• Proceedings of the PSK Conference
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• 2002.10a
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• pp.307.2-308
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• 2002

Acharan sulfate. a new glycosaminoglycan(GAG) isolated from the giant African snail Achatina fulica. was shown to have antitumor activity in vivo. To elucidate the mechanisms for the antitumor activity. we examined its impact on professional antigen presenting cells such as macrophages and dendritic cells (DCs). Acharan sulfate stimulated cytokine production (TNF-a and IL -1b). nitric oxide release. and morphological changes in a dose dependent manner on a macrophage cell Line Raw 264.7 cells. The differentiation-inducing activity of acharan sulfate was examined on immature DCs. Immature DCs were generated from mouse bone marrow (BM) cells by culturing with GM-CSF and IL-4, and then stimulated with acharan sulfate. The resultant DCs were then examined for funcional and phenotypic properties. It was found that acharan sulfate could induce functional maturation of immature DCs as determined by increased allogenic mixed lymphocyte reaction (MLR) and IL-12 production. Phenotypic. analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2 and CD40 also confirmed that acharan sulfate could induce maturation of immature DCs. These results suggest that that the antitumor activity of acharan sulfate is at least in part due to activation adn induction of differentiation of professinal antigen presenting cells. (omitted)

• IMMUNE NETWORK
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• v.13 no.5
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• pp.184-193
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• 2013

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.44-51
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• 2016

Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.218-221
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• 2013

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although ${\alpha}$-galactosylceramide (${\alpha}$-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-${\gamma}$ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.

• Journal of Microbiology
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• v.33 no.4
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• pp.355-362
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• 1995

Induction of antibody production in C3H/He mice by bacterial infection is regulated through the processing exerted by antigen presenting cells. From the studies with Psudomonas aeruginosa, Salmonella typhimurium, and Micrococcus luteu, lipopolysaccharides (LPS) in Gram negative bacteria, which are known to be T-cell independent B cell mitogen, seem to be the major factor stimulating immune responses via activation of macrophages. Activation of macrophage, however, does not seem to correlate with antibody production. M. luteus was easily eliminatd by activated macrophages, while the processed antigens were immediately releasedd into culture medium before presentation. Nevertheless, antigens from Gram positive bacteria, Staphylococcus aureus and Bacillus subtilis, were very very active in chemotaxis and activation of periotoneal macrophages as well as in antien presnetation, while the very nature of the antigens is not yet clearly understood.

• Archives of Reconstructive Microsurgery
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• v.21 no.1
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• pp.34-40
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• 2012

Prevention of acute rejection in composite tissue allotransplantation without continuous immunosuppression lacks reports in worldwide literature. Recently dendritic cells (DC) gained considerble attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effect of alloantigen-pulsed dendritic cells in induction of survival in a rat hindlimb allograft. We performed hindlimb allotransplantation between donor Sprague-Dawley and recipient Fischer344 rats. Recipient derived dendritic cells were harvested from rat whole blood and cultured with anti-inflammatory cytokine IL-10. Then donor-specific alloantigen pulsed dendritic cells were reinjected into subcutaneous tissue before limb transplantation. Groups: I) untreated (n=6), II) DC injected (n=6), III) Immunosuppressant (FK-506, 2 mg/Kg) injected (n=6), IV) DC and immunouppressant injected (n=6). Graft appearance challenges were assessed postoperatively. Observation of graft appearance, H-E staning, immunohistochemical (IHC) study, and confocal immunofluoreiscece were performed postoperatively. Donor antigen pulsed host dendritic cell combined with short-term immunosuppression showed minimal mononuclear cell infiltration, regulator T cell presence, and could prolong limb allograft survival.

• BMB Reports
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• v.48 no.7
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• pp.369-370
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• 2015

Actin dynamics is critical for the formation and sustainment of the immunological synapse (IS) during T cell interaction with antigen-presenting cells (APC). Thus, many actin regulating proteins are involved in spatial and temporal actin remodeling at the IS. However, little is known whether or how actin stabilizing protein controls IS and the consequent T cell functions. TAGLN2 − an actin-binding protein predominantly expressed in T cells − displays a novel function to stabilize cortical F-actin, thereby augmenting F-actin contents at the IS, and acquiring leukocyte function-associated antigen-1 activation following T cell activation. TAGLN2 also competes with cofilin to protect F-actin in vitro and in vivo. During cytotoxic T cell interaction with cancer cells, the expression level of TAGLN2 at the IS correlates with the T cell adhesion to target cancer cells and production of lytic granules such as granzyme B and perforin, thus expressing cytotoxic T cell function. These findings identify a novel function for TAGLN2 as an actin stabilizing protein that is essential for stable immunological synapse formation, thereby regulating T cell immunity. [BMB Reports 2015; 48(7): 369-370]

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.471-479
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• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.122-135
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• 2018

Listeriolysin O (LLO), one of the most immunogenic proteins of Listeria monocytogenes and its main virulence factor, mediates bacterial escape from the phagosome of the infected cell. Thus, its expression in a nonpathogenic bacterial host may enable effective delivery of heterologous antigens to the host cell cytosol and lead to their processing predominantly through the cytosolic MHC class I presentation pathway. The aim of this project was to characterize the delivery of a model antigen, chicken egg ovalbumin (OVA), to the cytosol of dendritic cells by recombinant Bacillus subtilis vegetative cells expressing LLO. Our work indicated that LLO produced by non-sporulating vegetative bacteria was able to support OVA epitope presentation by MHC I molecules on the surface of antigen presenting cells and consequently influence OVA-specific cytotoxic T cell activation. Additionally, it was proven that the genetic context of the epitope sequence is of great importance, as only the native full-sequence OVA fused to the N-terminal fragment of LLO was sufficient for effective epitope delivery and activation of $CD8^+$ lymphocytes. These results demonstrate the necessity for further verification of the fusion antigen potency of enhancing the MHC I presentation, and they prove that LLO-producing B. subtilis may represent a novel and attractive candidate for a vaccine vector.

• IMMUNE NETWORK
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• v.10 no.3
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• pp.92-98
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• 2010

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.