• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.1-8
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• 2005

Bacterial heat shock protein has been one of the components that are responsible to induce autoimmune disease mechanisms in the pathogenesis of atherosclerosis due to high level of homology in sequence with human counterpart. This mechanism may explain how bacterial infectious disease, such as periodontal disease, might contribute to the acceleration of the disease process of atherosclerosis. Porphyromonas gingivalis which is a major periodontal pathogenic bacterial species, has been implicated as one of the pathogenic bacteria playing the role in this context. The present study has been performed to evaluate the anti-atherosclerotic effect of adoptive transfer of Porphyromonas gingivalis heat shock protein epitope-specific T cell lines into severe combined immunodeficiency (SCID) mice. Peptide no. 15 with amino acid sequence VKEVASKTND-specific T cell line was selected for the transfer. When experimental atherosclerosis was induced in SCID mice adoptively transferred either by the T cell lines (experimental group) or by non-specific mouse T cells (control group), there was no significant difference in the severity and extent of the atherosclerosis induced by hypercholesterol diet.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.25-30
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• 1998

An in vivo model for human melanoma was established with the growth and metastasis of SK-MEL-2 cells. The tumor was introduced into C.B-17 SCID(severe combined immunodeficiency) mice intraperiotneally subcutaeously and intravenous inoculations. Tumors developed in 100% of mice inoculated subcutaneously and intraeritoneally both at site of inoculation and as metastatic tumor in the liver lungs and diaphragm. With intravenous inoculation 50% of mice showed metastasis in the spleen. Additionally metastatic foci that were not detected either by gross and/or standard histopathologic examination were demonstrated in the spleen and lungs by immunohistochemistry with HMB-45 monoclonal antibody. We conclude that the SCID mouse supports growth and metastasis of human malignant melanoma SK-MEL-2 cells.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.166-175
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• 2018

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

• Journal of Life Science
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• v.20 no.3
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• pp.453-456
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• 2010

Leukemia is the abnormal increase of hematopoietic progenitor cells in tissues, resulting in anemia, increased susceptibility to infection and impaired blood clotting. The adenosine deaminase (ADA) gene is an important druggable target for the treatment of leukemia patients. Genetic and molecular analyses were performed to determine the effects of ADA gene mutations in 20 leukemia patients in the Korean population. To analyze the relationship between genotype and phenotype, the ADA genomic DNAs - including 1,092 bp of 12 exons and partial intron sequences flanking each exon - were sequenced and compared. In this study, the known mutations in other diseases, more than 50 mutations already reported in patients with severe combined immunodeficiency disease (SCID) and autism, were not found, but two novel mutations in leukemia patients were discovered. They include one nonsense mutation (A>C at nt position 478, F101F) and one missense mutation (G>A at nt position 778, E260K). One missense mutation (G>A at nt position 22, D8Y) was also detected in 20 normal control patients (allelic frequency of 7.5%). Interestingly, subjects in the Korean population retained 2 bp insertion at the intron 6 (IVS6-52insGC), something that has never been shown in other populations. The genetic study to find out the correlation between the mutant alleles and leukemia patients revealed no association statistically (p>0.05). The mutation found in leukemia needs further study to determine its possibility as a molecular marker for the diagnosis of leukemia.

• Molecules and Cells
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• v.44 no.9
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• pp.647-657
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• 2021

As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

• Reproductive and Developmental Biology
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• v.32 no.1
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• pp.1-7
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• 2008

The SCID-repopulation cells(SRCs) assay has been widely used to determine the self-renewal capacity of hematopoietic stem cells (HSCs). In this study, we tested the repopulating efficiency of porcine bone marrow derived hematopoietic stem cells using nonobese diabetic/severe combined immunodieficient (NOD/SCID) mice which was inherited immunodeficiency mire with defect of T cells, B cells, and low activity of NK cells. We transplanted porcine bone marrow hematopoietic stem/progenitor cells with intraperitoneal injection into neonate NOD/SCID mice. We confirmed efficient reconstitution activity of inoculated porcine hematopoietis cells in variety of organs of NOD/SCID mice. Interestingly, pig $CD3^+$ T lymphocytes detected with high level in liver($15.6{\pm}3.7%$), spleen($5.6{\pm}3.0%$), thymus($1.5{\pm}1.3%$), and BM($2.3{\pm}0.9%$), respectively. These data imply that microenvironment of neonate NOD/SCID mice is very efficient for proliferation and differentiation of porcine T cells, and can be useful for the study of T cells development and renogeneic organ transplantation.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.173-179
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• 2023

Complete DiGeorge syndrome (cDGS) refers to DGS with profound T cell deficiency. Herein, we present the case of an infant with cDGS suffering from refractory cytomegalovirus (CMV) infection and who was treated with CD45RA+ depleted lymphocyte infusion. The patient was diagnosed with cDGS by fluorescence in situ hybridization which verified 22q11.2 deletion and as well as by the observed profound T cell deficiency (CD3+ T cells 69/μL, CD4+ T cells 7/μL). On the 45th day of age, CMV viremia was first detected with a plasma viral load (VL) of 120,000 IU/mL. Ganciclovir treatment effectively reduced VL post 56 days of treatment; however, VL subsequently rebounded. A CMV UL97 phosphotransferase M460V mutation conferring ganciclovir resistance emerged and foscarnet was incorporated. Despite this, high titers of CMV viremia (VL 2,820,000 IU/mL) and CMV retinitis were complicated. To restore T cell immunity and treat refractory CMV infection, CD45RA+ depleted CMV-specific lymphocytes from the patient's father were infused twice on the 196th and 207th days after birth. After receiving the second infusion, a decline in CMV VL was observed, with a decrease to 87,100 IU/mL by the tenth day following infusion, despite the failure in maintaining T cell increase. The patient died of Pneumocystis jirovecii pneumonia and Elizabethkingia meningoseptica sepsis on the 222nd day after birth. CD45RA+ depleted lymphocyte infusion may be a therapeutic option for refractory CMV disease in cDGS patients.