• Parasites, Hosts and Diseases
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• v.61 no.2
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• pp.138-146
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• 2023

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1β, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1β was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

• IMMUNE NETWORK
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• v.7 no.4
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• pp.197-202
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• 2007

Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

• Korean Journal of Veterinary Research
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• v.28 no.2
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• pp.227-239
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• 1988

In order to investigate the morphological characteristics of dendritic cells in the mammary gland, the appearance on the clear cells(CLs) or ATPase-positive dendritic cells(APDCs) have been observed by the light microscope. The results obtained were summarized as follows: CLs were observed in the mammary tissues of the experimental animals, such as mice, rats, guinea pigs, rabbits, cats, dogs, pigs, cows and Korean native goats, and these CLs were confirmed as the ATPase-positive cells of typical dendritic appearance(APDCs), The APDCs were distributed in between the secretory epithelial cells, between the secretory epithelial cells and the myoepithelial cells, the basal area of the secretory epithelial cells, the interalveolar and interlobular connective tissues, and in between the epithelial cells of secretory duct. The APDCs were observed more frequently during the middle period of lactation than the other periods, and were irregularly or uniformly distributed according to the location. During the middle period of lactation, there were notable quantitative differences in the APDSs depending on the mammary glands of mice, rats, guinea pigs, rabbits and cats, The most prominent differences were recognized among the mice, guinea pigs and cats. The number of AP DCs per unit area was statistically fewer in the guinea pigs($209.07{\pm}51.75cells/mm^2$) than in the mice($221.00{\pm}50.94cells/mm^2$) and cats($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.05, p<0.05). Among the A/J, DBA/2, C57BL/6 and NIH(GP) mice, the mean densities of APDCs was statistically significantly fewer in the DBA/2($196.65{\pm}43.47cells/mm^2$) than in the C57BL/6($248.40{\pm}41.40cells/mm^2$) and NIH(GP) ($235.98{\pm}55.89cells/mm^2$) (respectively, p<0.0000, p<0.0000), however no significant difference between the C57BL/6 and the NIH(GP) was recognized (p>0.1). Among the F344, SD and W rats, the statistical analysis were confirmed that there were significantly fewer APDCs in the F344($198.72{\pm}47.61cells/mm^2$) than in the SD($227.70{\pm}41.40cells/mm^2$) and W($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.0000, p<0.0001), however no significant difference between the SD and the W was recognized(p>0.1). The mean difference between the inbred and the noninbred counts in the mice was statistically significant (p<0.0001), and the similar result was presented in the rats(p<0.0000).

• Molecules and Cells
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• v.46 no.11
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• pp.688-699
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• 2023

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B₁ exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.171-172
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• 2002

Immune responses to infectious microbes and foreign antigens are regulated by a series of interactions among T cells, B cells, and antigen-presenting cells (APCs) such as macrophages (M$\square$) and dendritic cells (DCs). The inverse relationship between antibody production and cell-mediated immune responses such as delayed type hypersensitivity (DTH) was experimentally manipulated by varying the dose, route of administration, and form of antigen used to immunize animals. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.166.1-166.1
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• 2003

We investigated the effects of bisphenol A (BPA), endocrine disruptor, on the mixed lymphocyte reaction and TNF-$\alpha$ production of antigen presenting cells in mice. Cells from mouse (C57BL/6) bone marrow were cultured with GM-CSF for 8 days and mature dendritic cells (DCs) were prepared. These DCs proliferation in response to Balb/c splenocytes was measured at 72 h of culture with BPA by tritiated thymidine incorporation ([3H]TdR) and [3H]TdR incorporation was determined by scintilation counting. (omitted)

• IMMUNE NETWORK
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• v.20 no.6
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• pp.49.1-49.15
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• 2020

C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5^-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5^-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c⁺ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

• 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)

• Parasites, Hosts and Diseases
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• v.55 no.4
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• pp.375-384
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• 2017

Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis ${\alpha}$-actinin 2, $Tv{\alpha}$-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of $Tv{\alpha}$-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-$Tv{\alpha}$-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or $Tv{\alpha}$-actinin 2 protein. Both T. vaginalis and $rTv{\alpha}$-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, $CD4^+CD25^-$ regulatory T cells (Treg cells) incubated with $rTv{\alpha}$-actinin 2-treated DCs produced high levels of IL-10. These data indicate that $Tv{\alpha}$-actinin 2 modulates immune responses via IL-10 production by Treg cells.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.192-198
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• 2006

Background: Investigating strategy to enhance efficiency of gene transfer via adenovirus is critical to sustain gene expression in targeted cells or tissues to regulate immune responses. However, the use of adenovirus as a gene delivery method has been limited by the native tropism of the virus. In this study, the critical parameter is to improve the efficient binding of viral particles to the plasma membrane prior to cellular uptake. Methods: Human immunodeficiency virus (HIV-1) trans-acting activator of transcription (TAT), a protein transduction domain, was fused to the ectodomain of the coxsackie-adenovirus receptor (CAR). The CAR-TAT protein was produced from a Drosophila Schneider 2 cells (S2) transfected with CAR-TAT genes. The function of CARTAT was analyzed the efficiency of adenoviral gene transfer by flow cytometry, and then immunizing AdVGFP with CAR-TAT was transduced on dendritic cells (DCs). Results: S2 transfectants secreting CAR-TAT fusion protein has been stable over a period of 6 months and its expression was verified by western blot. Addition of CAR-TAT induced higher transduction efficiency for AdVGFP at every MOI tested. When mice were vaccinated with DC of which adenoviral transduction was mediated by CAR-TAT, the number of IFN-${\gamma}$ secreting T-cells was increased as compared with those DCs transduced without CAR-TAT. Conclusion: Our data provide evidence that CAR-TAT fusion protein enhances adenoviral transduction and immunogenecity of transgenes on DCs and may influence on the development of adenoviral-mediated anti-tumor immunotherapy.