• 생명과학회지
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• 제25권12호
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• pp.1425-1431
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• 2015

면역 시스템의 림프구는 B 림프구와 T 림프구 두 종류로 나눌 수 있다. B 림프구는 플라즈마 세포로 분화하여 항체를 생성하는 체액성 면역을 담당하며, T 림프구는 다른 세포나 세균을 죽이는 세포성 면역을 담당한다. 고전적으로 B 림프구와 T 림프구의 작용은 한 방향으로 이뤄졌다. T 림프구는 B 림프구의 분화를 촉진하고 면역글로불린종류의 전환을 조절한다. T 림프구가 부족한 경우 B 림프구의 부족을 초래함이 보고되어 있다. 그러나 최근에 역으로 B 림프구가 T 림프구의 분화와 활성을 조절할 수 있다는 보고가 있다. 예를 들어, B 림프구는 CD8+ T 림프구의 tolerance를 직접 조절할 수 있고, TGF-β의 분비를 통해 T 림프구의 anergy를 유도할 수 있다. 본 연구는 LPS에 의해 자극된 B 림프구가 수지상세포에서 IL-12의 분비를 억제하여 Th1 림프구의 분화를 억제할 수 있음을 보여준다. 이 억제는 B 림프구와 수지상세포의 직접적인 interaction에 의해 일어나는 것이 아니며 B 림프구가 수지상세포의 성숙을 조절하여 일어나는 것도 아니다. B 림프구에서 분비되는 soluble factor가 LPS에 의해 증가되는 수지상세포의 IL-12p35 transcription을 억제한다. 이 결과들은 B 림프구가 매개하는 새로운 면역억제 기전이 존재함을 보여준다. 이것은 고전적인 방향성을 가진 T 림프구에 의한 B 림프구 작용조절로 면역반응이 결정되는 것이 아니라 T 림프구와 B 림프구가 서로 작용을 하여 면역평형을 결정하는 기전이 존재함을 보여준다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1141-1149
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• 2018

Objective: Cluster of differentiation 4 protein (CD4) gene is an important immune related gene which plays a significant role in T cell development and host resistance during viral infection. Methods: In order to unravel the relationship of CpG island methylation level of CD4 gene with its gene expression and T lymphocyte subpopulation traits, we used one typical Chinese indigenous breed (Dapulian, DP) and one commercial breed (Landrace), then predicted the CpG island of CD4 gene, determined the methylation status of CpG sites by bisulfite sequencing polymerase chain reaction (BSP), and carried out the correlation analyses of methylation frequencies of CpG sites with mRNA expression and T lymphocyte subpopulation traits. Results: There was one CpG island predicted in the upstream -2 kb region and exon one of porcine CD4 gene, which located 333 bp upstream from the start site of gene and contained nine CpG sites. The correlation analysis results indicated that the methylation frequency of CpG_2 significantly correlated with CD4 mRNA expression in the DP and Landrace combined population, though it did not reach significance level in DP and Landrace separately. Additionally, 15 potential binding transcription factors (TFs) were predicted within the CpG island, and one of them (Jumonji) contained CpG_2 site, suggesting that it may influence the CD4 gene expression through the potential binding TFs. We also found methylation frequency of CpG_2 negatively correlated with T lymphocyte subpopulation traits CD4+CD8-CD3-, CD4-CD8+CD3- and CD4+/CD8+, and positively correlated with CD4-CD8+CD3+ and CD4+CD8+CD3+ (for all correlation, p<0.01) in DP and Landrace combined population. Thus, the CpG_2 was a critical methylation site for porcine CD4 gene expression and T lymphocyte subpopulation traits. Conclusion: We speculated that increased methylation frequency of CpG_2 may lead to the decreased expression of CD4, which may have some kind of influence on T lymphocyte subpopulation traits and the immunity of DP population.

• IMMUNE NETWORK
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• 제9권2호
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• pp.53-57
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• 2009

Engagement of the immunoreceptors initiates signaling cascades resulting in lymphocyte activation and differentiation to effector cells, which are essential for the elimination of pathogens from the body. For the transduction of these immunoreceptor-mediated signals, several linker proteins termed transmembrane adaptor proteins (TRAPs) were shown to be required. TRAPs serve as platforms for the assembly and membrane targeting of the specific signaling proteins. Among seven TRAPs identified so far, LAT and LIME were shown to act as a positive regulator in TCR-mediated signaling pathways. In this review, we will discuss the functions of LAT and LIME in modulating T cell development, activation and differentiation.

• IMMUNE NETWORK
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• 제23권4호
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• IMMUNE NETWORK
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• 제23권1호
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• pp.4.1-4.15
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• 2023

Th cells, which orchestrate immune responses to various pathogens, differentiate from naive CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.

• IMMUNE NETWORK
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• 제9권2호
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• pp.35-40
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• 2009

Although Rap GTPases of the Ras family remained enigmatic for years, extensive studies in this decade have revealed diverse functions of Rap signaling in the control of cell proliferation, differentiation, survival, adhesion, and movement. With the use of gene-engineered mice, we have uncovered essential roles of endogenous Rap signaling in normal lymphocyte development of both T- and B-lineage cells. Deregulation of Rap signaling, on the other hand, results in the development of characteristic leukemia in manners highly dependent on the contexts of cell lineages. These results highlight crucial roles of Rap signaling in the physiology and pathology of lymphocyte development.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 1997년도 제37회 춘계학술발표대회
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• pp.59.2-59.2
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• 1997

• 동국한의학연구소논문집
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• 제5권
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• pp.187-196
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• 1996

Alcohol is a major risk factor for several diseases and especially excessive, long-term alcohol consumption are caues the damage of immunity such as the inhibiton of secretion of lymphokine and proliferation of immune component cell. This study observed that the inhibition of T lymphocytic differentiation and secretion of interleukin 2(IL-2) induced in thymus of ICR mouse by chronic alcohol administration. After 8% alcohol voluntary administered for 120 days, the thymic tissue immunohistochemically stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly-2(CD8), and IL-2 receptor(CD25R) after embedding with paraffin. The results were as follows. 1. The size of thymic medulla in test group reduced than control group. 2. The number of helper T lymphocyte, cytotoxic T lymphocyte, and IL-2 receptor were decreased in thymic medulla and cortico-medullary junction of test group and the degree of CD4, CD8, and CD25R positive reaction were soften in test group. These results indicated that the secretion of IL-2 in thymus was inhibited by chronic alcohol administration and subsequently prevent to differentiate from thymocytes to T lymphocytes. As this view, cell mediated immunity were reduced by chronic alcohol administration.

• Asian-Australasian Journal of Animal Sciences
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• 제26권4호
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• pp.463-469
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• 2013

Cluster of differentiation 4 (CD4) is mainly expressed on $CD4^+$ T cells, which plays an important role in immune response. The aim of this study was to detect the association between polymorphisms of the CD4 gene and T lymphocyte subpopulations in pigs, and to investigate the effects of genetic variation on the CD4 gene expression level in immune tissues. Five missense mutations in the CD4 gene were identified using DNA pooling sequencing assays, and two main haplotypes (CCTCC and AGCTG) in strong linkage disequilibrium (with frequencies of 50.26% and 46.34%, respectively) were detected in the population of Large White pigs. Our results indicated that the five SNPs and the two haplotypes were significantly associated with the proportions of $CD4^-CD8^-$, $CD4^+CD8^+$, $CD4^+CD8^-$, $CD4^+$ and $CD4^+/CD8^+$ in peripheral blood (p<0.05). Gene expression analysis showed the mRNA level of the CD4 gene in thymus was significantly higher than that in lymph node and spleen (p<0.05). However, no significant difference was observed between animals with CCTCC/CCTCC genotype and animals with AGCTG/AGCTG genotype in the three immune tissues (p>0.05). These results indicate that the CD4 gene may influence T lymphocyte subpopulations and can be considered as a candidate gene affecting immunity in pigs.

• Journal of Gastric Cancer
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• 제17권4호
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.