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Innate and adaptive T cells in influenza disease

null

《医学前沿（英文）》 2018年 第12卷 第1期   页码 34-47 doi: 10.1007/s11684-017-0606-8

摘要：

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza     innate T cells     CD4+ and CD8+ T cells     vaccination    

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γδ T cells in liver diseases

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells     liver infection     non-alcoholic fatty liver disease     autoimmune hepatitis     liver fibrosis and cirrhosis     liver cancer     liver regeneration    

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High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

《医学前沿（英文）》 2019年 第13卷 第1期   页码 69-82 doi: 10.1007/s11684-018-0677-1

摘要：

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-g and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.

关键词： cytokine-activated T cells     high-affinity T cell receptor     cancer immunotherapy     TCR-CAT    

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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

《医学前沿（英文）》 2020年 第14卷 第6期   页码 726-745 doi: 10.1007/s11684-020-0746-0

摘要： Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词： CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

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调节性T细胞及其在抗肿瘤免疫疗法中的临床应用 Review

解丰, 梁瑞, 李丹, 李斌

《工程（英文）》 2019年 第5卷 第1期   页码 132-139 doi: 10.1016/j.eng.2018.12.002

摘要： 调节性T 细胞（Treg）是对维持宿主免疫稳态起重要作用的抑制性CD4+ T 细胞的一个亚群。调节性T 细胞缺陷可引起严重的自身免疫、过敏和自身炎症等疾病。调节性T 细胞通常富集在肿瘤微环境中，而大量免疫抑制调节性T细胞往往表明预后较差。因此，人们对调节性T 细胞的功能及其在抗肿瘤免疫疗法中的临床应用再次产生了兴趣。越来越多的策略关注调节性T 细胞的消耗，这在抗肿瘤免疫方面似乎有效。预计调节性T 细胞靶向策略与其他疗法（如嵌合抗原受体T 细胞疗法或免疫检查点阻断）联用将为提高抗肿瘤疗效带来重大机遇。

关键词： 调节性T细胞     癌症     免疫疗法    

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CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

《医学前沿（英文）》 2021年 第15卷 第6期   页码 783-804 doi: 10.1007/s11684-021-0904-z

摘要： The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

关键词： CAR T cells     hematological malignancies     review    

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Changes of phenotype and function of human CD4 CD25 T cells induced by transfection of Foxp3

WU Kui, BI Yutian, WANG Yaoli, WANG Changzheng

《医学前沿（英文）》 2008年 第2卷 第4期   页码 366-369 doi: 10.1007/s11684-008-0070-6

摘要： The aim of this paper is to explore the effects of transfection of Foxp3 gene on the phenotype and function of naive CD4 T cells. The pMSCV-Foxp3 retroviral vector encoding Foxp3 gene was transduced into the PT67 packaging cell line. Virus-containing supernatant was applied to differentiate CD4CD25 T cells. The resulting cells were sorted with flow cytometry. The expressions of CD25, CD127, CTLA-4 and the proliferation of transfected T cells were examined. The effect of transfected CD4 T cells on the proliferation and cytokine production of CD4CD25 T cells was examined. Foxp3-gene transfected CD4 T cells could express Foxp3 and transfection of Foxp3 gene up-regulated the expressions of CD25 and CTLA-4, but down-regulated CD127 expression. After transfection, the proliferation of CD4 T cells was eliminated. Transfected T cells inhibited the proliferation of CD4CD25 T cells. CD4CD25 T cells acquired a regulatory phenotype and function after it was transduced with the Foxp3 gene. This suggested a key role of Foxp3 in the generation of CD4CD25 regulatory T cells.
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Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 374-386 doi: 10.1007/s11684-018-0652-x

摘要：

A family of transcription factors known as Id proteins, or inhibitor of DNA binding and differentiation, is capable of regulating cell proliferation, survival and differentiation, and is often upregulated in multiple types of tumors. Due to their ability to promote self-renewal, Id proteins have been considered as oncogenes, and potential therapeutic targets in cancer models. On the contrary, certain Id proteins are reported to act as tumor suppressors in the development of Burkitt’s lymphoma in humans, and hepatosplenic and innate-like T cell lymphomas in mice. The contexts and mechanisms by which Id proteins can serve in such contradictory roles to determine tumor outcomes are still not well understood. In this review, we explore the roles of Id proteins in lymphocyte development and tumorigenesis, particularly with respect to inhibition of their canonical DNA binding partners known as E proteins. Transcriptional regulation by E proteins, and their antagonism by Id proteins, act as gatekeepers to ensure appropriate lymphocyte development at key checkpoints. We re-examine the derailment of these regulatory mechanisms in lymphocytes that facilitate tumor development. These mechanistic insights can allow better appreciation of the context-dependent roles of Id proteins in cancers and improve considerations for therapy.

关键词： Id proteins     lymphoma     leukemia     T cells     B cells     tumor suppressor     oncogene    

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Th17 Cells in autoimmune diseases

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 10-19 doi: 10.1007/s11684-015-0388-9

摘要：

Th17 cells are a new subset of CD4+ T cells involved in the clearance of extracellular pathogens and fungi. Accumulating evidence suggests that Th17 cells and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sj?gren’s syndrome, inflammatory bowel disease, and multiple sclerosis.

关键词： IL-17     Th17 cells     RORγt     autoimmune diseases     posttranslational modification     inhibitors    

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NKT cells in liver diseases

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells     hepatitis B virus and hepatitis C virus infection     autoimmune liver diseases     alcoholic liver disease     nonalcoholic fatty liver disease     hepatocellular carcinoma    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

《医学前沿（英文）》 2022年 第16卷 第3期   页码 322-338 doi: 10.1007/s11684-021-0901-2

摘要： Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells

《医学前沿（英文）》 doi: 10.1007/s11684-023-1010-1

摘要： Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

关键词： exosomes induce activation     impair function CD19     exosomal CD19 antigen    

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Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation

LU Ling, ZHANG Feng, PU Liyong, YAO Aihua, YU Yue, SUN Beicheng, LI Guoqiang, WANG Xuehao

《医学前沿（英文）》 2007年 第1卷 第4期   页码 373-376 doi: 10.1007/s11684-007-0072-9

摘要： The biological features of intrahepatic CD4CD25 T regulatory cells in the naturally tolerance of rat liver transplantation were explored. Orthotopic liver transplantation was performed in two allogeneic rat strain combinations, one with fatal immunosuppression despite a complete major histo compatibility complex mismatch. The subjects were divided into three groups according to different donors and recipients [Tolerance group: LEW-to-DA; Rejection group: DA-to-LEW; Syngegnic group (control group): DA-to-DA]. The proportion of intrahepatic CD4CD25 T cells from three groups was determined by flow cytometry (FCM) in different time. The intrahepaitc CD4CD25 T cells were isolated by magnetic activated cell sorting (MACS) method and iden tified by FCM. The Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). And their suppression on the proliferation of CD4CD25 T effector cells was analyzed by cell proliferation assay . Beginning immediately after transplantation, the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection group. The proportion of Treg cells declined after day 5, and such reduction was more dramatic in the Rejection group than in the Tolerance group. Animals in the Tolerance group showed a second increase in the proportion after day 14. Intrahepatic CD4CD25 T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte reaction. The purity of CD4CD25 T cells sorted by MACS was 86%–93%. The CD4CD25 T cells could specifically express the Foxp3 gene compared with CD4CD25 T cells. , the spleen cells from LEW rats can irritate the proliferation of CD4CD25 T cells more obviously than the syngegnic spleen cells. CD4CD25 Tr cells could suppress the proliferation of CD4CD25 T cells, but the inhibition was reversed by exogenous IL-2 (200 U/mL). The CD4CD25 T regulatory cells specifically express the Foxp3 gene, which may play an important role in the induction of liver transplantation tolerance by suppressing the reaction of effective T cells.

关键词： magnetic     LEW-to-DA     effector     MACS     cytometry    

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Advances in immunopathogenesis of adult immune thrombocytopenia

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 418-424 doi: 10.1007/s11684-013-0297-8

摘要：

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

关键词： primary immune thrombocytopenia     B lymphocytes     T lymphocytes     antigen-presenting cells     cytokines    

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Performance enhancement of partially shaded solar PV array using novel shade dispersion technique

Namani RAKESH,T. Venkata MADHAVARAM

《能源前沿（英文）》 2016年 第10卷 第2期   页码 227-239 doi: 10.1007/s11708-016-0405-y

摘要： Solar photo voltaic array (SPVA) generates a smaller amount of power than the standard rating of the panel due to the partial shading effect. Since the modules of the arrays receive different solar irradiations, the P-V characteristics of photovoltaic (PV) arrays contain multiple peaks or local peaks. This paper presents an innovative method (magic square) in order to increase the generated power by configuring the modules of a shaded photovoltaic array. In this approach, the physical location of the modules in the total cross tied (TCT) connected in the solar PV array is rearranged based on the magic square arrangement pattern. This connection is done without altering any electrical configurations of the modules in the PV array. This method can distribute the shading effect over the entire PV array, without concentrating on any row of modules and can achieve global peaks. For different types of shading patterns, the output power of the solar PV array with the proposed magic square configuration is compared with the traditional configurations and the performance is calculated. This paper presents a new reconfiguration technique for solar PV arrays, which increases the PV power under different shading conditions. The proposed technique facilitates the distribution of the effect of shading over the entire array, thereby, reducing the mismatch losses caused by partial shading. The theoretical calculations are tested through simulations in Matlab/Simulink to validate the results. A comparison of power loss for different types of topologies under different types of shading patterns for a 4 × 4 array is also explained.

关键词： photovoltaic cells     mismatch loss     shading patterns     partial shading     magic square     power enhancement     global peaks and total cross tied (TCT)    

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标题 作者 时间 类型 操作

Innate and adaptive T cells in influenza disease

null

期刊论文

γδ T cells in liver diseases

null

期刊论文

High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells

Synat Kang, Yanyan Li, Yifeng Bao, Yi Li

期刊论文

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han

期刊论文

调节性T细胞及其在抗肿瘤免疫疗法中的临床应用

解丰, 梁瑞, 李丹, 李斌

期刊论文

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

期刊论文

Changes of phenotype and function of human CD4 CD25 T cells induced by transfection of Foxp3

WU Kui, BI Yutian, WANG Yaoli, WANG Changzheng

期刊论文

Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

null

期刊论文

Th17 Cells in autoimmune diseases

null

期刊论文

NKT cells in liver diseases

null

期刊论文

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a

期刊论文

exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells

期刊论文

Biological features of intrahepatic CD4+CD25+ T cells in the naturally tolerance of rat liver transplantation

LU Ling, ZHANG Feng, PU Liyong, YAO Aihua, YU Yue, SUN Beicheng, LI Guoqiang, WANG Xuehao

期刊论文

Advances in immunopathogenesis of adult immune thrombocytopenia

null

期刊论文

Performance enhancement of partially shaded solar PV array using novel shade dispersion technique

Namani RAKESH,T. Venkata MADHAVARAM

期刊论文