髓源性抑制细胞诱导调节性T细胞产生的机制

髓源性抑制细胞(MDSC)是一群具有免疫抑制功能的未成熟细胞,通过抑制效应T细胞和自然杀伤(NK)细胞等抗肿瘤免疫细胞的功能介导肿瘤免疫逃逸。调节性T细胞(Treg)则在维持自身免疫稳态、控制移植排斥反应中发挥着非常重要的作用,但肿瘤微环境中的Treg却能够减弱机体的抗肿瘤免疫,而且肿瘤抗原和相关细胞因子对Treg的募集、扩增以及诱导产生有重要作用。肿瘤发生时,MDSC对Treg具有正向调控作用,抑制机体正常的抗肿瘤免疫。本文就MDSC促进Treg产生的机制进行综述,以进一步了解MDSC抗肿瘤免疫的机制,为肿瘤的免疫治疗提供新视角。     

调节性T细胞的分化和作用机制研究进展

调节性T细胞(Treg)是一类增殖能力较低,发挥多种免疫抑制功能的T细胞亚群,在维持机体自身的免疫稳态中有着不可忽视的作用,Treg分化或功能异常均能够引发自身免疫性疾病,并与器官移植后的急性免疫排斥反应及肿瘤免疫有关。对Treg生物学特征、数量及功能调控机制的全面了解有助于为临床提供新的治疗思路方法。转录因子Foxp3对于Treg的分化、发育及成熟后的功能维持具有关键性作用。其他多种分子参与Treg的产生、分化及免疫抑制功能。本文总结了Treg的分子标志、分化及作用机制等方面的研究进展。     

调节性T细胞在变应性鼻炎免疫应答中的作用

调节性T(Treg)细胞是CD4+T细胞的一个小而关键的亚群，具有维持免疫稳态的作用，诸多研究已证明Treg在过敏性气道疾病中具有巨大的治疗潜力，在免疫抑制和炎症气道的恢复中起至关重要的作用。在变应性鼻炎（AR）中，Treg可抑制第2组先天淋巴细胞、辅助性T细胞、肥大细胞、树突状细胞、嗜酸性粒细胞和B细胞，从而维持耐受性机制。本综述回顾总结了目前关于Treg在AR中如何调节过敏原引发的免疫应答和维持耐受性机制，对充分利用Treg生物学知识为临床防治AR提供重要参考。     

Th17/Treg细胞平衡在类风湿关节炎发病机制中的研究进展

类风湿关节炎是一种自身免疫性疾病, 具体发病机制不明。辅助性T细胞(helper T cells, Th)17/调节性T细胞(regulatory T cells, Treg)平衡在类风湿关节炎发病中的作用越来越受到重视。Th17细胞及其分泌的细胞因子具有促炎作用, Treg细胞及其分泌的细胞因子具有抑炎作用。Th17细胞增多、Treg细胞减少能够导致关节软骨和骨质的破坏, 引发类风湿关节炎;而调节Th17/Treg细胞平衡能治疗类风湿关节炎。文章就Th17/Treg细胞平衡在类风湿关节炎发病中的作用作一综述。     

c-Maf参与调节性T细胞特化的研究进展

调节性T细胞(regulatory T cell,Treg)在抑制免疫方面具有独特的作用,是宿主维持机体免疫稳态的主要细胞。近年来研究发现,Treg细胞可继续分化为多种亚型,在不同的组织环境和免疫应答中会适应性表现辅助性T细胞(helper T lymphocytes,Th)的特殊表型,表达与Th相关的转录因子,发挥独特的功能特性。肌腱膜纤维肉瘤原癌基因转录因子(c-musculoaponeurotic-fibrosarcoma,c-Maf)在Treg细胞的适应性分化过程有着重要作用。本文就c-Maf在Treg细胞中的特化作用做一简要综述,其中主要涉及表达核激素受体视黄酸受体相关孤儿受体γt(receptor-related orphan receptorγt,RORγt)Treg细胞和表达B细胞淋巴瘤蛋白6(B-cell lymphoma 6,Bcl-6)的滤泡调节性T细胞(follicular regulatory T cell,Tfr)的形成,以进一步讨论Treg细胞介导的免疫机制。     

调节性T细胞在免疫性肾病中的作用及临床应用研究进展

CD4~+CD25~+调节性T细胞(regulatory T cell,Treg)是一类具有免疫抑制效应的T细胞亚群,与机体免疫稳态维持和自身免疫性疾病的发生发展密切相关。由于其独特的生物学功能,Treg细胞已成为自身免疫性疾病的发生、转归和治疗等研究上的热点和难点。本文关注Treg细胞在人类自身免疫性肾病(如狼疮性肾炎、Goodpasture综合征、抗中性粒细胞胞浆抗体相关性血管炎)及啮齿类动物自身免疫性肾病模型中的作用及致病机制,并对Treg细胞在免疫治疗中的潜在临床价值加以探讨。     

新型调节性T细胞CD4~+LAP~+ Treg与疾病的研究进展

调节性T细胞(Treg)是体内存在的一类抑制免疫应答的T细胞亚群,分为天然调节性T细胞(CD4+CD25+Treg)和诱导型调节性T细胞(iTreg),通过细胞-细胞互相接触、分泌细胞因子(IL-10、TGF-β1)等途径抑制B细胞、效应性T细胞的增殖、活化和免疫效应,在抑制自身免疫性疾病发展、移植耐受、肿瘤免疫逃逸等方面发挥重要作用。新的调节性T细胞亚群:CD4+LAP+调节性T细胞(CD4+LAP+Treg),已经被证实在多种动物模型中发挥保护作用,可能是Treg发挥免疫抑制功能关键细胞之一,目前已引起国内外学者的关注。本文对CD4+LAP+Treg的发现及其与疾病关系的研究进展进行综述。     

调节性T细胞促进胃癌发生的研究进展

胃癌(GC)发病因素和机制复杂,GC和机体免疫系统中的调节性T细胞(Treg)密切相关。Treg是一群具有免疫抑制功能的细胞,在维持机体免疫稳态中有重要调节功能,Treg在肿瘤中的作用已成为研究热点。GC患者体内Treg上调,从而抑制机体的抗肿瘤免疫。因此,Treg参与GC的发生发展过程,针对Treg的免疫疗法对于治疗GC具有广阔前景。本文着重就Treg促进GC的作用以及Treg作用机制的研究进展进行综述。     

成纤维样滑膜细胞通过IL-6下调类风湿关节炎患者外周血Treg北大核心CSCD

类风湿关节炎（ rheumatoid arthritis, RA）是以关节组织慢性炎症性病变为主的自身免疫性疾病,成纤维样滑膜细胞（ fibroblast-like synoviocytes, FLS）异常活化是RA发病的重要机制之一,通过释放大量炎症因子、募集其他炎性细胞等方式加重关节侵蚀破坏. 调节性T细胞（ regulatory T cell, Treg）是具有免疫负调节功能的T细胞亚群. 我们推测FLS在RA炎症环境中分泌的炎症因子可能会影响RA患者外周血Treg的比例,本研究旨在阐明RA-FLS对Treg细胞是否具有免疫调控作用及可能的作用途径.     

调节性T细胞与肝细胞肝癌免疫的研究进展

调节性T细胞（Treg）是一类具有独特免疫调节功能的T细胞亚群,可通过多种方式抑制肿瘤免疫,在肿瘤的发生、发展过程中发挥着极为重要的作用。随着对Treg研究的不断深入,越来越多的证据表明Treg通过多种机制参与了肝癌特别是肝细胞肝癌的形成和发展,减少Treg数量能够增强患者的抗肿瘤免疫功能,是肝细胞肝癌预后的独立危险因子;反之,肝癌局部微环境的一些细胞因子能够影响Treg的表型,增强其抑制功能。     

白细胞介素2与调节性T细胞介导的免疫耐受

调节性T细胞(Tregs)可以诱导机体对自身抗原和过敏原产生免疫耐受,从而维持机体免疫稳态.白细胞介素(IL)-2是一种具有双向免疫调节作用的糖蛋白,其不仅可以增强免疫反应,更重要的是可以维持Tregs的稳定及其介导的免疫耐受.研究IL-2与Tregs功能活性及其介导的免疫耐受的关系对更好地了解免疫相关性疾病的发病机制和指导临床正确使用IL-2或IL-2拮抗剂具有重要意义.     

调节性T细胞在肿瘤及相关炎症中的研究进展

调节性T细胞(Tregs)是一种具有抑制免疫应答作用的T淋巴细胞亚群,在防止自身免疫病和维持自身耐受中起着重要作用,但其过度表达会导致免疫缺陷,慢性感染和癌症的发生.越来越多的研究表明,Tregs在肿瘤的发生发展和抑制肿瘤特异性免疫中起着重要作用.Tregs与人和小鼠模型中的实体瘤息息相关,乳腺癌、结直肠癌和卵巢癌中Tregs数量升高往往标志预后不良.因此调节外周血中Tregs水平成为了癌症治疗的新策略.     

The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression

Summary:  Tumor immunosurveillance relies on cognate immune effectors [lymphocytes and interferon-γ (IFN-γ)] and innate immunity [natural killer (NK) cells, natural killer group 2, member D (NKG2D) ligands, perforin/granzyme, and tumor necrosis factor-related apoptosis-inducing ligand]. In parallel, tumor cells promote the expansion of CD4⁺CD25⁺ regulatory T cells (Tregs) that counteract T-cell-based anti-tumor immunity. Moreover, accumulating evidence points to a critical role for Tregs in dampening NK cell immune responses. This review summarizes the findings showing that Tregs suppress NK cell effector functions in vitro and in vivo , i.e. homeostatic proliferation, cytotoxicity, and interleukin-12-mediated IFN-γ production. The molecular mechanism involve selective expression of membrane-bound transforming growth factor-β on Tregs, which downregulate NKG2D expression on NK cells in vitro and in vivo . The regulatory events dictating NK cell suppression by Tregs have been studied and are discussed. The pathological relevance of the Treg–NK cell interaction has been brought up in tumor models and in patients with cancer. Consequently, inhibition of Tregs through pharmacological interventions should be considered during NK-cell-based immunotherapy of cancer.     

Regulatory CD4+CD25+ T cells and macrophages: communication between two regulators of effector T cells

Regulatory T cells (Tregs) play an essential role in the induction and maintenance of peripheral tolerance as well as prevention of autoimmunity by limiting the strength of the immune response of effector T cells. Macrophages, a heterogeneous population of phagocytes and professional antigen presenting cells (APCs), can also exert suppressive effects on effector T cells to keep the peripheral balance of immunity. The bi-directional interactions of dendritic cells (DCs) and Tregs have been cell studied. However, much less is known about the reciprocal interaction between macrophages and Tregs. In this review, we will discuss recent observations regarding the interplay of these two regulators of immunity. Received 8 December 2006; returned for revision 17 January 2008; received from final revision 9 June 2008; accepted by G. Wallace 10 July 2008     

调节性T细胞参与肿瘤免疫的研究进展

调节性T细胞（Treg）对于介导免疫稳态、建立和维持自身耐受有重要作用.其对免疫反应具有抑制效应,保护机体免于发生自身免疫性疾病,并且可以抑制抗肿瘤免疫反应.近来研究发现,多种恶性肿瘤的患者外周血及肿瘤微环境中（Treg）增加,并且与预后具有相关性;去除Treg或者封闭其抑制功能可以增强抗肿瘤免疫反应.越来越多的证据表明Treg在肿瘤的进展过程和抑制肿瘤特异性免疫中扮演重要的角色.深入研究Treg的特点、功能和参与肿瘤免疫调节作用的机制将给肿瘤的预防和治疗提供新的思路和有效手段.     

Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination

Regulatory T cells (Tregs) are crucial players in balancing inflammation and antigen specific immune responses. In chronic infectious diseases, Tregs dampen inflammation to limit tissue damage, but they can also inhibit ensuing effector immunity, thereby impairing pathogen clearance. Chronic persistent infections by human pathogens such as parasites, viruses, and (myco)bacteria can all result in the induction of both CD4(+) and CD8(+) Tregs. However, among the many different subsets of Tregs that are induced, mostly CD4(+) Tregs have been studied. A remarkably increased frequency has been observed at the site of infection, supporting a role in pathogen containment. Indeed, antigen specificity has been demonstrated for several pathogen derived antigens. Here we review different classes of human Tregs in infectious diseases, including CD4 and CD8 Treg subsets. A better understanding of the induction and activity of Tregs is relevant for the design of better vaccines that optimally induce effector immunity without co-induction of excessive Treg activity.     

Co-stimulate or Co-inhibit Regulatory T Cells,Which Side to Go?

ABSTRACT

Co-stimulatory and co-inhibitory molecules direct the “second signal,” which largely determines the outcome of the “first signal” generated by the interaction of T cell receptor (TCR) with cognate MHC–peptide complex. The co-stimulatory and co-inhibitory signals are key mechanistic contributors to the regulation of adaptive immunity, especially the T cell–mediated immune response. Regulatory T cells (Tregs) are a special population of T cells, which unlike other T cells function as “attenuators” to suppress T cell immunity. Dysregulation of either the “second signal” or Tregs leads to an unbalanced immune system, which can result in a range of immune-related disorders, including autoimmune diseases, chronic infections, and tumors. In contrast, precise manipulation of these two systems offers tremendous clinical opportunities to treat these same diseases. Co-stimulatory and co-inhibitory molecules modulate immunity at molecular level, whereas Tregs delicately control the immune response at cellular level. Accumulating evidence has demonstrated that these two regulatory strategies converge and synergize with each other. This review discusses recent progress on the roles of co-stimulatory and co-inhibitory signals in the context of Tregs.     

Immune responses in neonates

Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in the understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in the neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents.