• IMMUNE NETWORK
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• v.23 no.5
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• pp.37.1-37.11
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• 2023

Forkhead box P3-positive (Foxp3⁺)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

• Journal of Periodontal and Implant Science
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• v.29 no.2
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• pp.333-350
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• 1999

The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.

• Clinical and Experimental Pediatrics
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• v.57 no.10
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• pp.434-439
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• 2014

Treatment outcomes of pediatric cancers have improved greatly with the development of improved treatment protocols, new drugs, and better supportive measures, resulting in overall survival rates greater than 70%. Survival rates are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to risk-based treatment through multicenter clinical trials and protocols developed to prevent central nervous system relapse and testicular relapse in boys. New drugs including clofarabine and nelarabine are currently being evaluated in clinical trials, and other targeted agents are continuously being developed. Chimeric antigen receptor-modified T cells are now attracting interest for the treatment of recurrent or refractory disease. Stem cell transplantation is still the most effective treatment for pediatric acute myeloid leukemia (AML). However, in order to reduce treatment-related death after stem cell transplantation, there is need for improved treatments. New drugs and targeted agents are also needed for improved outcome of AML. Surgery and radiation therapy have been the mainstay for brain tumor treatment. However, chemotherapy is becoming more important for patients who are not eligible for radiotherapy owing to age. Stem cell transplant as a means of high dose chemotherapy and stem cell rescue is a new treatment modality and is often repeated for improved survival. Drugs such as temozolomide are new chemotherapeutic options. In order to achieve 100% cure in children with pediatric cancer, every possible treatment modality and effort should be considered.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.853-860
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• 2006

This study was performed to investigate genes which are differently expressed in human blood by administrating of OLT-2. OLT-2 was medical precipitation composed of three medicinal herbs, Ginseng Radix, Astragali Radix, Glycyrrhizae Radix, and anti-leukemia effect of it was evaluated from Byung Hun Jeon of Wonkwang University this study was approved by Institutional Review Board of Korea Institute of Oriental Medicine (Taejeon, Korea) and four male subjects participated in this study. Gene expressions were evaluated by cDNA chip, in which 24,000 genes were spotted. Hierarchical cluster and biological process against the genes, which expression changes were more than 1.6 fold, were constructed by cluster 3.0 providing Stanford University and EASE(http://apps1 .maid.nih.gov/DAVID). Five groups were clustered according to their expression patterns. Group A contained gene decreased by OLT-2 and increased genes by OLT-2 were involved in Group B, C, D. In biological process, expression of genes involved in cytokine or cell calcium signaling, such as interleukin 18 and G-protein beta 4 were increased, but protein tyrosine phosphatase receptor type c, which function is cell adhesion between antigen-presenting cell and T or B-cell, was decreased by OLT-2. This study provides the most comprehensive available survey of gene expression changes in response to anti-leukemia effect of OLT-2 in human blood.

• BMB Reports
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• v.44 no.6
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• pp.369-374
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• 2011

MHC-I molecules play a critical role in immune surveillance against viruses by presenting peptides to cytotoxic T lymphocytes. Although the mechanisms by which MHC-I molecules assemble and acquire peptides in the ER are well characterized, how MHC-I molecules traffic to the cell surface remains poorly understood. To identify novel proteins that regulate the intracellular transport of MHC-I molecules, MHC-I-interacting proteins were isolated by affinity purification, and their identity was determined by mass spectrometry. Among the identified MHC-I-associated proteins was Tmp21, the human ortholog of yeast Emp24p, which mediates the ER-Golgi trafficking of a subset of proteins. Here, we show that Tmp21 binds to human classical and non-classical MHC-I molecules. The Tmp21-MHC-I complex lacks ${\beta}_2$-microglobulin, and the number of the complexes is increased when free MHC-I heavy chains are more abundant. Taken together, these results suggest that Tmp21 is a novel protein that preferentially binds to ${\beta}_2$-microglobulin-free MHC-I heavy chains.

• Animal cells and systems
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• v.5 no.3
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• pp.253-262
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• 2001

Ligand-receptor clustering event is the most important step in leukocyte adhesion and spreading on endothelial cells. Intercellular adhesion molecule-1 (ICAM-1) has been shown to enhance leukocyte adhesion, but the molecular event during the process of adhesion is unclear. To visualize the dynamics of ICAM-1 movement during adhesion, we have engineered stable Chinese hamster ovary cell lines expressing ICAM-1 fused to a green fluorescent protein (IC1_GFP/CHO) and examined them under the fluorescence microscopy. The transfection of IC1_GFP alone in these cells was sufficient to support the adhesion of K562 cells that express $\alpha$L$\beta$2 (LFA-1) integrin stimulated by CBR LFA-1/2 mAb. This phenomenon was mediated by ICAM-1-LFA-1 interactions, as an mAb that specifically inhibits ICAM-1-LFA-1 interaction (RRl/l) completely abolished the adhesion of LFA-1＊ cells to IC1_ GFP/CHO cells. We found that the characteristic of adhesion was followed almost immediately (~10 min) by the rapid accumulation of ICAM-1 on CHO cells at a tight interface between the two cells. Interestingly, ICI_GFP/CHO cells projected plasma membrane and encircled approximately half surface of LFA-1+ cells, as defined by confocal microscopy. This unusual phenomenon was also confirmed on HUVEC after adhesion of LFA-1＊ cells. Neither cytochalasin D nor 2,3-butanedione 2-monoxime an inhibitor of myosin light chain kinase blocked LFA-1-mediated ICAM-1 clustering, indicating that actin cytoskeleton and myosin-dependent contractility are not necessary for ICAM-1 clustering. Taken together, we suggest that leukocyte adhesion to endothelial cells induces specialized form of ICAM-1 clustering that is distinct from immunological synapse mediated by T cell interaction with antigen presenting cells.

• Korean Circulation Journal
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• v.53 no.6
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• pp.351-366
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• 2023

Along with the development of immunosuppressive drugs, major advances on xenotransplantation were achieved by understanding the immunobiology of xenograft rejection. Most importantly, three predominant carbohydrate antigens on porcine endothelial cells were key elements provoking hyperacute rejection: α1,3-galactose, SDa blood group antigen, and N-glycolylneuraminic acid. Preformed antibodies binding to the porcine major xenoantigen causes complement activation and endothelial cell activation, leading to xenograft injury and intravascular thrombosis. Recent advances in genetic engineering enabled knock-outs of these major xenoantigens, thus producing xenografts with less hyperacute rejection rates. Another milestone in the history of xenotransplantation was the development of co-stimulation blockaded strategy. Unlike allotransplantation, xenotransplantation requires blockade of CD40-CD40L pathway to prevent T-cell dependent B-cell activation and antibody production. In 2010s, advanced genetic engineering of xenograft by inducing the expression of multiple human transgenes became available. So-called 'multi-gene' xenografts expressing human transgenes such as thrombomodulin and endothelial protein C receptor were introduced, which resulted in the reduction of thrombotic events and improvement of xenograft survival. Still, there are many limitations to clinical translation of cardiac xenotransplantation. Along with technical challenges, zoonotic infection and physiological discordances are major obstacles. Social barriers including healthcare costs also need to be addressed. Although there are several remaining obstacles to overcome, xenotransplantation would surely become the novel option for millions of patients with end-stage heart failure who have limited options to traditional therapeutics.

• The Korea Journal of Herbology
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• v.33 no.5
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• pp.47-52
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• 2018

Objectives : The purpose of this study is to investigate effects on the immune system of Bombyx mori L. and Liriopis seu Ophiopogonis Tuber mixture (BL) in Thymus, Lymph Nodes. Methods : Eight-week-old male Balb/c mice were divided into five groups : Group one included the normal mice (Nor). Positive control group two administrated with red ginseng (RG) 100 mg/kg. Group three administrated with Bombyx mori L. (BX) 300 mg/kg. Group four administrated with Liriopis seu Ophiopogonis Tuber (LP) 300 mg/kg. Group five administrated with the mixture of Bombyx mori L. and Liriopis seu Ophiopogonis Tuber (BL) 300 mg/kg. After 2 weeks administration, mice were sacrified and antigen receptor in Thymus, Lymph Nodes was analyzed by using Fluorescence Activated Cellorter Sorting (FACS). we counted the total of Thymus and Lymph Nodes cells. GOT (glutamlc oxaloacetic transaminase), GPT (glutamlc pyruvic transamlnase) in serum were analyzed after experiment. Results : In Effects of Nor, RG, BX, LP, BL on the ratio of CD4+CD8+, CD4+CD69+ and CD4+CD25+ T cell in Thymus and Lymphnode, BL is higher than other groups except Nor in CD4+, CD4+CD69+, CD4+CD25+ T cell. The number of Thymus and Lymph Nodes increased in BL. In the level of GOT and GPT, BL decreased comparing to others group except Nor. Conclusions : BL may have effect on T cells in Thymus, Lymph Nodes. In addition, Bombyx mori could be immune functional material with others herb materials.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.25-33
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• 1991

The immune staus is known to be decreased in malignant disease and radiation therapy (RT), used as a therapeutic tool, further decrease this-attenuated immune status. We measured the number of peripheral lymphocytes, its subsets and lymphoblast transformation for PPD, PHA, monoclonal antibodies including anti-CD3 and anti-CD2 before and after RT in 19 patients with squamous cell lung cancer to search the fine mechanism behind the RT-induced attenuation of lymphoblast transformtion for mitogens and antigen. The results were as follows; 1) The number of lymphocytes and its subsets decreased significantly after RT, but the percentages of lymhocyte subsets did not change aftr RT except interleukin-2 receptor positive T lymphocytes. 2) The function of lymphoctes, measured by lymphoblast tranformation for PHA and PPD, decrased after RT and the compositions of PBMC used for lymphoblast transformtion were not different before and after RT. 3) The mitosis of lymphocytes to anti-CD2 or anti-CD3 decreased significantly after RT. And IL-2 plus anti-CD3 increased the mitosis than that of anti-CD3 only after RT, but before RT there was no difference. In conclusion, we suggested the fine mechanism behind the RT-induced attenuation of immune response might be the dysfunction of lymphocytes in terms of impaired synthesis of IL-2 rather than the decrease of circulating lymphocyte numbers.

• BMB Reports
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• v.37 no.3
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• pp.376-382
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• 2004

The Epstein-Barr-transformed B lymphoblastoid cell lines, LCL, which express antigens, are potential antigen-presenting cells (APCs) for the induction of cytotoxic T lymphocytes in vitro. However, transfecting LCL with subsequent selection by antibiotics is notoriously difficult because the plating efficiencies of LCL are reported to be 1% or less. Therefore, this study investigated the optimal conditions for increasing the transduction efficiency of a recombinant adenovirus to LCL for use as a source of APCs. The transduction efficiencies were < 13% (SD $\pm$ 2.13) at a multiplicity of infection (MOI) of 100, while it was increased to 28% (SD $\pm$ 9.43) at an MOI of 1000. Moreover, its efficiencies to LCL that expressed the coxsackie adenovirus receptor were increased to 60% (SD $\pm$ 6.35) at an MOI of 1000, and were further increased to 70% (SD $\pm$ 4.56) when combined with the centrifugal method. The cationic liposome or anionic polymer had no effect on the transduction efficiency when compared to that of the centrifugal method. These results may be used as a convenient source of target cells for a CTL assay and/or autologous APCs for the induction of the in vitro CTL responses that are specific to viral and tumor antigens.