• Advances in Traditional Medicine
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• v.4 no.3
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• pp.163-170
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• 2004

The effect of immune activation by Echinacea purpurea was investigated by measuring total immunoglobulin (Ig) G, IgM. and the radioprotective effect of immune activation by Echinacea purpurea was investigated by measuring T lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Echinacea purpurea activated macrophages to stimulate $IFN-{\gamma}$ production in association with the secondary activation of T lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Echinacea purpurea administration activated helper T cells to proliferate. In addition, activated macrophages in association with the secondary T lymphocyte activation increased $IFN-{\gamma}$ production and stimulated proliferation of cytotoxic T cells and suppressor T cells, indicating the activation of cell-mediated immune responses.

• Journal of Microbiology and Biotechnology
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• v.22 no.8
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• pp.1066-1076
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• 2012

Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

• IMMUNE NETWORK
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• v.9 no.2
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• pp.53-57
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• 2009

Engagement of the immunoreceptors initiates signaling cascades resulting in lymphocyte activation and differentiation to effector cells, which are essential for the elimination of pathogens from the body. For the transduction of these immunoreceptor-mediated signals, several linker proteins termed transmembrane adaptor proteins (TRAPs) were shown to be required. TRAPs serve as platforms for the assembly and membrane targeting of the specific signaling proteins. Among seven TRAPs identified so far, LAT and LIME were shown to act as a positive regulator in TCR-mediated signaling pathways. In this review, we will discuss the functions of LAT and LIME in modulating T cell development, activation and differentiation.

• 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.

• BMB Reports
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• v.39 no.4
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• pp.406-411
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• 2006

Signaling lymphocyte activation molecule (SLAM; also known as CD150) is a newly identified cellular receptor for measles virus (MV). The interaction between MV Haemagglutin (MVH) and SLAM is an initial step for MV entry. We have identified several novel SLAM binding sites at residues S429, T436 and H437 of MVH protein and MVH mutants in these residues dramatically decrease the ability to interaction with the cell surface SLAM and fail to co-precipitation with SLAM in vivo as well as malfunction in syncytium formation. At the same time, K58, S59 and H61 of SLAM was also identified to be critical for MVH and SLAM binding. Further, these residues may be useful targets for the development of measles therapy.

• Korean Journal of Biological Psychiatry
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• v.3 no.2
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• pp.170-180
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• 1996

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the passibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen far each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantitfied and the influence of ${\beta}$-amyloid protein($A{\beta}$) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing $A{\beta}$ immunoreactivity was found in the T-sell dependent zone. FACS indicated that around 90% $CD_4(+)$ T-cells and 60% of $CD_8(+)$ T-sell were immunoreactive to $A{\beta}$ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the $A{\beta}$ immunoreactivity an cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted farm of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only law levels in the resting stale. Immunoblot was carried out an the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that $A{\beta}$ band of immature farm under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal $A{\beta}$ specific(4G8) and polyclonal APP antibodies did not inhibit the [$^3H$]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific $A{\beta}$ and polyclonal APP antibody. These results suggest that APP is expressed in T-cell and might be closely associated with the function of T-cells.

• Journal of Ginseng Research
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• v.32 no.3
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• pp.250-256
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• 2008

Red ginseng is a medicinal herb widely used in East-Asia for a long time. Recently there have been a lot of studies about the effect of red ginseng on the immune responses. We investigated the differences between Korean red ginseng and Chinese red ginseng in the lymphocyte proliferation and cytokine production. The rats were divided into 3 groups, KRG(Korean Red Ginseng) group, CRG(Chinese Red Ginseng) group, and the Control group. Experimental groups were administered with Korean and Chinese red ginsengs for three months respectively. Then we obtained the lymphatic cells from spleen and compared the ability of KRG on the lymphocyte proliferation and the cytokine production after mitogen-stimulated culture to CRG. The proliferation of lymphocyte and level of $IL-1{\alpha}$ were significantly increased only in KRG group. There were significant increases in the level of $INF-{\gamma}$ in both KRG and CRG groups. There were no significant differences in the level of IL-2 and $TNF-{\alpha}$. These results indicate that KRG can induce infection-relevant immune responses much faster and higher than CRG. Furthermore, functional activation of CD8+ T-cell may be activated by red ginsengs.

• Proceedings of the Zoological Society Korea Conference
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• 1994.10a
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• pp.260.2-260
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• 1994

No Abstract, See Full Text

• Translational and Clinical Pharmacology
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• v.25 no.2
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• pp.63-66
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• 2017

Allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are reportedly associated with the $HLA-B^{\star}58:01$ genotype. Three patients who developed SCARs after allopurinol administration were subjected to HLA-B genotyping and lymphocyte activation test (LAT) to evaluate genetic risk and to detect the causative agent, respectively. All three patients given allopurinol to treat gout were diagnosed with DRESS syndrome. Symptom onset commenced 7-24 days after drug exposure; the patients took allopurinol (100-200 mg/d) for 2-30 days. HLA-B genotyping was performed using a polymerase chain reaction (PCR)-sequence-based typing (SBT) method. All patients had a single $HLA-B^{\star}58:01$ allele: $HLA-B^{\star}13:02/^{\star}58:01$ (a 63-year-old male), $HLA-B^{\star}48:01/^{\star}58:01$ (a 71-year-old female), and $HLA-B^{\star}44:03/^{\star}58:01$ (a 22-year-old male). Only the last patient yielded a positive LAT result, confirming that allopurinol was the causative agent. These findings suggest that patients with $HLA-B^{\star}58:01$ may develop SCARs upon allopurinol administration. Therefore, HLA-B genotyping could be helpful in preventing serious problems attributable to allopurinol treatment, although PCR-SBT HLA-B genotyping is time consuming. A simple genotyping test is required in practice. LAT may help to identify a causative agent.

• Journal of Life Science
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• v.22 no.3
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• pp.312-317
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• 2012

The time-dependent effects of highly intensive exercise on the hematological properties of leukocytes, as well as $CD4^+$ and $CD8^+$ level changes as T-lymphocyte activation subsets and the cell death of lymphocytes in rats were studied in this research. Twenty, 60, and 120 min of highly intensive exercise was performed daily for 8 weeks. Total leukocyte counts in the blood of rats exercising for 20 min were elevated; they then decreased to less than the level of the control group up to 120 min. The patterns of lymphocyte level changes were directly influenced by exercise duration and the extents of alteration were similar to the total leukocytes counts. The levels of $CD4^+$ and $CD8^+$ in the blood of the exercising rats were not statistically different even when the exercise was continued for 120 min; thus, the exercise did not affect T-lymphocyte activation. Early- and late-stage lymphocyte apoptosis was not affected by the length of exercise, except that late-phase apoptosis was slightly increased at 120 min, suggesting that aging processes for lymphocyte apoptosis might be stimulated at that time. As the exercise time became longer, stimulated necrosis of lymphocytes was observed, so damage in lymphocytes and a potential loss of immunity might be presumed. The current observation suggests that long-term, highly intensive exercise might result in a loss of immunity that could be due to the damage of lymphocytes in terms of both their numbers and inflammation-related functions. The results suggest that under highly intensive exercise conditions, more than 20 min of exercise should not be suggested for health care purposes.