• Journal of Veterinary Clinics
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• v.8 no.1
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• pp.1-10
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• 1991

The B-lymphocyte differentiation from committed B-cell progenitors to antibody-secreting cells was discussed. B-cell progenitors derived from hematopoietic stem cells undergo the rearrangement of immunoglobulin(Ig) gene. The earliest cells as B-cell precursors have cytoplasmic Is(${\mu}$ chain). The entire Is molecule is expressed on the surface after synthesis of L chain. The resting B cells(Go stage) stimulated by binding antigen via Ig-receptors are activated(G$_1$ stage) and followed by proliferation(S stage), coupled with further selection(affinity maturation. class switch). The production of antibody against a particular antigen depends on the activation of B cells with surface Is capable of reacting with that antigen. This process does not occur in isolation but is controlled by helper and suppressor T cells and antigen presenting cells(APC). The mechanism of T cell-dependent B-cell response for production of antibody is largely explained by the cell to cell cooperation and soluble helper factors of T cells. 1) The antigen specific B cells and helper T cells are linked by Is-receptors, leading to the delivery of helper signals to the B cells. 2) Helper T cells recognize the processed antigen-derived peptides with the MHC class II molecules(la antigen) and is stimulated to secrete B-cell proliferation and differentiation factors which activate B cells of different antigenic specificity. The two models are shown currently 1) At low antigen concentration, only the antigen-specific B cell binds antigen and presents antigen-derived peptides with la molecules to helper T cells, which are stimulated to secrete cytokines(IL-4, IL-5, etc.) and 2) At high antigen concentration, antigen-derived peptides are presented by specific B cells, by B cells that endocytose the antigens, as well as by APC Cytokines secreted from helper T cells also lead to the activation of B cells and even bystander B cells in the on- vironmment and differentiate them into antibody-secreting plasma cells.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.44-52
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• 2004

Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

• Molecules and Cells
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• v.40 no.1
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• pp.37-44
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• 2017

PDK1 is essential for T cell receptor (TCR)-mediated activation of $NF-{\kappa}B$, and PDK1-induced phosphorylation of $PKC{\theta}$ is important for TCR-induced $NF-{\kappa}B$ activation. However, inverse regulation of PDK1 by $PKC{\theta}$ during T cell activation has not been investigated. In this study, we found that $PKC{\theta}$ is involved in human PDK1 phosphorylation and that its kinase activity is crucial for human PDK1 phosphorylation. Mass spectrometry analysis of wild-type $PKC{\theta}$ or of kinase-inactive form of $PKC{\theta}$ revealed that $PKC{\theta}$ induced phosphorylation of human PDK1 at Ser-64. This $PKC{\theta}$-induced PDK1 phosphorylation positively regulated T cell activation and TCR-induced $NF-{\kappa}B$ activation. Moreover, phosphorylation of human PDK1 at Ser-64 increased the stability of human PDK1 protein. These results suggest that Ser-64 is an important phosphorylation site that is part of a positive feedback loop for human PDK1-$PKC{\theta}$-mediated T cell activation.

• Korean Journal of Head & Neck Oncology
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• v.36 no.2
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• pp.45-50
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• 2020

Extranodal Natural Killer (NK)/T-cell lymphoma, nasal type, is a subtype of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus. Extranodal NK/T-cell lymphoma mostly affects the nasal cavity and there has been no report of the disease's occurrence at the base of tongue. Here we report a case of 43-year-old man who presented with a diffuse ulcerative lesion at the base of tongue. Because the patient had oral bleeding, tracheostomy and lingual artery ligation was performed via a transcervical approach to control bleeding and protect the upper airway. We performed a deep biopsy through the lateral pharyngotomy approach, and finally, the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. We report this rare case of extranodal NK/T cell lymphoma at the base of tongue with a literature review.

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.640-645
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• 2004

Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and／or cell cycle arrest. Trichostatin A, an antifungal antibiotic, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. In this study, we have examined the antiproliferative activities of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer, T47D cells. Both trichostatin A and HC-toxin showed potent antiprolifer-ative efficacy and cell cycle arrest at $G_2/M$ in T47D human breast cancer cells in a dose-dependent manner. Trichostatin A caused potent apoptosis of T47D human breast cancer cells and trichostatin A-induced apoptosis might be involved in an increase of caspase-3／7 activity. HC-toxin evoked apoptosis of T47D cells and HC-toxin induced apoptosis might not be medi-ated through direct increase in caspase-3/7 activity. We have identified potent activities of anti-proliferation, apoptosis, and cell cycle arrest of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer cell line T47D.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.466-473
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• 2019

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

• Animal cells and systems
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• v.8 no.2
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• pp.125-133
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• 2004

We have extended our previous work that cross-linking CD4 molecules using specific MAb induced antigen nonspecific, MHC unrestricted killing of virally infected target cells by CD$4^+$We have extended our previous work that cross-linking CD$4^+$ molecules using specific MAb induced antigen nonspecific, MHC unrestricted killing of virally infected target cells by CD$4^+$ T cells. The killing activity of antibody activated CD$4^+$T cells was completely blocked by herbimycin A, a protein tyrosine kinase (PTK) inhibitor, but not by bisindolylamaleimide, a protein kinase C (PKC) inhibitor. Herbimycin A treated human or bovine peripheral blood CD$4^+$T cells lacked PTK activity and failed to kill virally infected target cells even after cross-linking of CD4 molecules. The CD$4^+$cross-linking failed to induce effector cell proliferation or the transcription of TNF${\beta}$ Upregulation of TNF${\beta}$ was induced by incubating the antibody activated effector cells with BHV-1 infected D17 target cells for 10 h. Anti-TNF${\beta}$ antibody partially abolished (13-44%) the direct effector cell-mediated antiviral cytotoxicity. However, this antibody neutralized 70 to 100% of antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on the effector and target cell ratio. These results support the hypothesis that increased p$56^ICK enzyme activity in effector cells transduces a signal critical for effector cell recognition of viral glycoproteins expressed on the target cells. Following target cell recognition, lytic cytokines known to participate in target cell killing were produced. A better understanding of the killing activity displayed by CD$4^+$T lymphocytes following surface receptor cross-linking will provide insight into the mechanisms of cytotoxic activity directed toward virally-infected cells.T cells. The killing activity of antibody activated CD$4^+$T cells was completely blocked by herbimycin A, a protein tyrosine kinase (PTK) inhibitor, but not by bisindolylamaleimide, a protein kinase C (PKC) inhibitor. Herbimycin A treated human or bovine peripheral blood CD4T cells lacked PTK activity and failed to kill virally infected target cells even after cross-linking of CD4molecules. The CD4 cross-linking failed to induce effector cell proliferation or the transcription of TNF$\beta$. Upregulation of TNF$\beta$ was induced by incubating the antibody activated effector cells with BHV-1 infected D17 target cells for 10 h. Anti-TNF$\beta$ antibody partially abolished (13-44%) the direct effector cell-mediated antiviral cytotoxicity. However, this antibody neutralized 70 to 100% of antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on the effector and target cell ratio. These results support the hypothesis that increased $56^ICK enzyme activity in effector cells transduces a signal critical for effector cell recognition of viral glycoproteins expressed on the target cells. Following target cell recognition, lytic cytokines known to participate in target cell killing were produced. A better understanding of the killing activity displayed by CD$4^+$T lymphocytes following surface receptor cross-linking will provide insight into the mechanisms of cytotoxic activity directed toward virally-infected cells.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.529-543
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• 2020

In contrast to ventricular myocytes, the structural and functional importance of atrial transverse tubules (T-tubules) is not fully understood. Therefore, we investigated the ultrastructure of T-tubules of living rat atrial myocytes in comparison with ventricular myocytes. Nanoscale cell surface imaging by scanning ion conductance microscopy (SICM) was accompanied by confocal imaging of intracellular T-tubule network, and the effect of removal of T-tubules on atrial excitation-contraction coupling (EC-coupling) was observed. By SICM imaging, we classified atrial cell surface into 4 subtypes. About 38% of atrial myocytes had smooth cell surface with no clear T-tubule openings and intracellular T-tubules (smooth-type). In 33% of cells, we found a novel membrane nanostructure running in the direction of cell length and named it 'longitudinal fissures' (LFs-type). Interestingly, T-tubule openings were often found inside the LFs. About 17% of atrial cells resembled ventricular myocytes, but they had smaller T-tubule openings and a lower Z-groove ratio than the ventricle (ventricular-type). The remaining 12% of cells showed a mixed structure of each subtype (mixed-type). The LFs-, ventricular-, and mixed-type had an appreciable amount of reticular form of intracellular T-tubules. Formamide-induced detubulation effectively removed atrial T-tubules, which was confirmed by both confocal images and decreased cell capacitance. However, the LFs remained intact after detubulation. Detubulation reduced action potential duration and L-type Ca²⁺ channel (LTCC) density, and prolonged relaxation time of the myocytes. Taken together, we observed heterogeneity of rat atrial T-tubules and membranous ultrastructure, and the alteration of atrial EC-coupling by disruption of T-tubules.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1428-1436
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• 2023

The three Gram-negative, catalase- and oxidase-positive bacterial strains RS43^T, HBC28, and HBC61^T, were isolated from fresh water and subjected to a polyphasic study. Comparison of 16S rRNA gene sequence initially indicated that strains RS43^T, HBC28, and HBC61^T were closely related to species of genus Curvibacter and shared the highest sequence similarity of 98.14%, 98.21%, and 98.76%, respectively, with Curvibacter gracilis 7-1^T. Phylogenetic analysis based on genome sequences placed all strains within the genus Curvibacter. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the three strains and related type strains supported their recognition as two novel genospecies in the genus Curvibacter. Comparative genomic analysis revealed that the genus possessed an open pangenome. Based on KEGG BlastKOALA analyses, Curvibacter species have the potential to metabolize benzoate, phenylacetate, catechol, and salicylate, indicating their potential use in the elimination of these compounds from the water systems. The results of polyphasic characterization indicated that strain RS43^T and HBC61^T represent two novel species, for which the name Curvibacter microcysteis sp. nov. (type strain RS43^T =KCTC 92793^T=LMG 32714^T) and Curvibacter cyanobacteriorum sp. nov. (type strain HBC61^T =KCTC 92794^T=LMG 32713^T) are proposed.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.349-353
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• 2012

Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.