• IMMUNE NETWORK
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• v.20 no.5
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• pp.38.1-38.12
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• 2020

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3⁺ induced Treg (iTreg) differentiation in ovalbumin-specific CD4⁺ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.221-231
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• 2005

Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.

• Journal of Periodontal and Implant Science
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• v.44 no.5
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• pp.235-241
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• 2014

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.1
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• pp.11-14
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• 2010

Human tumors, including those of the hepatobiliary system, express a number of specific antigens that can be recognized by T cells, and may provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. The ability to culture sufficient numbers of DCs from human bone marrow or blood progenitors has attracted a great deal of interest in their potential utilization in human tumor vaccination. $CD34^+$ peripheral blood stem cells (PBSCs) were obtained from a patient with a hepatocellular carcinoma. The PBSCs were cultured in the X-VIVO 20 medium supplemented with the Flt-3 Ligand (FL), GM-CSF, IL-4 and TNF-$\alpha$ for 12 days. The morphology and functions of the cells were examined. The generated cells had the typical morphology of DCs. When the DCs were reinjected into the same patient, an augmentation of the cytotoxic T lymphocyte (CTL) activity was observed. Concomitantly, an increase in the natural killer (NK) cell activity was also detected in the patient. These results suggest that DCs-based cancer immunotherapy may become an important treatment option for cancer patients in the future.

• Therapeutic Science for Rehabilitation
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• v.10 no.2
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• pp.7-22
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• 2021

Objective : This study aimed to analyze the effect of transcranial direct current stimulation (tDCS) on cognitive function recovery in patients with stroke. Methods : Data published in Korean and foreign academic journals from 2009 to 2019 were searched using the NDSL, RISS, PubMed, and CINAHL databases. A total of 11 experimental research articles were selected based on the inclusion and exclusion criteria. A qualitative assessment was conducted, and a meta-analysis of nine results from seven of the stuides was performed using the Comprehensive Meta-Analysis 3.0 program. Results : Based on the results of the meta-analysis, the attention and memory effect sizes were 0.725 and 0.796, respectively, which were both considered a "medium effect size". Statistically significant changes were observed in both the areas (p<0.05). Conclusion : The results of this study confirmed that tDCS can be useful in the rehabilitation of patients with stroke with limited cognitive function. In addition, the application methods differed, indicating that a formalized tDCS protocol is required.

• 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.

• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.484-488
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• 2013

Objective : To examine the synergistic effects of both computer-assisted cognitive rehabilitation (CACR) and transcranial direct current stimulation (tDCS) on cognitive function in patients with stroke. Methods : The current double-blind, sham-controlled study enrolled a total of 11 patients who were newly diagnosed with stroke. The patients of the tDCS group (n=6) completed sessions of the Korean computer-assisted cognitive rehabilitation program five times a week for 30 minutes a session during a mean period of 18.5 days concomitantly with the anodal tDCS over the bilateral prefrontal cortex combined with the CACR. The patients of the control group (n=5) also completed sessions of the sham stimulation during a mean period of 17.8 days. Anodal tDCS over bilateral prefrontal cortex (F3 and F4 in 10-20 EEG system) was delivered for 30 minutes at an intensity of 2 mA. Cathode electrodes were applied to the non-dominant arm. All the patients were evaluated using the Seoul Computerized Neuropsychological Test (SCNT) and the Korean Mini-Mental State Examination. Results : Mann-Whitney U test revealed a significant difference between the two groups. The patients of the tDCS group achieved a significant improvement in the post/pre ratio of auditory continuous performance test and visual continuous performance test on the SCNT items. Conclusion : Our results indicate that the concomitant use of the tDCS with CACR to the prefrontal cortex may provide additional beneficial effects in improving the cognitive dysfunction for patients with stroke.

• Journal of International Academy of Physical Therapy Research
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• v.2 no.1
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• pp.193-200
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• 2011

This study is intended to examine the tDCS and Montoya stair task(MST) on sensorimotor recovery and glial scar expression in MCAo induced stroke model of rat. To achieve this goal, this study selected 80 SD rats of 8 weeks. The experiment groups were divided them into four groups, and assigned 20 rats to each group. Group I was a experimental control group; GroupII was a tDCS application group after MCAo; Group III was a MST application group after MCAo; Group IV was a tDCS and MST application group after MCAo. In each group, neurological function test measurement, motor behavior test, montoya stair task test, immunohistochemistric finding of GFAP expression finding were analyzed. In motor behavior test, the outcome of group I was significantly difference than the other group, especially from 14days. In montoya stair task test, the outcome of group I was significantly lower than the other group especially, group II were significantly different on 14days and group IV was most significantly difference than the other group. In immunohistochemistric finding, group II, III, IV were decrease GFAP expression on depend on time stream. These results throughout the MCAo due to focal ischemic brain injury rat model four weeks tDCS and MST was applied, when the neurobehavioural, upper extremity function and ability, histopathologic data suggest that sensorimotor function recovery and a positive influence on glial scar decrease and confirmed that.

• The Journal of Korean Physical Therapy
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• v.23 no.1
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• pp.77-82
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• 2011

Purpose: Recently, many studies have demonstrated that application of external stimulation can modulate cortical excitability of the human brain. We attempted to observe cortical excitability using functional magnetic resonance imaging (fMRI) during the application of transcranial direct current stimulation (tDCS) or functional electrical stimulation (FES). Methods: We recruited two healthy subjects without a history of neurological or psychiatric problems. fMRI scanning was done during? each constant anodal tDCS and FES session, and each session was repeated three times. The tDCS session consisted of three successive phases (resting phase: 60sec dummy cycle: 10sec tDCS phase: 60sec). The FES session involved stimulation of wrist extensor muscles over two successive phase (resting phase: 15sec FES phase: 15sec). Results: The average map of the tDCS and FES analyses showed that the primary sensory-motor cortex area was activated in all subjects. Conclusion: Our findings show that cortical activation can be induced by constant anodal tDCS and FES. They suggest that the above stimuli have the potential for facilitating brain plasticity and modulating neural excitability if applied as specific therapeutic interventions for brain injured patients.

• The Journal of Korean Physical Therapy
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• v.26 no.6
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• pp.436-441
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• 2014

Purpose: The objective of this study was to offer clinical primary data that it's aims to examine effects of transcranial direct current stimulation (tDCS) on cognitive function and biochemical change of rat with alzheimer's disease(AD) induced by injecting scopolamine. Methods: Subjects were instructed cognitive dysfunction model, rat of Sprague-Dawley system was injected with scopolamine and each experimental group was classified into three; group I (n=16) is non-treatment groups; group II (n=16) is applied with the tacrine; group III (n=16) is applied with the tDCS. The ziggurat task test was conducted to observe behavioral changes and cognitive function ability and 7, 14, 21, 28 days after the model. Acetylcholine Esterase (Ach E) activity was examined for biochemical assessment of which the results are followed. Results: Participants showed as to behavioral change, tacrine application group was the most significantly responded, following tDCS application group. As to biochemical change, same as above, tacrine application group was the most significantly responded, following tDCS application group. Conclusion: From these results, confirm that tDCS application to rat with alzheimer's disease leads to positive effects on behavioral, cognitive function changes, and biochemical changes, lasting for certain period of time. This study, in particular, tDCS, which can change excitability of brain cells non-invasively, could provide basic data that is useful as a new treatment way for the patients with cognitive dysfunction.