• IMMUNE NETWORK
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• 제23권2호
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• pp.17.1-17.16
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• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• Journal of Periodontal and Implant Science
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• 제33권4호
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• pp.543-553
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• 2003

Due to considerably high degree of sequence homology between bacterial and human heat shock proteins(hsp), it has been widely thought that this protein might be involved in autoimmune disease mechanisms in humans. To elucidate how stress proteins contribute in the immunopathogenesis of periodontitis, the present study was performed to evaluate the T cell immune responses specific to Porphyromonas gingivalis (P. gingivalis) heat shock protein (hsp)60 and T-cell epitope specificities for P. gingivalis hsp60 in periodontitis. Anti-P. gingivalis IgG antibody titers were elevated in all patients. We could establish P. gingivalis hsp-specific T cell ines from the peripheral blood of peridontitis, a mixture of $CD4^+$ and $CD8^+$ cells. Of 108 overlapping synthetic peptides spanning whole P. gingivalis hsp60 moleculc, ten peptides with cpitopes specifities for T-cell were showed. Interestingly, ten epitopes were also identified as T-cell epitopes in the present study as well as B-cell epitopes in peridontitis. Therefore, all the ten representative epitopes were designated as common T-and B-cell epitopes for peridontitis. It is critical in developing a peptide vaccine strategy for potential prevention of periodontitis. It was concluded that P. gingivalis hsp60 might be involved in the immunoregulatory process of periodontitis with heat shock protein specificities.

• 생약학회지
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• 제35권4호통권139호
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• pp.330-337
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• 2004

Based on the traditional application of Carthamus tinctorious L. (CF) as a component of Korean medicinal decoctions, in the present study, we investigated in vitro an immunomodulatory activity of water extract of CF(WECF). Water extract of CF significantly increased the in vitro proliferative responses of spleen cells (SPC). However, addition of WECF during anti-CD3 activation resulted in a significant decrease in SPC proliferation. Flow cytometric analysis showed that WECF addition chanced T and B cell frequencies in anti-CD3-activated spleen cell populations. Using purified cells, it was revealed that WECF is mitogenic to B cells but rather inhibitory to T cell Proliferation. Upon anti-CD3 stimulation, high concentration (1 mg/ml) of WECF significantly inhibited T cell proliferation until day 2 of stimulation. At day 3, anti-CD3-activated cells exposed to WECF recovered their proliferation to the level comparable to control. Although B cell proliferation was also inhibited in proliferation at day 1, it recovered sooner and then was rather augmented by WECF at day 3. These data indicate that WECF down-regulates lymphocyte proliferation at early phase of activation but T cells are more vulnerable than B cells to WECF, However, CD4+ and CD8+ T cells did not differ in WECF-mediated immunotoxicity. Data of propidium iodide (PI) staining showed that WECF accelerates activated T cell, but not B cell, apoptosis and WECF concurrently inhibited cytokine production of activated T cells. Taken together, WECF exhibits B cell mitogenic activity and differential toxicity more pronounced to T cells, suggesting a possible in vivo application of WECF for specific control of T cells without alteration of B cell activity.

• IMMUNE NETWORK
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• 제8권4호
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• pp.107-123
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• 2008

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

• Clinical and Experimental Reproductive Medicine
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• 제36권3호
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• pp.151-162
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• 2009

착상, 태반생성 및 임신 유지 등 생식과정에서 semi-allograft인 배아 및 태아가 생존하기 위해서는 모체 면역계의 면역관용이 요구된다. 면역관용은 분자 생물학적으로 염증반응과 항염증반응의 적절한 균형을 유지하는 인식되고 있으며, 생식과정에서 모체 면역계의 T 림프구, 자연살해세포, 수지상 세포, 대식세포 등 여러 면역세포의 유기적인 협조하에 이루어진다. 면역세포들은 특정 항원 및 사이토카인의 자극에 따라 정반대의 성질을 가진 사이토카인을 생산, 분비할 수 있는 특성을 가지고 있어 각각을 염증성 또는 항염증성 면역세포로 명확히 구분할 수 없으며 면역세포의 이러한 특성에 의해 생산 및 분비되는 사이토카인의 종류에 따라 Th0 형 (Th 0 cell, Tc 0 cell, NK 0 cell), Th1형 (Th 1 cell, Tc 1 cell, NK 1 cell), Th2 형 (Th 2 cell, Tc 2 cell, NK 2 cell), Th3 형 세포 (Th 3 cell, Tc 3 cell, NK 3 cell)로 분류하기도 한다. 즉, 착상 시기에 혈관신생 및 영양막의 자궁 내 침투를 위한 적절한 염증성 사이토카인(inflammatory cytokine)의 분비 및 임신의 지속을 위한 항염증성 (anti-inflammatory) 사이토카인의 분비 등 생식과정에서 수반되는 염증성과 항염증성 면역반응의 적절한 균형을 유지하는 기전은 특정 면역세포만의 작용으로 결론 지을 수 없으며 면역 세포간 network의 산물이라 할 수 있다 (Figure 5). 면역세포 중 최근 그 존재가 알려진 면역조절 T림프구 (T reg cell)는 여러 연구자들에 의해 면역관용에 관여함이 일관되게 보고되고 있어 자궁 내모체-태아간 접촉면에서 면역세포들 간의 network에 중추적인 역할을 할 것으로 인식되고 있으나 작용기전으로 제시되고 있는 가설들을 뒷받침 할 만한 객관적인 연구가 필요한 실정이다. 본 고찰에서는 착상과 임신 유지 등 생식과정에 수반되는 면역세포 및 그 세포들의 작용기전중 T 림프구의 역할에 중점을 두고 그 분류 및 기능에 대해 정리해 보았다. 결론적으로 착상과 임신의 유지 등 생식과정에서 T 림프구는 면역관용과 거부에 적극적으로 작용하며 착상부전, 습관성유산 등 면역학적 병인이 유사한 생식장애 (poor reproductive performance)들의 발병에 중요한 역할을 하는 것은 의심할 여지가 없다. 하지만 향후 T 림프구 및 그와 연관된 면역세포들의 작용에 대한 확실한 분자학적 규명이 요구된다.

• 약학회지
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• 제38권6호
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• pp.715-720
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• 1994

${\alpha}2-macroglobulin$ $({\alpha}2-M)$ has been shown to have a variety of activities. One of those activities is the suppression of immune response. Characterization of the immunosuppressive factor secreted by a T cell hybridoma showed that ${\alpha}2-M$ was produced and secreted from the T cell hybridoma. ${\alpha}2-M$ was produced abundantly from the T cell hybridoma when cultured as ascites. The isolation and identification of the ${\alpha}2-M$ were studied using affinity chromatography and N-terminal amino acid sequencing. The extended observations were that the ${\alpha}2-M$ produced by the T cell hybridoma suppresses mixed lymphocyte reaction.

• 대한두경부종양학회지
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• 제33권1호
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• pp.7-13
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• 2017

Despite improved treatment outcomes of locally advanced disease over the last 2 decades, the survival of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains dismal. There is a clear need for development of novel therapeutic strategies for recurrent and/or metastatic HNSCC. Recent advances in understanding tumor immunology have been directly and rapidly translated into clinical success of T cell-directed immunotherapeutic approach in the treatment of several types of solid cancers. Among them, impact of immune checkpoint inhibition using neutralizing antibodies is the most striking. A variety of immunotherapeutic strategies targeting T cells have been also studied in HNSCC, especially in recurrent and/or metastatic setting even with significant survival benefit. The present article reviews the basic concept of T cell-directed immunotherapy and the current status of such approaches in the treatment of HNSCC.

• Molecules and Cells
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• 제41권8호
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• pp.717-723
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• 2018

Chimeric antigen receptor (CAR) T-cell therapy, an emerging immunotherapy, has demonstrated promising clinical results in hematological malignancies including B-cell malignancies. However, accessibility to this transformative medicine is highly limited due to the complex process of manufacturing, limited options for target antigens, and insufficient anti-tumor responses against solid tumors. Advances in gene-editing technologies, such as the development of Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), have provided novel engineering strategies to address these limitations. Development of next-generation CAR-T cells using gene-editing technologies would enhance the therapeutic potential of CAR-T cell treatment for both hematologic and solid tumors. Here we summarize the unmet medical needs of current CAR-T cell therapies and gene-editing strategies to resolve these challenges as well as safety concerns of gene-edited CAR-T therapies.

• IMMUNE NETWORK
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• 제23권2호
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• pp.12.1-12.17
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• 2023

Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4⁺ T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4⁺ T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.

• IMMUNE NETWORK
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• 제23권1호
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• pp.8.1-8.13
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• 2023

CD8⁺ T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8⁺ T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8⁺ T cells have been found to express activating or inhibitory NK receptors. CD8⁺ T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8⁺ T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8⁺ T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.