NKT 细胞在动脉粥样硬化中的作用*

然杀伤T细胞(natural killer T cell,NKT细胞)是一种特殊的淋巴细胞亚群,具有部分T细胞和NK细胞的特征。与这些细胞不同的是,NKT细胞不仅能够识别醣脂类抗原,还在激活后产生促炎症因子和抗炎症因子。由于这些特性,NKT细胞在炎症和免疫方面的研究越来越热。动脉粥样硬化是一种受免疫调节的炎性疾病,因此对NKT细胞在该疾病中作用的研究也逐渐开展起来。     

NK细胞和NKT细胞发育的转录调控

自然杀伤（natural killer,NK）细胞和自然杀伤T（natural killer T,NKT）细胞是参与机体抗病毒免疫和肿瘤免疫的两群淋巴细胞亚群,是介导先天性免疫（innate immunity）应答和调节适应性免疫（adaptive immunity）应答的重要效应细胞。近年来,随着对NK细胞和NKT细胞及其转录调控因子研究的不断深入,NK细胞和NKT细胞的发育机制逐步被阐明,这将为提高NK细胞和NKT细胞的抗病毒和肿瘤免疫疗效提供新的策略。     

自然杀伤T细胞的研究进展

自然杀伤T细胞(NKT)是一类具有NK受体和T细胞受体且显示NK细胞和T细胞两方面性质的淋巴细胞.因其表型和功能与T细胞,B细胞和NK细胞等免疫细胞有所不同,近年来颇受关注.NKT细胞具有高度保守的TCR表型(TCRVα24/β11-人),同时共表达NK细胞特有标志CD161.NKT细胞识别由CD1d分子提呈的特异糖脂分子,并能够分泌大量细胞因子,参与机体的先天性免疫和获得性免疫反应.研究发现,NKT细胞在抗感染,抗肿瘤,以及抑制自身免疫性疾病(如:肥胖型糖尿病,再生障碍性贫血等)的发生中发挥着重要作用.本文将对有关NKT细胞特征和功能的研究现状,以及存在的问题作一综述.     

MiR-150缺失增强小鼠NKT细胞IFN-γ产生并抑制黑色素瘤细胞的肺转移

CD1d限制性NKT细胞(自然杀伤T细胞)是一群具有免疫调节功能的T细胞亚群,在调控多种免疫应答中发挥重要作用．MicroRNAs介导的RNA干扰已被证明是调控NKT细胞发育和功能的关键分子机制,然而特异microRNA在NKT细胞发育和功能中的作用目前仍不清楚．在本研究中,我们采用miR-150基因敲除小鼠以及流式细胞术、ELISA等方法,观察miR-150对小鼠NKT细胞发育和功能的影响．结果表明：miR-150基因缺失致小鼠胸腺NKT细胞数量减少,但不影响外周NKT细胞的数量;活化后miR-150敲除小鼠NKT细胞与野生型小鼠NKT细胞相比,IFN-γ产生增加．进一步采用小鼠黑色素瘤模型观察miR-150对肿瘤细胞转移的影响,发现miR-150敲除显著增强半乳糖神经鞘氨醇(α-Galcer)对小鼠黑色素瘤细胞肺转移的抑制效果．上述结果为特异microRNA调控NKT细胞发育和功能的研究提供了新的线索．     

恒定自然杀伤T细胞与肿瘤免疫治疗北大核心CSCD

恒定自然杀伤T细胞(i NKT)是T淋巴细胞的一个独特亚群,兼具自然杀伤(NK)细胞和T细胞特征,同时表达T细胞受体(TCR)和NK细胞表面标志。i NKT细胞被激活后,通过分泌细胞因子,活化其它免疫细胞参与先天性免疫和获得性免疫,在抗肿瘤免疫过程中发挥调节作用。在多种癌症患者体内,发现外周血中i NKT细胞的数量降低、功能减弱,进而导致临床治疗效果不佳。近年来,基础研究和早期临床试验结果表明,注射抗原递呈细胞或/和体外培养并活化的i NKT细胞,抗肿瘤免疫治疗效果显著。本文就i NKT细胞的分类及生物学特性,在肿瘤免疫治疗中的作用与其机制,以及其临床应用等进行综述。     

自然杀伤T细胞抗感染作用的研究进展

自然杀伤T细胞(NKT细胞)是一类与自然杀伤细胞具有共同表面标记的T细胞,可识别由CD1d呈递的糖脂类抗原。活化后的NKT细胞通过分泌多种细胞因子和趋化因子,增强树突细胞(DC)、T细胞、B细胞等多种免疫细胞的功能,在非特异与特异性免疫之间起桥梁作用。近年来研究发现,NKT细胞不仅在抗细菌感染中发挥重要作用,在抗病毒及抗寄生虫感染中也发挥一定作用。     

自然杀伤T细胞抗胞内菌感染的研究进展

自然杀伤T细胞(NKT细胞)是免疫细胞中一类具有特定标记的T细胞亚群,能特异性识别南抗原呈递细胞表面CD1d分子所呈递的糖脂类抗原.活化后的NKT细胞能分泌多种细胞因子,参与机体的天然免疫和获得性免疫反应,还能直接杀伤靶细胞,具有效应细胞的功能.研究发现,NKT细胞在抗胞内菌感染中发挥着重要作用.     

NKT细胞亚群

经典的NKT细胞是一类表面既具有T细胞又具有NK细胞标志的T细胞亚群。与普通T细胞相比,1.NKT细胞不受经典MHC I类分子限制,而受非经典MHC I类分子、CD1d分子限制,不识别蛋白质抗原,而是识别脂类抗原;2.NKT细胞的TCR     

CD1d/NKT在抗HBV和HCV中的作用

CD1d是人类白细胞表面的抗原分子,它可以将脂质抗原递呈给天然杀伤T细胞（NKT）,使其激活.而NKT是近年来发现的一类特殊的T细胞,它既可以表达T细胞表面标志,又可以表达天然杀伤细胞（NK）表面标志,能识别由CD1d递呈的抗原,广泛参与自身免疫调节.近年来,许多研究发现,CD1d/NKT可以有效抑制肝炎病毒的复制.     

NKT细胞抑制或增强抗肿瘤免疫反应的机制

自然杀伤性T细胞是表达NK细胞表面标志的一类特殊T细胞,对免疫系统具有重要的调节功能.在抗肿瘤的免疫反应中表现抑制或增强的不同作用,该文介绍NKT细胞通过分泌IL-12激活效应细胞对抗肿瘤作用的分子机制;并阐释在动物模型中NKT细胞分泌IL-13调控STAT-6信号途径,下调免疫监视并抑制抗肿瘤的作用;以及目前提出的NKT细胞在抗肿瘤免疫中的协调作用机制.     

NKT细胞在抗肿瘤免疫中的作用及其机制

NKT细胞是免疫细胞中一类具有NK细胞特定标志的T细胞亚群,经活化,既可直接作为抗肿瘤效应细胞发挥杀伤作用,又能通过激活其他免疫效应细胞,如NK细胞,间接实现抗肿瘤作用。NKT细胞在抗肿瘤免疫、获得性免疫应答及免疫调节中起着重要作用。     

Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes

Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.     

Role of NKT cells in the digestive system. III. Role of NKT cells in intestinal immunity

Natural killer T (NKT) cells are a small subset of unconventional T cells that recognize lipid antigens presented by the nonclassical major histocompatibility complex (MHC) class I molecule CD1d. NKT cells are involved in the host response to a variety of microbial pathogens and likely commensals. In the intestine, invariant and noninvariant NKT cells can be found among intraepithelial lymphocytes and in the lamina propria. Activation of intestinal NKT cells by CD1d-expressing intestinal epithelial cells and professional antigen-presenting cells may contribute to induction of oral tolerance and protection from mucosal infections. On the other hand, sustained and uncontrolled activation of NKT cells may play a pivotal role in the pathogenesis of inflammatory bowel disease. Here we review the current literature on intestinal NKT cells and their function in the intestine in health and disease.     

产白介素-17T细胞在肺部细菌感染中的研究进展

目前产白介素-17(IL-17)T细胞主要包括了产IL-17 CD4+T细胞即Th17细胞、产IL-17γδT细胞和产IL-17 CD8+T细胞等。随着对Th17这一系细胞功能研究的不断深入,发现它们能通过产生IL-17和IL-22等细胞因子参与炎症反应。该文将对产IL-17 T细胞在肺部细菌感染中所起作用的最近研究进展进行综述。     

Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells

Natural killer T (NKT) cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo)) and mature (NK1.1(hi)) cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder)), that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.     

Natural killer T cells: rapid responders controlling immunity and disease

Natural killer T (NKT) cells are a subset of T cells that share properties of natural killer cells and conventional T cells. They are involved in immediate immune responses, tumor rejection, immune surveillance and control of autoimmune diseases. Most NKT cells express both an invariant T cell antigen receptor and the NK cell receptor NK1.1, and are referred to as invariant NKT cells. This invariant T cell receptor is restricted to interactions with glycolipids presented by the non-classical MHC, CD1d. These NKT cells rapidly produce high levels of interleukin (IL)-2, IFN-gamma, TNF-alpha, and IL-4 upon stimulation through their TCR. Most also have cytotoxic activity similar to NK cells. NKT cells are involved in a number of pathological conditions, and have been shown to regulate viral infections in vivo, and control tumor growth. They may also play both protective and harmful roles in the progression of certain autoimmune diseases, such as diabetes, lupus, atherosclerosis, and allergen-induced asthma.     

Presumed guilty: natural killer T cell defects and human disease

Natural killer T (NKT) cells are important regulatory lymphocytes that have been shown in mouse studies, to have a crucial role in promoting immunity to tumours, bacteria and viruses, and in suppressing cell-mediated autoimmunity. Many clinical studies have indicated that NKT cell deficiencies and functional defects might also contribute to similar human diseases, although there is no real consensus about the nature of the NKT cell defects or whether NKT cells could be important for the diagnosis and/or treatment of these conditions. In this Review, we describe the approaches that have been used to analyse the NKT cell populations of various patient groups, suggest new strategies to determine how (or indeed, if) NKT cell defects contribute to human disease, and discuss the prospects for using NKT cells for therapeutic benefit.     

The regulatory role of natural killer T cells in the airways

Asthma, an inflammatory disorder of the airways, has been considered a disease mediated by allergen-specific Th2 cells and eosinophils, and controlled by allergen-specific regulatory T cells. This paradigm can explain many but features of asthma, but Th2 targeted therapies in patients with asthma have not been as successful as might be predicted by this paradigm. These observations have suggested that other cell types, such as Natural Killer T cells, may play an important role in asthma. In this review, we discuss the data that support the notion that NKT cells critically regulate the development of asthma.     

Cytokine-induced inflammatory liver injuries

IL-18 is a pleiotropic cytokine and is produced by various types of cells including activated macrophages, particularly Kupffer cells. IL-18 has potential to activate inflammatory responses through induction of IFN-gamma production in collaboration with IL-12. Somewhat paradoxically, IL-18 also has the capacity to induce allergic responses via induction of IL-4 production by T helper cells and to activate mast cells and basophils to release atopic effector molecules such as histamine. Indeed, IL-18 is involved in inflammatory tissue injuries, such as Crohn's disease and atherosclerosis, and also in hyper IgE and atopic dermatitis. IL-18 is particularly important for induction of experimental liver diseases. Endotoxin-induced liver injury or Fas ligand-induced hepatitis is caused by endogenous IL-18 in mice. Moreover, patients with liver diseases such as fulminant hepatitis, liver cirrhosis due to hepatitis virus infection and primary biliary cirrhosis show elevation of serum levels of IL-18, that correlates with the corresponding disease severity. Therefore, endogenous IL-18 plays a major role in induction of some types of liver injuries in mice and human. NKT cells that express both T cell receptor and NK cell marker are abundant in the liver of mice and human. Recent studies have revealed that NKT cells participate in some types of liver injuries, such as concanavalin A-induced T cell-mediated hepatitis and malaria hepatitis. In this review article, we focus on IL-18-involving liver damages and NKT-cell-mediated liver injuries.