• Journal of Physiology & Pathology in Korean Medicine
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• 제22권4호
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• pp.856-862
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• 2008

The purpose of this study was to evaluate the effect of Samsoeum(SSE) on cytokine regulation of mouse T cells. The proliferation of mouse CD4 T cells under the influence of SSE extract was measured. When mouse CD4 T cell were stimulated with anti-CD3 and anti-CD28 in various concentrations of SSE extract, it increased proliferation of CD4 cells by 30% in $50{\mu}g/m{\ell}$ concentration. The proliferation of CD4 cells increased in $100{\mu}g/m{\ell}$ and $200{\mu}g/m{\ell}$. Treatment of CD4+ T cells stimulated by anti-CD3e and anti-CD28 with SSE resulted in reduction of $IFN-{\gamma}$ and IL-4 levels. SSE has dose-dependent inhibitory effect on $IFN-{\gamma}$ and decreased IL-4 by 70% at 50, $200{\mu}g/m{\ell}$. Oral administration of SSE resulted in increase of CD8+ T cell population in Balb/c mice by 8%. CD4+ T cells under Th1/Th2 polarizing conditions for 3 days with SSE resulted in decrease of $IFN-{\gamma}$ level in Th1 cells by 44% and increase of IL-4 level in Th2 cells by 60%. Experimental results of this study show that SSE induces mouse T-cell to transform into Th2, and increases T-cell population and activation.

• Korean Journal of Microbiology
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• 제47권4호
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• pp.342-347
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• 2011

T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

• IMMUNE NETWORK
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• 제10권6호
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• pp.247-249
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• 2010

Foxp3 is a transcript factor for regulatory T cell development. Interestingly, Foxp3-expressing cells were identified in B cells, especially in CD19(+)CD5(+) B cells, while those were not examined in CD19(+)CD5(-) B cells. Foxp3-expressing CD5(+) B cells in this study were identified in human PBMCs and were found to consist of $8.5{\pm}3.5%$ of CD19(+)CD5(+) B cells. CD19(+)CD5(+)Foxp3(+) B cells showed spontaneous apoptosis. Rare CD19(+)CD5(+) Foxp3(+) regulatory B cell (Breg) population was unveiled in human peripheral blood mononuclear cells and suggested as possible regulatory B cells (Breg) as regulatory T cells (Treg). The immunologic and the clinical relevant of Breg needs to be further investigated.

• BMB Reports
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• 제30권6호
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• pp.415-420
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• 1997

Although $CD4^+$ T cell responses to protein-derived antigen have well been understood, the epitopes recognized by hapten-specific $CD4^+$ T cells have not been fully defined. In this study, we characterized the response of a T cell hybridoma (5Di0.1B8) which is specific for a hapten. N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) restricted by MHC class II $I-A^d$. Using three different antigen presenting cells (APCs) expressing $I-A^d$, the role of class II MHC proteins in haptenic antigen presentation and subsequent activation of 5D10.1B8 has been examined. Activation of 5D10.1B8 T cells by HSAB analogs was also performed. Our results show that each APC activated T cells differentially and that interleukin-2 (IL-2) augmented antigen-presenting ability of all the APCs, suggesting that increased expression of class II MHC protein by IL-2 played an important role in HSAB presentation and T cell activation. Finally, early T cell receptor-dependent signals induced by HSAB or its analogs were examined by phosphotyrosine immunoblot analysis, and showed that tyrosine phosphorylation level of a 18-20 kD protein increased upon stimulation.

• Journal of Physiology & Pathology in Korean Medicine
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• 제16권4호
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• pp.801-809
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• 2002

CSBHT is known to improve immunological response in mice and humans. In this study, CSBHT effect was examined in the context of CD4+ T cells' survival and TCR/CD3 induced activation responses. Spleen cells from 8 week BALB/c mice were cultured in CSBHT containing medium without activation for 24, 48 hr. The MTS assay and revealed that CSBHT did not stimulate spleen lymphocytes as mitogen. Spleen lymphocytes were treated with anti-CD3e/anti-CD28 antibodies for 48hr. Flow cytometry revealed that activity of T cell decreased with CSBHT concentration. CD4+ T cells were isolated and cultured ,in CSBHT containing medium for 48 hr. CSBHT did not affect survival of sorted CD4+ T cells without any involvement of APC. In order to evaluate the direct effect of CSBHT on helper T cells's proliferative capacity prior to activation, CD4+ T cells are isolated after 24hr of culture in CSBHT containing medium and activated with and without anti-CD3e/anti-CD28 activation for 48hr. A higher level of CD69 was observed in 1 ㎍/㎖ of CSBHT treatment than control using flow cytometry. But low CD69 expression was observed in 5㎍/㎖ of CSBHT treatment. Expression of mRNA for cytokines in CD4+ T cell revealed that IL-2 expression was increased in 1 ㎍/㎖. The expression of IL-2R α, INF- γ were increased with concentration. On the other hand mRNA of IL-4 was decreased in dose dependent manner. Results suggest that CSBHT may be desirable for CD4+ T cell's activity in immune responses. Further more, CSBHT may relatively activate Th1 and inactivate Th2.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• International Journal of Stem Cells
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• 제15권3호
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• pp.291-300
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• 2022

Background and Objectives: Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail. Methods and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton's jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG₁ and IgG_2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220⁺ GL7⁺) and memory T cells (CD62L⁺ CD44⁺) both in CD4⁺ and CD8⁺ subsets. Similar results were obtained for C57BL/6 mice. Conclusions: hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity.

• Preventive Nutrition and Food Science
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• 제8권1호
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• pp.7-12
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• 2003

This study examined the effect of pine needle distillate (Pinus densiflora Sieb. et Zucc) on the immune system and hematological parameters. C57BL/6 male mice weighing 20 ~21 g were divided into 3 groups and intraperitonially injected with either 200 $\mu$L of saline (control), 50% diluted (P50) or 100% pine needle distillate (P100) once a day for 24 days. At the end of the experiment, the mice were anesthetized by ether and peripheral blood was collected from the femoral artery and the spleen was excised. Spleen weight decreased significantly (p<0.001) in the pine needle groups compared to the control group. The blood was used for a complete blood count and flow cytometrical analysis after immunofluorescence staining. The pine needle distillate dose-dependently decreased the CD4$^{＋}$/CD8 sup ＋/ ratio (p <0.05), and showed a tendency to increase the mean FSC (forward scatter) values of the CD8$^{＋}$T cells, while decrease the values of the CD4$^{＋}$T cells. There were no significant differences in WBC, RBC and platelet counts among the three groups, but hemoglobin and hemoglobin-related parameters and platelet volume increased and red blood cell volumes decreased with the administration of the pine needle distillate. These results suggest that the pine needle distillate may have immunosuppressive effects.

• The Korea Journal of Herbology
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• 제24권1호
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• pp.73-78
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• 2009

Objectives : In this study, we studied the effect of Pinellia Ternata (PT) on regulatory T cells and CD3+CCR3+ Th2 cells number in asthma model mice. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of 0.2 $m\ell$ alum-precipitated Ag containing 100 ${\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks(at a flow rate of 250 L/min, 2.5％ ovalbumin in normal saline) and PT (400, 200 mg/kg) were orally administered 3 times a week for 8 weeks. After C57BL/6 mice were orally given of PT, the percentages, cell numbers, phenotype and function of CD4+CD25+Treg cells were determined by flow cytometry. Results : The cell numbers of CD4+CD25+Treg cell subsets were markedly increased in PT treated mice as reported. However, PT significantly reduced the CD3+CCR3+ Th2 cells in PBMC and lung of mice. Conclusions : These results indicate that PT has a deep inhibitory effect on asthma model mice by increase the number of regulatory T cells, and by reducing CD3+CCR3+ Th2 cells.

• Journal of Yeungnam Medical Science
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• 제14권2호
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• pp.359-369
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• 1997

We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.