• IMMUNE NETWORK
• /
• v.23 no.2
• /
• pp.17.1-17.16
• /
• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• Clinical and Experimental Vaccine Research
• /
• v.12 no.1
• /
• pp.47-59
• /
• 2023

Purpose: The development and study of hepatitis C virus (HCV) vaccine candidates' individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice. Materials and Methods: HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes' CD4⁺ and CD8⁺ T-lymphocytes was assessed. Results: Donors' PBMCs showed different levels of EC expression, ranging between 0.83-2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4⁺ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8⁺ T-cells % was observed (p=0.89). Conclusion: The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals' antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4⁺ T-cell early priming.

• The Korean Journal of Pain
• /
• v.34 no.4
• /
• pp.463-470
• /
• 2021

Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system's role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4⁺CXCR5⁺PD1⁺), Th17 (CD4⁺CCR6⁺ and CD4⁺IL17A⁺), regulatory T cells (Treg: CD4⁺ CD25⁺foxp3⁺), Th1 (CD4⁺ CXCR3⁺ and CD4⁺ IFN-γ⁺) and Th2 (CD4⁺ IL-4⁺) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3⁺, CD4⁺) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.

• Korean Journal of Environmental Biology
• /
• v.37 no.4
• /
• pp.640-651
• /
• 2019

The study analyzed the relationship between harmful cyanobacteria and physicochemical factors in Lake Juam from 2005 to 2018. The research locations were designated St. 1 (Juam-Dam) and St. 2 (Sinpyong). Harmful cyanobacteria was found in four genera (Microcystis sp., Anabaena sp., Aphanizomenon sp., Oscillatoria sp.). The average standing crops of harmful cyanobacteria in both locations were 2,575 cells mL^-1 and 2,557 cells mL^-1 from 2005 to 2011. Since 2012, there has been a significant decrease that the measurements were 42 cells mL^-1 and 82 cells mL^-1 from 2012 to 2018. To analyze the reason for the decrease in harmful cyanobacteria, Pearson's correlation and t-tests were performed on data collected during the summer period (June-September). Pearson's correlation showed a significantly positive correlation with total nitrogen(TN), outflow, and storage and a negative correlation with electrical conductivity. T-tests were conducted in two different periods and showed decreases in total nitrogen, electrical conductivity, and residence time. The average rainfall was decreased from 263.3 mm (2005-2011) to 219.9 mm (2012-2018) and total nitrogen was decreased from 0.912 mg L^-1 (2005-2011) to 0.811 mg L^-1 (2012-2018) and the same variability was seen in TP (total phosphorus). Therefore, it seems that the low-rainfall decreased the nutrients (TN) and variability in the TP, resulting in a decrease in harmful cyanobacteria in Lake Juam.

• IMMUNE NETWORK
• /
• v.23 no.2
• /
• pp.12.1-12.17
• /
• 2023

Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4⁺ T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4⁺ T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.

• IMMUNE NETWORK
• /
• v.20 no.1
• /
• pp.6.1-6.20
• /
• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• IMMUNE NETWORK
• /
• v.16 no.5
• /
• pp.281-285
• /
• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• Clinical and Experimental Pediatrics
• /
• v.51 no.12
• /
• pp.1336-1341
• /
• 2008

Purpose : This study aimed to determine the frequencies of $CD4^+CD25^+$ T cells in donor graft and peripheral blood $CD4^+CD25^+$ T cells in recipients after hematopoietic stem cell transplantation (HSCT) and their association with graft-versus-host disease (GVHD). Methods : Seventeen children who underwent HSCT were investigated. $CD4^+CD25^+$ T cells in samples from donor grafts and recipient peripheral blood were assessed by flow cytometry at 1 and 3 months after transplantation. Results : $CD4^+CD25^+$ T cell frequencies in the grafts showed no significant difference between patients with and without acute GVHD (0.90% vs. 1.06%, P=0.62). Absolute $CD4^+CD25^+$ T cell number in grafts were lower in patients with acute GVHD than in those without acute GVHD ($6.18{\times}10^5/kg$ vs. $25.85{\times}10^5/kg$, P=0.09). Patients without acute GVHD showed a significant decrease in peripheral blood $CD4^+CD25^+$ T cell percentage at 3 months compared to those at 1 month after HSCT (2.11% vs. 1.43%, P=0.028). However, in patients with acute GVHD, $CD4^+CD25^+$ T cell percentage at 3 months was not different from the corresponding percentage at 1 month after HSCT (2.47% vs. 2.30%, P=0.5). Conclusion : The effect of frequencies of $CD4^+CD25^+$ T cells in donor grafts on acute GVHD after HSCT could not be identified, and the majority of peripheral blood $CD4^+CD25^+$ T cells in patients who underwent HSCT may be activated T cells related to acute GVHD rather than regulatory T cells. Further studies with additional markers for regulatory T cells are needed to validate our results.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.186-196
• /
• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Korean Journal of Veterinary Service
• /
• v.46 no.4
• /
• pp.303-314
• /
• 2023

Protective efficacy of trivalent Salmonella inactivated vaccine containing Chlorhexidine-inactivated S. Enterltidis (SE), S. Typhimurium (ST), and S. Gallinarum (SG) strains, was evaluated in this study. A total of 70 brown nick layers were divided into 7 groups, A to G, containing 10 hens per group. All hens in groups B to D were intramuscularly immunized with approximately 7×10⁸ cells (3×10⁸ cells of SE+1×10⁸ SE+1×10⁸ cells of ST+3×10⁸ cells of SG) of the trivalent vaccine in 0.5 mL of PBS. All chickens in groups E to G were injected with sterile PBS. All hens of groups B and E, groups C and F, and groups D and G were orally challenged with approximately 2 ×10⁹ CFU of wild-type SE, ST, and SG, respectively. Serum IgG titers and CD3⁺CD4⁺ T-cells, and CD3⁺CD8⁺ T-cells levels of groups B to D significantly higher than those of group A. In addition, all animals in groups A to C, E and F showed no clinical symptoms and survived after the virulent challenges, whereas one chicken in group D died and all chickens in group G died following the challenge. The protection against wild-type SE and ST in liver, spleen, cecum, and cloaca of groups B and C chickens was significant effective as compared with those in groups E and F. These indicate that the trivalent inactivated vaccine can be an effective tool for prevention of Salmonella infections by inducing robustly protective immune responses and cellular immune response in chickens.