• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.454-460
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• 1993

Abnormalities of the T cell subsets have been detected in the immunologically mediated disease sites such as periodontal lesions which are attributable to the regulatory effect of cell differentiation and specific chemokinetic effect of various cytokines. Macrophage Inflammatory protein$(MIP)-1{\alpha}$ and gammain terferon$({\gamma}-IFN)$ serve as important immunoregulatory molecules through which growth and differentiation of specific T cell subsets are known to be negatively regulated. Murine cytolytic T cell line CTLL-2 were used to perform the [$^3H$]-thymidine incorporation test, by which we obtained more comprehensive view in regulatory actions of cytokines on the T cell subset proliferation. 1. $rMIP-{\alpha}$(200ng/ml) and $r{\gamma}-IFN$(100U/ml) appreared to suppress the proliferation rate to CTLL-2 by 74 and 86% respectively, and the suppressive action of two cytokines were synergisic. 2. Culture supernatant of anti-CD3 mAb-stimulated mouse splenocyte enhanced the proliferation rate of CTLL-2 up to 10-fold with dose-dependent manner. However, culture supernatant of unstimulated splenocyte showed only 2-fold increase in the proliferation rate. 3. CTLL-2 cell proliferation was strictly IL-2 dependent.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.44.1-44.16
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• 2023

Mesenchymal stem cells (MSCs) are effective in treating autoimmune diseases and managing various conditions, such as engraftment of allogeneic islets. Additionally, autologous and HLA-matched allogeneic MSCs can aid in the engraftment of human allogeneic kidneys with or without low doses of tacrolimus, respectively. However, HLA alloantigens are problematic because cell therapy uses more HLA-mismatched allogeneic cells than autologous for convenience and standardization. In particular, HLA-mismatched MSCs showed increased Ag-specific T/B cells and reduced viability faster than HLA-matched MSCs. In CRISPR/Cas9-based cell therapy, Cas9 induce T cell activation in the recipient's immune system. Interestingly, despite their immunogenicity being limited to the cells with foreign Ags, the accumulation of HLA alloantigen-sensitized T/B cells may lead to allograft rejection, suggesting that alloantigens may have a greater scope of adverse effects than foreign Ags. To avoid alloantigen recognition, the β2-microglobulin knockout (B2MKO) system, eliminating class-I MHC, was able to avoid rejection by alloreactive CD8 T cells compared to controls. Moreover, universal donor cells in which both B2M and Class II MHC transactivator (CIITA) were knocked out was more effective in avoiding immune rejection than single KO. However, B2MKO and CIITA KO system remain to be controlled and validated for adverse effects such as the development of tumorigenicity due to deficient Ag recognition by CD8 T and CD4 T cells, respectively. Overall, better HLA-matching or depletion of HLA alloantigens prior to cell therapy can reduce repetitive transplantation through the long-term survival of allogeneic cell therapy, which may be especially important for patients seeking allogeneic transplantation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1576-1583
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• 2006

In order to investigate the effect of Goamshimshinhwan(GASSW) on SD rats with deteriorated immunity caused by methotrexate. Methotrexate was fed to the SD rats once a day for 4 days. After the immune responses of the at a dosage 1,000, 500 and 250mg/kg/10ml. and the changes on body weight and gains, spleen weight, total blood leukocyte numbers, total lymphocyte numbers, the percentage of B-cell, T-cell, CD3+CD+4 T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the bolld and spleen were observed. In addition, the serum IL-2 levels and productivity of IL-2 of splenic cells were also demonstrated in this study. The changes on body weight were increased significantly in 100 and 500mg/kg of GASSW groups and the changes on body gain were increased significantly in 1000mg/kg of GASSW groups as compared with control group. The changes on the spleen weight (absolutely or relatively) were increased significantly in all GASSW groups as compared with control group. The total blood leukocyte numbers were increased significantly in 1000 and 500mg/kg of GASSW groups as compared with control group. The total lymphocyte numbers were increased significantly in all GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW goups in spleen as compared with control group. The percentage of B-cell and T-cell were increased significantly in 1000mg/kg of GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW groups in spleen as compared with control group. The percentage of CD3+CD4+ T-cell and the serum IL-2 levels and productivity of IL-2 of splenic cells were increased significantly in 100 and 500 mg/kg of GASSW groups in the blood and spleen as compared with control group. The percentage of CD3+CD8+ T-cell were increased significantly in 1000mg/kg of GASSW groups only in spleen as compared with control groups. The CD4+/CD8+ T-cell ratios were increased significantly in 1000 and 500mg/kg of GASSW groups only in the blood as compared with control group. Goamshimshinhwan(GASSW) has immuno-stimulating effect on SD rats with deteriorated immunity caused by methotrexate.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.67-67
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• 2004

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.108-116
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• 2023

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2683-2688
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• 2016

A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV-0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with $IC_{50}$ values of $94.9{\mu}M$ and $49.0{\pm}0.2{\mu}M$, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2909-2916
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• 2016

Background: Canine malignant lymphoma is classified into B- or T-cell origin, as in the human case. Due to differences in prognosis, a suitable method needs to be developed for lineage identification. Aims: To determine the accuracy of immunophenotypic and molecular information between three methods: immunocytochemistry (ICC), immunohistochemistry (IHC) and heteroduplex polymerase chain reaction for antigen receptor rearrangements (hPARR) in spontaneous canine lymphomas. Materials and Methods: Peripheral blood, fine needle aspiration and tissue biopsies from enlarged peripheral lymph nodes prior to treatment of 28 multicentric lymphoma patients were collected. Cytopathology and histopathology were examined and classified using the updated Kiel and WHO classifications, respectively. Anti-Pax5 and anti-CD3 antibodies as B- and T-cell markers were applied for immunophenotyping by ICC and IHC. Neoplastic lymphocytes from lymph node and white blood cell pellets from peripheral blood were evaluated by hPARR. Results: In this study, low grade B-cell lymphoma accounted for 25% (7/28), high grade B-cell lymphoma for 64.3% (18/28) and high grade T-cell lymphoma for 10.7% (3/28). According to the WHO classification, 50% of all cases were classified as diffuse large B-cell lymphoma. In addition, ICC showed concordant results with IHC; all B-cell lymphomas showed Pax5+/CD3, and all T-cell lymphomas exhibited Pax5-/CD3+. In contrast to hPARR, 12 B-cell lymphomas featured the IgH gene; seven presented the $TCR{\gamma}$ gene; five cases showed both IgH and $TCR{\gamma}$ genes, and one case were indeterminate. Three T-cell lymphomas showed the $TCR{\gamma}$ gene. The percentage agreement between hPARR and ICC/IHC was 60%. Conclusions: Immunophenotyping should not rely on a single method. ICC or IHC with hPARR should be used concurrently for immunophenotypic diagnosis in canine lymphomas.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1347-1355
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• 2004

In this study, the immunological effect of a traditional Korea herbal acupuncture, that has been widely used for the treatment of various immunological disorders including inflammation in Korea, was examined in vitro and in vivo. In our previous study demonstrated that BV increased the expression of IFN-γ mRNA, that plays pivotal role in T cell response. This study was designated to evaluate the effect of BV on helper T cell development by monitoring Th1/Th2 specific cytokine secretion patterns in artificially induced Th1/Th2 polarized condition and in vivo. The results demonstrated that BV didn't have mitogenic effects on the unstimulated CD4+ T cell, but increased the CD4+ T cell proliferation upon activation with anti-CD3/CD28 antibody. The Th1 cells were over-populated dramatically in Th1 driven condition with BV treatment, while the Th2 cells were increased slightly in Th2 skewed condition. Furthermore, under Th1-skewed conditions, the level of IFN-γ was considerably increased with BV treatment. Besides, the expression of T-bet, a transcription factor that plays pivotal role in Th1 lineage programming, was increased with BV treatment. The expressions of IFN-γ and T-bet were also significantly increased in vivo. The results that Th1 specific cytokine secretion were considerably increased and Th2 specific cytokine secretion were not significantly changed in vitro and in vivo indicated that BV enhances Th1 lineage development, Therefore, these results suggest that BV might be desirable agent for correction of Th1 dominant pathological disorders.