subperiosteal graft using proplast and purous polythylene in rabbit mandible. The augmentation procedure was carried out by dividing into two groups, A and B. A group consisted of subperiosteal graft on the cortex, and the other B group was made up only graft following artificial decortication in the mandibular body of rabbit. The experimental animals were sacrificed on the 1st, 2nd, 4th and 8th week after grafting for macroscopic and light microscopic examination. The samples extracted at the 6th postgrafting week were also used for biometric testing and scanning electron microscopic examination. The results obtained from this study were as follows : 1. Macroscopically, infection of graft site, deformation and migration of graft material were not observed in all experimental groups. 2. B group showed more rapid and increased bone formation and the greater stability than A group, and tissue response was similar to each other. 3. In the tissue response, macrophages and cellular infiltrations were observed in Proplast group, but few in PHDPE group. 4. In bone formation of A group, Proplast group showed no bone formation until the 8th week, but PHDPE group showed small quantity of osteoid tissue from the 2nd week and appositional bone growth with new bone formation at the 8th week. 5. In bone formation of B group, both Proplast and PHDPE group showed bone formation, but PHDPE group showed more rapid and larger bone formation. 6. In pattern of bone formation, Proplast group mainly showed appositional bone growth pattern connected with graft site. On the other hand, PHDPE group showed mixed pattern of new bone formation in the pore connective tissue with appositional bone growth from graff site. 7. The maximum mean values of shear stress were serially $111.3gf/mm^{2}$ in PHDPE of B group, $84.8gf/mm^{2}$ in PHDPE of A group, $32.9gf/mm^{2}$ in Proplast B group, and $15.7gf/mm^{2}$ in Proplast of A group. From above results, It was suggested that the capacity of bone formation and stability between bone and graft material were dependent on the pore size and structure of graft material itself, the state of graft site and tissue response.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.106-115
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• 2010

Phosphorylated dextran (P-Dex) is an acidic polysaccharide that functions as an immune adjuvant. P-Dex is known to regulate immune response by maintaining a balance between Th1 and Th2 cells in vitro, and thus may also be important in the control of allergic reactions. In the current study, we report the optimum conditions required for the efficient phosphorylation of dextran without toxicity. We found that when dextran was heated at 160${^{\circ}C}$ for 24 h in phosphate buffer (pH 5.0), the resulting P-Dex demonstrated the highest phosphorus content (6.8%). We also report that P-Dex enhances mitogenic activity in mouse splenocytes and induces expression of CD69 and CD86 on the surface of B cells and dendritic cells (DC) in vitro. Oral administration of P-Dex to ovalubmin (OVA)-immunized mice was found to reduce antigen-induced cell proliferation and suppress the expression of CD86 on Th2-inducing DC via exogenous OVA stimulation. P-Dex was also found to increase IL-10 expression in the splenocytes of treated mice. These findings suggest that oral administration of P-Dex increases immunological tolerance and improves the specificity of immunological response to specific antigens.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.16.1-16.19
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• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.