• 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.1 no.2
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• pp.95-103
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• 2001

T cells play a central role in the initiation and regulation of the immune response to foreign antigens. Full activation of T cells requires the engagement of T cell receptor complex (TCR) and the binding of a second costimulatory receptor to its ligand expressed on antigen presenting cells (APC). Among the molecules known to provide costimulatory function, CD28 has been the most dominant and potent costimulatory molecule. However, the function of CD28 is becoming more complex due to the recent discovery of its structural homologue, CTLA-4 and ICOS. This review summarizes the biology and physiologic function of each of these receptors, and further focuses on the biochemical mechanism underlying the function of these receptors. Complete understanding of the CD28/CTLA-4/ICOS costimulatory pathway will provide the basis for developing new therapeutic approaches for immunological dieseases.

• Korean Journal of Veterinary Research
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• v.38 no.1
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• pp.91-99
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• 1998

The immunogenetic analysis was performed to characterize the Korean native chickens (KNC) determined by monoclonal antibodies specific to chicken leukocyte differentiation antigens and flow cytometry. A total of 174 chickens including 58 KNC (black, brown and darkbrown colored), 77 foreign breed (Nagoya, White Reghorn, Rhode Island and Cornish) and 39 mixed breed (19 KNC with Nagoya and 20 KNC with Rhode Island) separately growing at Animal Science and Technology Institute were examined. The proportion of cells expressing MHC class II molecule (B-L in chicken) was significantly high in KNC. Proportion of CD4+ T helper cells was also higher in KNC and two mixed breed than that in foreign breed. However, proportion of CD8+ cells and TCR1 + (${\gamma}^{\delta}$ T cell receptor) cells was the lowest among the breed examined. Otherwise, those proportions were significantly high in White leghorn and two mixed breeds with two exclusive subpopulations. The two subpopulations were also typically shown in MHC class $II^+$ cells in KNC and one mixed breed, black-colored KNC with Nagoya. Although genotypic analysis was not pursued to characterize the immunogenetic properties of KNC, difference of phenotypic expression based on leukocyte differentiation molecules could be elucidated in KNC in this study.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.127-132
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• 2009

Background: Toll-like receptors (TLRs) play a fundamental role in innate immunity through their capacity to recognize pathogen-associated molecular patterns. Also, TLRs that are expressed in T cells are reported to function as co-stimulatory receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2 ligand plus TCR-mediated stimulation. Methods: TLR2 expression was analyzed on T cell subsets under naive and alloantigen-primed conditions. We analyzed the effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in vitro when stimulated with soluble anti-CD3 in the presence or absence of synthetic ligand $Pam_3CSK_4$. Results: TLR2 expression on CD8 T cells was induced following activation; this expression was much higher than on CD4 T cells. Thus, the molecule was constitutively expressed on Listeriaspecific memory CD8 T cells. Based on these expression levels, proliferation and survival were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by $Pam_3CSK_4$ compared with those in CD4 T cells. Conclusion: Our data show that TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T cells than for that of CD4 T cells.

• Molecules and Cells
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• v.28 no.2
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• pp.125-130
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• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• Journal of the Korean Physical Society
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• v.73 no.12
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• pp.1908-1917
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• 2018

The binding affinity between the T-cell receptors (TCRs) and antigenic peptides mainly determines immunological recognition. It is not a trivial task that T cells identify the digital sequences of peptide amino acids by simply relying on the integrated binding affinity between TCRs and antigenic peptides. To address this problem, we examine whether the affinity-based discrimination of peptide sequences is learnable and generalizable by artificial neural networks (ANNs) that process the digital experimental amino acid sequence information of receptors and peptides. A pair of TCR and peptide sequences correspond to the input for ANNs, while the success or failure of the immunological recognition correspond to the output. The output is obtained by both theoretical model and experimental data. In either case, we confirmed that ANNs could learn the immunological recognition. We also found that a homogenized encoding of amino acid sequence was more effective for the supervised learning task.

• Journal of Veterinary Clinics
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• v.26 no.5
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• pp.419-422
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• 2009

We performed the PARR (PCR to detect antigen receptor rearrangements) test on DNA isolated from twelve archival canine cytological slides including nine lymphoma, two reactive lymphocytes and one sample from Ehrlichia canis infected dog. As a result, our PCR control gene, $C{\mu}$, was successfully amplified from all of the DNA samples. Six out of nine lymphoma samples showed a clonal rearrangement of immunoglobulin gene whereas three samples did a clonal rearrangement of T cell receptor gamma ($TCR{\gamma}$) gene. However, we observed no visible or clear bands from PCR conducted using our antigen receptor rearrangement primers on DNA from a reactive lymphoid cell proliferation used as a negative control. False-positive amplification in $TCR{\gamma}$ gene was observed only in one sample from E. canis infection. The use of archival cytological specimens demonstrated in this study offers potential advantages for cost-effective specimen acquisition and efficient high-fidelity DNA analysis.

• Molecules and Cells
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• v.39 no.8
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• pp.603-610
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• 2016

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.50-58
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• 2011

Background: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. Methods: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. Results: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. $CD8^+$ T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR $V{\beta}$ CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. Conclusion: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1330-1334
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• 2003

Astragali Radix(AR), one of the strong tonic herbs, is known to improve immunological responses in mice and human. In this study, AR's ai-reinforcing effect was examined in the context of CD4/sup +/ T cells' TCR/CD3 induced activation responses. In order to evaluate the direct effect of AR on helper T cells, CD4/sup +/ T cells are isolated using magnetic bead and their proliferation and CD69 expression in AR treated medium were assessed with anti-CD3/anti-CD28 activation for 48h. CD4 T cells' proliferation was slightly increased but there was little effect on CD69 expression. RT PCR and ELISA equally demonstrated that IL-2 and IL-4 production was increased but IFN-ν was down-regulated. This shows AR ethanol extract favors Th2 cytokine profile under neutral conditions.