• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.136-145
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• 2010

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called $V{\alpha}14J{\alpha}18$ in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, ${\alpha}-galactosylceremide$ (${\alpha}-GalCer$), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and $interferon-{\gamma}$. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with ${\alpha}-GalCer$. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

• Tuberculosis and Respiratory Diseases
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• 제41권5호
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• pp.484-488
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• 1994

연구배경 : 최근에 ${\gamma}{\delta}$ T 램프구가 결핵균의 항원과 반응함이 알려져 ${\gamma}{\delta}$ T 림프구가 결핵균에 대한 방어기전에 관여할 가능성이 제시되고 있다. 본 교실의 연구와 다른 연구에 의하면 폐결핵 환자의 말초혈액에서 ${\gamma}{\delta}$ T 림프구의 숫적 증가나 기능의 활성화가 관찰되지 않아 폐결핵 환자에서 ${\gamma}{\delta}$ T 림프구는 전신적으로 활성화되지 않고 국소병변에서 방어기능을 나타내는 것으로 생각할 수 있다. 이에 저자들은 일차적으로 결핵의 국소병변으로 조직을 얻기가 쉬운 결핵성 림프절에서 ${\gamma}{\delta}$ T 림프구의 분포를 관찰하고자 본 연구를 시행하였다. 방법 : 조직검사상 결핵성 림프절염(n=5)과 반응성 과형성(reactive hyperplasia) (n=3)으로 진단된 환자의 림프절을 대상으로 CD4, ${\alpha}{\beta}$ TCR, ${\gamma}{\delta}$ TCR에 대한 단일 클론항체를 이용해 면역조직화학검사를 시행하였다. 결과 : 반응성 과형성 림프절에서는 총 T 림프구중 ${\gamma}{\delta}$ T 림프구의 비율이 $1.7{\pm}1.5%$였고 결핵성 림프절에서는 ${\gamma}{\delta}$ T 림프구가 전체 T 림프구의 $16.3{\pm}10.3%$를 차지하고 있어 결핵성 림프절에서 반응성 과형성 림프절에 비해 ${\gamma}{\delta}$ T 림프구의 침윤이 유의하게 증가되어 있었다(p<0.05). 결론 : ${\gamma}{\delta}$ T 림프구가 결핵균 감염 국소 병변부위에서 방어기전에 관여할 가능성이 있을 것으로 생각되고 향후 국소 결핵 병변에서의 ${\gamma}{\delta}$ T 림프구 기능에 관한 연구가 필요할 것으로 생각된다.

• Molecules and Cells
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• 제37권1호
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• IMMUNE NETWORK
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• 제1권1호
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• pp.61-69
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• 2001

Background: To determine the molecular structure of type II collagen-specific T-cell receptors associated with rheumatoid arthritis (RA). Methods: We generated CII-specific T-cell lines of 8 RA patients by prolonged in vitro culture with bovine CII (bCII) and the immunogenic peptide (256-270) of human CII. The proliferation response towards CII stimulation was measured from the uptake of 3H-thymidine. Changes in the secretion of Th 1 and Th2 cytokines in the culture supernatent were measured by ELISA. The TCR clonotypes of these T-cells were examined by RT-PCR/SSCP analyses of all 22 $V_{\beta}$ chains. Results: T-cells from patients' tissue exhibited strong proliferation index upon CII stimulation, which was maintained up to 6 months in the culture. The secretion of INF-$\gamma$from these T-cells increased along with the duration of culture time, while the amount of IL-4 production did not show significant changes. The SSCP band patterns of patients' T-cells appear as discrete bands unlike the smeary streak produced from normal samples. Some SSCP bands, each representing selected expansion of a TCR containing certain subtype of $V_{\beta}$ peptides, appeared to be identical in more than one patients. Among these, the expansion of SSCP band representing the $V_{\beta}$ 14 CDR3 region persisted after switching the antigen to the immunogenic human peptide (256-270). Conclusion: CII-reactive T-cells expressing distinct CDR3 motifs are selectively expanded in the peripheral blood and synovial fluid of RA patients, and their persistent proliferation upon CII stimulation, as well as the production Th 1-type cytokines, may play pivotal roles in RA pathogenesis.

• Journal of Ginseng Research
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• 제40권1호
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.

• IMMUNE NETWORK
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• 제2권4호
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• pp.217-222
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• 2002

Background: Scid.adh is a recently developed murine thymic lymphoma cell line, which has been used as in vitro model for the study of double negative stage III thymocytes. In this study, we compared the expression profile of a number of genes and proteins, which are tightly related to T cell development and apoptosis, in thymic lymphoma cell lines, R1.1, EL-4, and Scid.adh for the developmental staging. Methods: We examined the expression of development marker genes and proteins in three lymphoma cell lines by flow cytometry and RT-PCR. In addition, the expression of apoptosis-related molecules including bcl-2, bax and Fas was also investigated. Results: As previously reported, Scid.adh cell line expressed CD8 and CD25 but not TCR ${\alpha}$ chain, while R1.1 cells expressed TCR ${\alpha}$ chain and both CD4 and CD8 transcripts. These suggest that R1.1 might be in double positive stage, and low level of CD44 expression and the absence of CD25 support this suggestion. In contrast, EL-4 cells showed high level of TCR ${\alpha}$ chain transcript, and low-level of CD4 expression, suggesting that EL-4 is in more mature stage than R1.1. Further, this suggestion was supported by the lack of mT-20 in EL-4 cells, which is expressed in the immature thymocytes, and Scid.adh and R1.1 cell lines, but not in the terminally differentiated thymocytes and peripheral T cells. Among the apoptosis-related gene, transcripts of bcl-2 gene were detected in both R1.1 and EL-4 but not in Scid.adh cells, while bax was expressed in all cell lines. Fas expression was the highest in EL-4 cells and low in Scid.adh cell line. Conclusion: R1.1 cell may represent double positive stage, and EL-4 is more differentiated cell line. In addition, Scid.adh and EL-4 cell lines are suspected to be useful for the study of function of bcl-2 family and Fas during the thymocyte development, respectively.

• 농업과학연구
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• 제47권2호
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• pp.361-373
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• 2020

Integrins such as lymphocyte function-associated antigen -1 (LFA-1) have an essential role in T cell immunity. Integrin activation, namely, the transition from the inactive conformation to the active one, takes place when an intracellular signal is generated by specific receptors such as T cell receptors (TCRs) and chemokine receptors in T cells. In an effort to explore the molecular mechanisms underlying the TCR-mediated LFA-1 activation, we had previously established a high-throughput cell-based assay and screened a chemical library deposited in the National Institute of Health in the United States. As a result, several hits had been isolated including HIKS-1 (Benzo[b]thiophene-3-carboxylic acid, 2-[3-[(2-carboxyphenyl) thio]-2,5-dioxo-1-pyrrolinyl]-4,5,6,7-tetrahydro-,3-ethyl ester). In an attempt to reveal the mode of action of HIKS-1, in this study, we did drug affinity responsive target stability (DARTS) assay finding that HIKS-1 interacted with the IQ motif containing GTPase activating protein 1 (IQGAP1), a 189 kDa multidomain scaffold protein critically involved in various signaling mechanisms. Furthermore, the cellular thermal shift assay (CETSA) provided compelling evidence that HIKS-1 also interacted with IQGAP1 in vivo. Taken together, it can be concluded that HIKS-1 interferes with the TCR-mediated LFA-1 activation by interacting with IQGAP1 and thereby disrupting the signaling pathway for LFA-1 activation.

• Molecules and Cells
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• 제20권3호
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• pp.339-347
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• 2005

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.

• IMMUNE NETWORK
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• 제4권2호
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• pp.81-87
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• 2004

Background: In the thymus, developing thymocytes continually interact with thymic epithelial cell components. Self MHC restriction of mature T cells are imposed in the thymus through interaction of immature double positive thymocytes and thymic cortical epithelial cells. The site of negative selection, however, is a matter of debate. Through systemic injection of anti-TCR antibody or antigenic peptides, investigators suggested that most of the negative selection occurs in the thymic cortex. But the requirements for negative selection, i.e cellular counterparts and costimulatory molecules are more available in the medulla or cortico-medullary junction rather than in the thymic cortex. Methods: The direct and indirect pathways of thymocyte death after systemic anti-TCR antibody injection were separated through several experimental systems. B6 mice were either adrenalectomized or sham-adrenalectomized to evaluate the role of endogenous glucocorticoids from adrenal gland. Role of TNF were evaluated through using TNF receptor double knockout mice. Results: We found that without indirectly acting mediators such as $TNF-\alpha$ or corticosteroid, double positive thymocyte death were minimal by systemic injection of anti-TCR antibody in TNF receptor double knockout neonatal mice. Also by analyzing neonatal wild-type mice with adoptively transferred mature T cells, only peripheral activation of mature T cells could induce extensive double positive thymocyte death. Conclusion: Thus, systemically injected anti-TCR antibody mediated thymocyte death are mostly induced through indirect pathway.

• IMMUNE NETWORK
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• 제23권2호
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• pp.12.1-12.17
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• 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.