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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    

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    

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    

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    

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    

免疫细胞在器官移植免疫排斥和免疫耐受中的不同作用 Review

干晓杰, 古鉴, 鞠峥, 吕凌

《工程(英文)》 2022年 第10卷 第3期   页码 44-56 doi: 10.1016/j.eng.2021.03.029

摘要:

器官移植免疫排斥反应是由多种细胞参与的复杂的免疫应答过程,是决定移植成败和患者生存的关键因素。目前大多数器官移植患者采用免疫抑制剂和生物制剂的组合疗法来控制移植器官的免疫排斥反应,然而免疫抑制剂的使用会降低移植患者免疫系统功能,导致严重的并发症,如慢性感染、恶性肿瘤等。因
此,彻底了解器官移植免疫耐受和免疫排斥的相关机制对于开发更好的治疗方案和改善患者预后至关重要。本文对免疫细胞在器官移植免疫排斥和免疫耐受诱导过程中的作用,以及目前针对移植患者处于临床试验阶段的新型细胞治疗进行概述。

关键词: 免疫细胞     固有免疫细胞     适应性免疫细胞     器官移植     免疫耐受    

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    

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.

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    

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    

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    

Toll-like receptors in innate immunity and infectious diseases

Min-Hao WU, Ping ZHANG, Xi HUANG,

《医学前沿(英文)》 2010年 第4卷 第4期   页码 385-393 doi: 10.1007/s11684-010-0600-x

摘要: The protective ability of host defense system is largely dependent on germ-line encoded pattern-recognition receptors (PRRs). These PRRs respond to a variety of exogenous pathogens or endogenous danger signals, by recognizing some highly conserved structures such as pathogen-associated molecular patterns (PAMPs) and danger/damage associated molecular patterns (DAMPs). The most studied PRRs are Toll-like receptors (TLRs). Activation of TLRs triggers production of inflammatory cytokines and type I interferons (IFNs) via myeloid differentiation primary response gene 88 (MyD88)-dependent or-independent signaling respectively, thereby modulating innate and adaptive immunity, as well as inflammatory responses. This review introduces the classification, structure, and specific ligands of TLRs, and focuses on their signal pathways and biological activities, as well as clinical relevance. These studies of TLRs in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including tuberculosis (TB), microbial keratitis, and hepatitis B and C.

关键词: Toll-like receptors     innate immunity     infectious disease     inflammation    

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    

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿(英文)》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要: The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词: antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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    

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

免疫细胞在器官移植免疫排斥和免疫耐受中的不同作用

干晓杰, 古鉴, 鞠峥, 吕凌

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

Toll-like receptors in innate immunity and infectious diseases

Min-Hao WU, Ping ZHANG, Xi HUANG,

期刊论文

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

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

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