• Title/Summary/Keyword: CD4+ T cells

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Pathologic studies in lymph nodes of pigs infected with porcine circovirus type 2, porcine reproductive and respiratory syndrome virus (돼지 써코바이러스 2형과 돼지 생식기 호흡기 증후군 바이러스 감염에 따른 림프절 병변에 대한 병리학적 연구)

  • Jung, Ji-Youl;Kim, Jae-Hoon
    • Korean Journal of Veterinary Research
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    • v.53 no.4
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    • pp.245-251
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    • 2013
  • Porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) have been suspected to have immunosuppressive effects on pigs. To investigate the correlation between these virus infection and the lesions of lymph nodes including sub-mandibular and inguinal lymph node, 44 pigs (PCV2 single, n = 14; PRRSV single, n = 10; PCV2/PRRSV, n = 14; negative control, n = 6) were examined by histopathology and immunohistochemistry. Histopathologically, granulomatous lymphadenitis characterized by lymphoid depletion with histiocytic cells infiltration was observed in PCV-2 single and PCV-2/PRRSV group. Immunohistochemically, there were significant reduction of B and T lymphocytes in lymph nodes of these groups, while the number of macrophages was increased. In only PRRSV infected group, germinal center hypertrophy and lymphoid necrosis were observed. Immunohistochemically, the number of CD3+ T lymphocytes was slightly increased. Severe lymphocytic depletion in PCV-2 infection-related lymph nodes might be associated with producing immunocompromised state in pig. Comparing with PCV-2 infected group, PRRSV produced minor effects on the changes in immune cell population in the lymph nodes of pigs. PRRSV may increase susceptibility of the disease in pigs by disruption of the first defense lines in target organs, such as the alveolar macrophages in lungs.

Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro

  • Daiana V. Lopes Alves;Cesar Claudio-da-Silva;Marcelo C. A. Souza;Rosa T. Pinho;Wellington Seguins da Silva;Periela S. Sousa-Vasconcelos;Radovan Borojevic;Carmen M. Nogueira;Helio dos S. Dutra;Christina M. Takiya;Danielle C. Bonfim;Maria Isabel D. Rossi
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.425-437
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    • 2023
  • Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68+/FXIII-A- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α+ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma

  • Kim, Byoung-Ju;Kwon, Ji-Won;Seo, Ju-Hee;Choi, Won-Ah;Kim, Young-Jun;Kang, Mi-Jin;Yu, Jin-Ho;Hong, Soo-Jong
    • Clinical and Experimental Pediatrics
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    • v.54 no.9
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    • pp.373-379
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    • 2011
  • Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

Immune Responses against Marek's Disease Virus Infection (마렉병 바이러스 감염에 대한 면역 반응)

  • Jang, H.K.;Park, Y.M.;Cha, S.Y.;Park, J.B.
    • Korean Journal of Poultry Science
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    • v.35 no.3
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    • pp.225-240
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    • 2008
  • Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

Extracts of Adlay, Barley and Rice Bran have Antioxidant Activity and Modulate Fatty Acid Metabolism in Adipocytes (율무, 보리, 미강 유기용매 추출물의 항산화능과 포도당 및 지방산 대사에 미치는 영향)

  • Park, Tae-Sik;Lee, Su-Yeon;Kim, Hyun-Jin;Kim, Kyung-Tack;Kim, Young-Jun;Jeong, In-Hye;Do, Wan-Nyo;Lee, Hye-Jeong
    • The Korean Journal of Food And Nutrition
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    • v.22 no.3
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    • pp.456-462
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    • 2009
  • Adlay, barley and rice bran were extracted using various concentrations of methanol(10% and 80%) and chloroform : methanol(2 : 1) to examine the biological activities of these raw grains. Extraction with 80% methanol resulted in high Vitamin C Equivalent Antioxidant Capacity(VCEAC), in the order of barley > rice bran > adlay, as determined by DPPH and ABTS assays. In addition, the extracts of adlay and rice bran showed high cellular antioxidant activity in HepG2 cells possibly due to the presence of polyphenol glycosides in these grains. We examined the expression of glucose/fatty acid metabolizing genes in differentiated 3T3-L1 adipocyte cells. Glut1 was downregulated after treatment with rice bran and no changes in the expression of Glut4 was observed. In contrast, genes involved in fatty acid metabolism, CD36 and aP2, were upregulated. Since these physiological changes were matched with peroxisome proliferator activating receptor $\gamma$(PPAR $\gamma$) agonism, we suggest that the extracts from adlay, barley and rice bran may play preventive roles against aging and diabetes via antioxidant activity and increased uptake of fatty acids by adipocytes.

The effects of human milk proteins on the proliferation of normal, cancer and cancer stem like cells

  • Kang, Nam Mi;Cho, Ssang-Goo;Dayem, Ahmed Abdal;Lee, Joohyun;Bae, Seong Phil;Hahn, Won-Ho;Lee, Jeong-Sang
    • Analytical Science and Technology
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    • v.31 no.6
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    • pp.232-239
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    • 2018
  • Human breast milk (HBM) provides neonates with indispensable nutrition. The present study evaluated the anti-cancer activity of diluted and pasteurized early HBM (< 6 weeks' lactation) on human breast cancer cell lines. The cell lines MCF7 and MDA-MB231 were exposed to 1 % HBM from the 1st, 3rd, and 6th weeks of lactation and exhibited reduced proliferation rates. As controls, breast cell lines (293T and MCF-10A), breast cancer cell lines (MCF-7 and MDA-MB-231), and $CD133^{hi}CXCR4^{hi}ALDH1^{hi}$ patient-derived human cancer stem-like cells (KU-CSLCs) were treated with prominent milk proteins ${\beta}$-casein, ${\kappa}$-casein, and lactoferrin at varying doses (10, 50, and $100{\mu}g$) for 24 or 48 hrs. The impact of these proteins on cell proliferation was investigated. Breast cancer cell lines treated with ${\kappa}$-casein and lactoferrin exhibited significantly reduced viability, in both a dose- and time-dependent manner. Interestingly, ${\kappa}$-casein selectively impacted only cancer (but not normal breast) cell lines, particularly the more malignant cell line. However, ${\beta}$-casein-exposed human breast cancer cell lines exhibited a significantly higher proliferation rate. Thus, ${\kappa}$-casein and lactoferrin appear to exert selective anti-cancer activities. Further studies are warranted to determine the mechanisms underlying ${\kappa}$-casein- and lactoferrin-mediated cancer cell-selective cytotoxic effects.

Etiologic and Immunologic Characteristics of Thoroughbred Horses with Bacterial Infectious Upper Respiratory Disease at the Seoul Race Park

  • Ryu, Seung-Ho;Koo, Hye-Cheong;Park, Young-Kyung;Kim, Jun-Man;Jung, Woo-Kyung;Davis, William C.;Park, Yong-Ho;Lee, Chang-Woo
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.1041-1050
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    • 2009
  • Equine respiratory disease is a common cause of poor performance and training interruptions. The higher incidence rate of infectious upper respiratory disease (IURD) in thoroughbred racehorses at the Seoul Race Park coincided with the frequent stabling season, shorter stabling periods, and younger ages in this study. Incidence rates were also correlated with significantly lower proportions of cells expressing MHC class II-, CD2 antigen-, $CD4^+$- or $CD8^+$-T lymphocyte-, and B lymphocyte in IURD patients compared with healthy control groups in the summer and fall and in 2-and-3-year-old groups. The data suggested that movement and new environments may have resulted in immunosuppression and inappropriate responses to respiratory pathogens in IURD patients. The IURD incidence decreased with age, perhaps by the acquisition of immunity, and study results suggested that immunologic protection was associated with IURD, particularly in young thoroughbred racehorses. Streptococci isolates were identified in 11 of 72 IURD horses, and 3 of these isolates were identified as Streptococcus. equi subsp. equi. S. equi subsp. zooepidemicus was isolated from 2 of 23 IURD horses in the spring (8.7%), 5 of 23 in the summer (21.7%), and 1 of 6 in winter (16.7%). S. equi subsp. zooepidemicus (5%) was also identified in 3 of 61 isolates from clinically normal horses. Racetracks should implement anti-IURD protective measures by assessing the capacity of equine immunologic protection at the Park and by limiting the introduction of specific respiratory pathogens (such as S. equi subsp. equi) by preventing the access of infected but subclinical horses with a specified respiratory pathogen-free certification system prior to Park entry.

Inhibitory Effects of β-Cyclodextrin-Helenalin Complexes on H-TERT Gene Expression in the T47D Breast Cancer Cell Line - Results of Real Time Quantitative PCR

  • Ghasemali, Samaneh;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Tafsiri, Elham;Zarghami, Nosratollah;Rahmati-Yamchi, Mohamad;Alizadeh, Effat;Barkhordari, Amin;Tozihi, Majid;Kordi, Shirafkan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6949-6953
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    • 2013
  • Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

IgG4-related Ophthalmic Disease Associated with Adult Xanthogranulomatous Disease (황색육아종과 동반된 면역글로불린G4관련안질환 1예)

  • Lee, Seunghyun;Chung, Sokjoong;Heo, Jinhyung;Lew, Helen
    • Journal of The Korean Ophthalmological Society
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    • v.59 no.11
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    • pp.1071-1076
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    • 2018
  • Purpose: To report a case of immunoglobulin G4 (IgG4)-related ophthalmic disease associated with adult xanthogranulomatous disease. Case summary: A 38-year-old male with a history of cholecystectomy visited our clinic for bilateral periorbital swelling. Histopathology of the orbital biopsy showed diffuse infiltration of foamy histiocytes with Touton giant cells and lymphoid follicles, with a diagnosis of adult-onset xanthogranuloma. After excisional biopsy, he was treated with azathioprine and prednisolone. Four years after treatment, he again visited the clinic due to bilateral, yellowish eyelid masses. Serological examinations were all nonspecific findings, except for elevation of IgG and IgG4 levels. Magnetic resonance imaging showed bilateral symmetric soft tissue enlargement with slightly heterogeneous T1/T2 isosignal intensity, with contrast enhancement at the superolateral aspect of extraconal spaces. Excisional biopsy and blepharoplasty were performed. Immunohistochemical sections showed that the IgG4+/IgG plasma cell ratio was 10-20% and the IgG4 plasma cell count was 22/high power field (HPF). His past sections of 2013 from the pathology department were again stained and showed that the IgG4+/IgG plasma cell ratio was 40-50% and the IgG4 plasma cell count was 59/HPF. Thus, he was definitely diagnosed with IgG4-related ophthalmic disease. Conclusions: If there is recurrent eyelid swelling, IgG4-related ophthalmic disease should be considered as a differential diagnosis. And the patient with adult xanthogranulomatous disease can be diagnosed with IgG4-related ophthalmic disease.

Development of mixed Th1/Th2-type immune response in mice following immunization with GP63 from Leishmania donovani (내장리슈만편모충 유래 GP63 항원을 마우스에 접종한 후 관찰되는 Th1/Th2-type 복합 면역반응)

  • Shin, Sung-shik
    • Korean Journal of Veterinary Research
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    • v.41 no.2
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    • pp.211-218
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    • 2001
  • The $M_r$ 63,000 glycoprotein (GP63) and lipophosphoglycan (LPG) of Leishmania donovani were evaluated as vaccine candidates against visceral leishmaniasis. Mice were immunized with liposomeencapsulated GP63 and/or LPG that were purified from the soluble extract of L. donovani promastigotes, and were challenged with virulent amastigotes. Mice immunized with GP63/LPG in liposomes plus BCG resulted in a 27.4% reduction of amastigotes in the liver compared to the control group (liposomes plus BCG), and mice immunized with liposome-GP63 plus BCG failed to induce a protective immune response against the challenge infection. Immunization of mice with GP63 fused to the Schistosoma japonicum glutathione S-transferase (GP63-GST) plus BCG also failed to elicit protective immunity. To analyze the cause of failure to induce protection, cytokine release from the spleen cells of immunized mice and Leishmania-specific serum antibodies were analyzed. Spleen cells from mice immunized with GP63-GST plus BCG that were exposed to soluble extract of L. donovani in vitro produced 10-fold greater quantities of IFN-gamma and 3-fold greater quantities of IL-5 than cells from mice receiving BCG only or saline. Western blot analysis revealed that sera from these mice had Leishmania-specific antibodies recognizing 1 to 3 antigens of L. donovani with M. W. of 60-65 kDa. Although immunization of mice with GP63-GST induced a strong Th1 response, this study indicated that GP63-GST simultaneously elicited the Th2 response of the CD4+ T-cell, which was known to abrogate the protective immune response conferred by the Th1 effector function.

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