• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.111-129
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• 1998

In order to research the effect of Sipjundaebotang on the immune respons of CD4+ T cell and CD8+ T cell in rats, author have performed this experimental study. Experimental groups are divided into 5 groups(intact, control, sample I, sample II, sample III). Normal group was intact, control group was administrated normal saline 2cc for 5 days, sample I was administrated low concentration of Sipjundaebotang(100/3100pack/ml) 2cc for 5 days, sample II was administrated middle concentration of Sipjundaebotang(500/3100pack/ml) 2cc for 5 days, sample III was administrated high concentration of Sipjundaebotang(2500/3100pack/ml) 2cc for 5 days. WBC, Lymphocyte, CD4+ T cell in the blood, spleen, axillary node and CD8+ T cell in the blood, spleen and axillary node were determined. The results was as follows: 1. WBC count in blood was significantly decrcased in the control, sample I, II, III groups as compared with the normal group. 2. Lymhocyte count in the blood was significantly decreased in the control, sample I, II groups as compared with the normal group. 3. CD4+ T cell count in the blood was significantly increased dose-dependently in the sample I, II, III groups as compared with the normal group. 4. CD4+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. 5. CD4+ T cell count in the axillary node was significantly increased in the sample III group as compared with the normal group, however significantly decreased in the sample I, II groups as compared with the normal group. 6. CD8+ T cell count in the blood was significantly increased in the sample III groups as compared with the normal group. 7. CD8+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. but there was no differences in the sample groups. 8. CD8+ T cell count in the axillary node was decreased in the sample I, II groups as compared with the normal group.

• 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.24 no.1
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• pp.9.1-9.21
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• 2024

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.118-125
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• 2012

CD40-CD40L-mediated help from CD4 T cells is essential to induce primary CD8 T cell responses specific to the non-inflammatory cell-based antigen H60. In this study, using H60 as a model antigen, we generated recombinant vaccinia viruses (rVVs) expressing the H60 CD8 epitope and investigated whether CD4 help was required to activate the CD8 T cell response specific to the virally expressed H60. The immune response after infection with rVVs expressing H60 was similar to that after immunization with H60 congenic splenocytes, with a peak frequency of H60-specific CD8 T cells detected in the blood on day 10 post-infection. A CD8 T cell response specific for virally derived H60 was not induced in CD4-depleted mice, but was in CD40-deficient mice. These results provide insights into the characterization of the CD8 T cell response specifically for antigens originating from cellular sources compared to viral sources.

• Journal of Life Science
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• v.21 no.2
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• pp.316-321
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• 2011

Generation of tryptophan-derived metabolites by indoleamine 2,3-dioxygenase (IDO) is a potent immunoregulatory mechanism in T cell responses. However, the mechanism remains unclear. We showed that 3-hydroxyanthranilic acid (3-HAA), the most potent metabolite, selectively induced apoptosis in activated T cells, but not in resting T cells. This was not associated with cell cycle arrest. We found that TRAIL expression was selectively induced in activated T cells by treatment of 3-HAA. Blockade of the TRAIL: DR4/DR5 pathway significantly inhibited 3-HAA-mediated T cell death. Our data suggest that TRAIL-induced apoptosis is involved in the mechanism of 3-HAA-mediated T cell death.

• Molecules and Cells
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• v.40 no.1
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• pp.24-36
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• 2017

The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by $L^d$ MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for $L^d$ is measurably weaker than that of QL9, but either peptides in the context of $L^d$ interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, $EC_{50}s$ of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for $L^d$. When $EC_{50}s$ for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, $L^d/P2Ca$ dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of $L^d/P2Ca$ with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.

• 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.

• Proceedings of the Korea Contents Association Conference
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• 2008.05a
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• pp.274-280
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• 2008

The study of subjects were 8 persons. The study measured VO2max of each person and substituted METs at exercise intensity of both VO2max 50% and VO2max 70% in accordance with energy consumption formula to set exercise time at energy consumption of both 300kcal and 600kcal. And, the study substituted inclination and rate at exercise intensity that was measured at preliminary test. T, B, NK cell varied depending upon aerobic exercise to have no significant difference of exercise intensity at relative ratio of T, B, NK lymphocyte of all of lymphocytes and to have significant difference of Expenditures Calorie (p<.01) and interaction (p<.05) by T cell and Expenditures Calorie (p<.01) by B cell and Expenditures Calorie (p <.001) and interaction (p<.05) by NK cell.

• Parasites, Hosts and Diseases
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• v.54 no.2
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• pp.147-154
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• 2016

Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns were identified by cell counting with trypan blue under confocal microscopy, and cell cycle changes were investigated by flow cytometry. L6 cells infected with T. gondii showed decreased proliferation compared to uninfected L6 cells and revealed a tendency to stay at S or G2/M cell phase. The treatment of exosomes isolated from T. gondii-infected cells showed attenuation of cell proliferation and slight enhancement of S phase in L6 cells. The cell cycle alteration was not as obvious as reduction of the cell proliferation by the exosome treatment. These changes were transient and disappeared at 48 hr after the exosome treatment. Microarray analysis and web-based tools indicated that various exosomal miRNAs were crucial for the regulation of target genes related to cell proliferation. Collectively, our study demonstrated that the exosomes originating from T. gondii could change the host cell proliferation and alter the host cell cycle.

• Restorative Dentistry and Endodontics
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• v.22 no.1
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• pp.374-387
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• 1997

The purpose of this study was to examine the distribution of lymphocyte populations in normal, reversibly inflamed and irreversibly inflamed human dental pulp tissues using flow cytometry. Flow cytometry, with specific antibody and fluorochrome reagent allows us to know cellular properties of hematolymphoid cells by measuring fluorescence of stained cells. Before extirpation of pulps in routine endodontic treatment, the clinical diagnosis were performed by symptom. The extirpated pulp tissues were divided into normal pulp group (N=5), reversible pulpit is group(N=10) and irreversible pulpitis group(N=7). The specimen was placed into RPMI 1640 medium, minced into small pieces, and then digested in medium with collagenase. The cell suspension was resuspended in PBS for monoclonal antibody staining of T lymhocytes(CD3+), B lymphocytes (CD19+), T helper cell (CD4+) and T supressor cell (CD8+). The percentages of cells were counted by FACStar(BD) flow cytometer. Following results were obtained; 1. In the most normal and inflamed pulps, the percentages of T lymphocyte, B lymphocytes, T helper cell and T suppressor/cytotoxic cell were less than 1 % in total counted pulpal cells. 2. The higher percentages of T, B, T helper and T suppressor cells were observed in irreversible pulpitis group as compared with the normal pulp and reversible pulpitis group but the differences between groups were not statistically significant (p>0.05). 3. The percentages of T helper cells (CD4 + cells) were greater than that of T suppressor/cytotoxic cells (CD8 + cells) in the inflamed pulps.