• Food Science and Biotechnology
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• v.17 no.3
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• pp.598-602
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• 2008

Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.

• Journal of Convergence for Information Technology
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• v.10 no.6
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• pp.164-176
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• 2020

Efficient production of antigen specific cytotoxic T cells is critical for appropriate adoptive immune response. In vitro culture and expansion of human T lymphocyte clones are very sophisticated and subtle procedure in immune cell therapy and hard to control. Therefore, many groups devoted their efforts to manipulate artificial antigen presenting cells (aAPCs) that can induce T cell activation and clonal expansion. To mimicking of natural antigen-presenting cells, aAPCs encompass basic signal molecules required for T cell activation: MHC:antigen complexes, co-stimulatory molecules and soluble immune modulating molecules. Orchestrated organization of these molecules is important for efficient T cell activation. Here, we discuss how those molecules have been incorporated in several aAPC models, but also how physical properties od aAPC are important for interaction with T cells.

• Molecules and Cells
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• v.45 no.8
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• pp.513-521
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• 2022

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.

• Molecules and Cells
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• v.39 no.7
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• pp.515-523
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• 2016

Long-term immunity to many viral and bacterial pathogens requires$ CD8^+$ memory T cell development, and the induction of long-lasting$ CD8^+$ memory T cells from a $na{\ddot{i}}ve$, undifferentiated state is a major goal of vaccine design. Formation of the memory$ CD8^+$ T cell compartment is highly dependent on the early activation cues received by $na{\ddot{i}ve}$ $CD8^+$ T cells during primary infection. This review aims to highlight the cellularity of various niches within the lymph node and emphasize recent evidence suggesting that distinct types of T cell activation and differentiation occur within different immune contexts in lymphoid organs.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.148-153
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• 1996

Activation of the T lymphocytes results in a variety of early biochemical events ultimately leading to cell proliferation and lymphokine production. Stimulation of the signal transduction cascade in T cells through the T cell receptor coincides with activation of the phosphatidylinositol-phospholipase C (PI-PLC) pathway. Therefore, we have established a model system to screen immune-simulator that can increase the hydrolysis of phosphoinositides in human T cell leukemia Jurkat cells. As a result of screening from herbal medicine extract, 4 extracts (O1ibanum, Ephedrae Herba, Real Gar, Saussureae Radix) were found 14 increase the production of inositol phosphates. All the active fraction from the four kinds of extract were fluted in a different retention time on C-18 HPLC and these active fraction also showed difference in cell specificity. And all the active fractions increased DNA synthesis in T cell. Therefore, it is suggested that the active fraction among 4 extracts might contain a compound having different properties one another.

• IMMUNE NETWORK
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• v.16 no.2
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• pp.134-139
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• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.45-49
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• 1987

Employing the approach to isolate the genes expressed preferentially in cytolytic T cell (CTL) but not in other types of cell, 3 CTL-specific cDNAs were recently cloned. To characterize these cDNA clones in relation to CTL activation, their expression pattern after T cell antigen receptor (TCR) or interleukin 2 (IL-2) stimulation were investigated by RNA blot analysis of cloned CTL L3 cells. Transcripts level of two cDNA clones were markedly elevated by TCR stimulation but not by IL-2. In addition, transcripts expression of both clones were abrogated by cyclosporin A treatment. These results indicated that gene activation mediated by TCR is distinct from that mediated by IL-2 and imply that those two unidentified cDNA clones are related to TCR-mediated, IL-2-independent but cyclosporin A-sensitive pathway for CTL activation.

• Molecules and Cells
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• v.28 no.3
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• pp.183-188
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• 2009

TSAd/Lad is a T cell adaptor molecule involved in $p56^{lck}$-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the $p56^{lck}$ proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as $Ca^{2+}$ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.302-309
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• 2003

Background: CTLA4 (CD152), which is expressed on the surface of T cells following activation, has a much higher affinity for B7 molecules comparing to CD28, and is a negative regulator of T cell activation. In contrast to stimulating and agonistic capabilities of monoclonal antibodies specific to CTLA-4, CTLA4Ig fusion protein appears to act as CD28 antagonist and inhibits in vitro and in vivo T cell priming in variety of immunological conditions. We've set out to confirm whether inhibition of the CD28-B7 costimulatory response using a soluble form of human CTLA4Ig fusion protein would lead to persistent inhibition of alloreactive T cell activation. Methods: We have used CHO-$dhfr^-$ cell-line to produce CTLA4Ig fusion protein. After serum free culture of transfected cell line we purified this recombinant molecule by using protein A column. To confirm characterization of fusion protein, we carried out a series of Western blot, SDS-PAGE and silver staining analyses. We have also investigated the efficacy of CTLA4Ig in vitro such as mixed lymphocyte reaction (MLR) & cytotoxic T lymphocyte (CTL) response and in vivo such as experimental autoimmune encephalomyelitis (EAE), graft versus host disease (GVHD) and skin-graft whether this fusion protein could inhibit alloreactive T cell activation and lead to immunosuppression of activated T cell. Results: In vitro assay, CTLA4Ig fusion protein inhibited immune response in T cell-specific manner: 1) Human CTLA4Ig inhibited allogeneic stimulation in murine MLR; 2) CTLA4Ig prevented the specific killing activity of CTL. In vivo assay, human CTLA4Ig revealed the capacities to induce alloantigen-specific hyporesponsiveness in mouse model: 1) GVHD was efficiently blocked by dose-dependent manner; 2) Clinical score of EAE was significantly decreased compared to nomal control; 3) The time of skin-graft rejection was not different between CTLA4Ig treated and control group. Conclusion: Human CTLA4Ig suppress the T cell-mediated immune response and efficiently inhibit the EAE, GVHD in mouse model. The mechanism of T cell suppression by human CTLA4Ig fusion protein may be originated from the suppression of activity of cytotoxic T cell. Human CTLA4Ig could not suppress the rejection in mouse skin-graft, this finding suggests that other mechanism except the suppression of cytotoxic T cell may exist on the suppression of graft rejection.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.43.1-43.11
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• 2020

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44^hiCD62L^lo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4⁺CD8⁺ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4⁺ T cell activation and proliferation between whole immune cell-specific Cic-null (Cic^f/f;Vav1-Cre) and T cell-specific Cic-null (Cic^f/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4⁺ T cells were more apparent in Cic^f/f;Vav1-Cre mice than in Cic^f/f;Cd4-Cre mice. Cic^f/f;Vav1-Cre CD4⁺ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cic^f/f;Cd4-Cre CD4⁺ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cic^f/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4⁺ T cells than did mixed wild-type and Cic^f/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4⁺ T cells with enhanced T cell activation and proliferative capability.