NKT细胞在妊娠免疫调节中的作用

NKT细胞是具有限制性识别由CD1d提呈脂类和糖脂类抗原的T细胞,其既表达T细胞谱系标志αβTCR和CD3,又表达NK细胞谱系标志CD56。NKT细胞具有NK细胞相同的杀伤靶细胞作用,并兼有分泌产生Th1与Th2相关细胞因子及CD8＋细胞毒性T细胞（cytotoxic T lymphocyte,CTL）的细胞毒作用。因而,NKT细胞在免疫调节系统中占有重要位置。最近研究发现NKT细胞存在于母胎界面,且活化的NKT细胞在妊娠的免疫调节中具有重要作用。     

一种新型免疫细胞—NKT细胞

NKT细胞（natural killer T cells)是一类表达NK细胞表面分不志的α/βT淋巴细胞，具有迅速分泌大量细胞因子的能力，能够对效应细胞提供早期的辅助以及在一些免疫反应中调控TH1和TH2辅助细胞的分化，NKT细胞识别由CD1d分子提呈的抗原，其作用机理既不同于NK细胞也不同于T，B淋巴细胞，在一些自身免疫性疾病，肿瘤监视及抗肿瘤方面有着非常重要的作用。     

iNKT细胞在系统性红斑狼疮发病机制中的研究进展

iNKT细胞是T细胞的一个亚群,表达T细胞表面受体（TCR）和NK细胞表面标志物NK1．1（人类为CD161）,能够被非经典MHC-I类分子CD1d提呈的糖脂抗原所激活,不仅具有T细胞的免疫调节作用,也具有NK细胞的自然杀伤作用。近年来的研究发现iNKT细胞在多种自身免疫性疾病,包括系统性红斑狼疮（Systemic Lupus Erythematosus,SLE）的发生中扮演重要角色,但具体机制还不明确。     

NKT细胞在母胎界面免疫调节中的作用

NKT细胞(natural killer T cell)是一类新型的免疫调节细胞,该类细胞同时表达T细胞表面受体(TCR)和NK细胞的抗原NK1.1。NKT细胞上的TCR通过限制性识别由CD1d分子提呈的脂类抗原,进一步被激活后可分泌多种细胞因子,从而调节机体的免疫反应。近年来逐渐认识到NKT细胞可能参与了母胎界面的免疫调节。     

NKT细胞与调节性T细胞在免疫调节中相互作用的研究进展

NKT细胞和调节性T细胞是2种有效的免疫调节细胞,能独立调节先天性和获得性免疫反应。近年来,大量研究表明NKT细胞和调节性T细胞之间存在复杂的双向调节:活化的NKT细胞通过影响抗原提呈细胞的功能、依赖IL-2信号机制等作用促进调节性T细胞的功能,调节性T细胞通过细胞接触、分泌抑制性细胞因子等方式抑制NKT细胞的增殖、细胞因子释放和细胞毒活性等,两者相互协同调控机体的免疫应答。本文就NKT细胞和调节性T细胞在免疫调节中的相互作用的研究进展做一综述。     

NKT细胞与肝纤维化的研究进展北大核心CSCD

自然杀伤T细胞(NKT)是一类具有NK细胞受体和T细胞受体且显示NK细胞和T细胞两方面性质的T细胞亚群,NKT将先天性免疫应答和获得性免疫应答连接起来,限制性识别CD1d-糖脂类抗原,活化后迅速分泌大量细胞因子从而调节机体的免疫应答。人体的肝脏内富含NKT细胞,因此,NKT细胞在肝脏中的作用引起了人们的广泛兴趣。本文总结了近年来NKT细胞在肝纤维化发生发展中的免疫学研究进展。     

固有免疫细胞在急性肾损伤中的研究进展

固有免疫细胞在急性肾损伤(AKI)中的免疫应答反应起至关重要的作用,常见的先天免疫细胞包括中性粒细胞、巨噬细胞、树突状细胞(DC)、自然杀伤(NK)细胞及自然杀伤T(NKT)细胞。这些免疫细胞通过表达和分泌细胞因子、趋化因子以及抗原提呈在AKI中激活免疫应答,从而发生一系列免疫炎症反应,成为AKI后的致病及修复的关键点。了解与先天免疫细胞相关的趋化因子、分子途径可作为日后治疗靶点改善AKI。     

NKT细胞与HIV-1相关性的研究

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。由于其表型功能与T细胞、B细胞和NK细胞等免疫细胞有所不同,NKT细胞可以识别由CD1d提呈的特异糖脂分子并具有迅速分泌大量细胞因子, 参与机体先天性免疫及获得性免疫反应的能力, 在调节机体Th1 /Th2免疫网络平衡中具有重要的作用。最新研究表明NKT细胞是人类免疫缺陷病毒 1 (HIV 1)靶细胞之一, 在AIDS患者体内选择性减少。本文拟从NKT细胞分类、分布、表型特征及与HIV 1作用机制和治疗前景进行综述。1　NKT细胞分类及分布1987…     

树突状细胞在抗HIV-1感染免疫预防与治疗中的应用

树突状细胞（DC）不仅是已知惟一能够激活初始T淋巴细胞的抗原提呈细胞，而且也是已知最强的抗原提呈细胞（APC），其对抗原的提呈能力远大于巨噬细胞。经抗原刺激的DC回输到体内后，能够迁移到淋巴结，释放多种细胞因子，同时激活T淋巴细胞的分化和分裂，产生抗原特异性的细胞毒性T淋巴细胞（CTL），这些细胞因子和特异性CTL能够有效地促进或直接杀伤表达该抗原的细胞。基于这个原理，利用HIV-1抗原刺激DC所诱导的免疫对HIV-1感染进行免疫预防和治疗的研究已取得初步进展；将高效抗逆转录病毒疗法（highly active antiretroviral therapy，HARRT）和DC免疫治疗相结合的方案也已成为治疗AIDS的较好方法之一。本文中将对近年来DC在抗HIV-1感染免疫预防与免疫治疗中的应用研究进展作一综述。     

NKT细胞在乙型病毒性肝炎治疗中作用的研究进展

自然杀伤性T细胞（NKT细胞）是一种同时具有自然杀伤细胞（NK细胞）和T细胞部分表型及功能的细胞亚群。它们能将固有免疫应答和适应性免疫应答连接起来，识别CDld-糖脂抗原，分泌细胞因子，参与调节机体的免疫应答。由于机体一些器官中（如肝脏）富含NKT细胞，因此NKT细胞在肝脏中的作用引起了人们的广泛兴趣。NKT细胞参与机体对乙型肝炎病毒的免疫应答，它们一方面抑制病毒复制，另一方面引起肝脏的免疫损伤，因而研究NKT细胞及其在乙型病毒性肝炎治疗中的作用可以对乙型病毒性肝炎的治疗提供新的思路。     

Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses

Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T-cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4⁺ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha-galactosylceramide (αGalCer)-activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell-specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses.     

Natural killer T cell anergy,co-stimulatory molecules and immunotherapeutic interventions

Natural killer T (NKT) cells are a unique subset of glycolipid-reactive T lymphocytes that share properties with natural killer (NK) cells. These lymphocytes can produce array of cytokines and chemokines that modulate the immune response, and play a pivotal role in cancer, autoimmunity, infection and inflammation. Owing to these properties, NKT cells have gained attentions for its potential use in antitumor immunotherapies. To date several NKT cell-based clinical trials have been performed in patients with cancer using its potent ligand α-galactosylceramide (α-GalCer). However, inconsistent therapeutic benefit, and inevitable health risks associated with drug dose and NKT cell activation have been observed. α-GalCer-activated NKT cells become anergic and produce both Th1 and Th2 cytokines that may function antagonistically, limiting the desired effector functions. Besides, various co-stimulatory and signaling molecules such as programmed death-1 (PD-1; CD279), casitas B-cell lymphoma-b (Cbl-b) and CARMA1 have been shown to be implicated in the induction of NKT cell anergy. In this review, we discuss the role of such key regulators and their functional mechanisms that may facilitate the development of improved approaches to overcome NKT cell anergy. In addition, we describe the evidences indicating that tailored-ligands can optimally activate NKT cells to obtain desired immune responses.     

Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development

Commitment to the T and natural killer T (NKT) cell lineages is determined during alphabeta T cell receptor (TCR)-mediated interactions of common precursors with ligand-expressing cells in the thymus. Whereas mainstream thymocyte precursors recognize major histocompatibility complex (MHC) ligands expressed by stromal cells, NKT cell precursors interact with CD1d ligands expressed by cortical thymocytes. Here, we demonstrated that such homotypic T-T interactions generated "second signals" mediated by the cooperative engagement of the homophilic receptors Slamf1 (SLAM) and Slamf6 (Ly108) and the downstream recruitment of the adaptor SLAM-associated protein (SAP) and the Src kinase Fyn, which are essential for the lineage expansion and differentiation of the NKT cell lineage. These receptor interactions were required during TCR engagement and therefore only occurred when selecting ligands were presented by thymocytes rather than epithelial cells, which do not express Slamf6 or Slamf1. Thus, the topography of NKT cell ligand recognition determines the availability of a cosignaling pathway that is essential for NKT cell lineage development.     

Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases

Both osteopontin (OPN) and natural killer T (NKT) cells play a role in the development of immunological disorders. We examined a functional link between OPN and NKT cells. Concanavalin A (Con A)-induced hepatitis is a well-characterized murine model of T cell-mediated liver diseases. Here, we show that NKT cells secrete OPN, which augments NKT cell activation and triggers neutrophil infiltration and activation. Thus, OPN- and NKT cell-deficient mice were refractory to Con A-induced hepatitis. In addition, a neutralizing antibody specific for a cryptic epitope of OPN, exposed by thrombin cleavage, ameliorated hepatitis. These findings identify NKT cell-derived OPN as a novel target for the treatment of inflammatory liver diseases.     

Regulation of immune responses by CD1d-restricted natural killer T cells

Natural killer T (NKT) cells are a unique subset of T lymphocytes that share receptor structures and properties with conventional T lymphocytes and natural killer (NK) cells. NKT cells are specific for glycolipid antigens such as the marine sponge-derived agent α-galactosylceramide (α-GalCer) presented by the major histocompatibility complex (MHC) class I-like molcule CD1d. My laboratory has evaluated the function of NKT cells by generating and analyzing CD1d-deficient mice. These studies showed that CD1d expression is required for NKT cell development, but not absolutely necessary for the generation of polarized T helper (Th) cell responses. Further, we have studied the in vivo response of NKT cells toα-GalCer stimulation and the capacity of α-GalCer to modulate innate and adaptive immune responses. Our results revealed that, quickly following administration of α-GalCer, NKT cells expand and produce cytokines, trans-activate a variety of innate and adaptive immune cells, and promote Th2 responses that are capable of suppressing Th1-dominant autoimmunity. Our findings indicate that NKT cells play a regulatory role in the immune response and that specific activation of these cells may be exploited for therapeutic purposes.     

Activated CD1d-restricted natural killer T cells secrete IL-2: innate help for CD4+CD25+ regulatory T cells?

CD4(+)CD25(+) and CD1d-restricted natural killer T (NKT) cells are thymus-derived self-reactive regulatory T cells that play a key role in the control of pathological immune responses. Little is known about functional cooperation between innate regulatory NKT cells and adaptive CD4(+)CD25(+) regulatory cells. Here we show that human CD4(+)Valpha24(+)Vbeta11(+) (CD4(+) NKT) cells isolated from peripheral blood by flow cytometric cell sorting secrete substantial amounts of IL-2 after stimulation with dendritic cells (DC) and alpha-Galactosylceramide. When cocultured with CD4(+)CD25(+) cells, CD4(+) NKT cells promoted moderate proliferation of CD4(+)CD25(+) cells. The proliferation of CD4(+)CD25(+) T cells was due to soluble IL-2 produced by activated CD4(+) NKT cells. The expanded CD4(+)CD25(+) cells remained anergic and retained their potent suppressive properties. These findings indicate that unlike conventional CD4(+) and CD8(+) T cells, which are susceptible to CD4(+)CD25(+) regulatory cell suppression, NKT cells promote CD4(+)CD25(+) regulatory cell proliferation. These data raise the possibility that NKT cells can function as helper cells to CD4(+)CD25(+) regulatory T cells, thereby providing a link between the two naturally occurring populations of regulatory T cells.     

Comparative gene expression analysis of NKT cell subpopulations

Natural killer T (NKT) cells are a lymphocyte lineage, which has diverse immune regulatory activities in many disease settings. Most previous studies have investigated the functions of this family of cells as a single entity, but more recent evidence highlights the distinct functional and phenotypic properties of NKT cell subpopulations. It is likely that the diverse functions of NKT cells are regulated and coordinated by these different NKT subsets. Little is known about how NKT subsets differ in their interactions with the host. We have undertaken the first microarray analysis comparing the gene expression profiles of activated human NKT cell subpopulations, including CD8(+) NKT cells, which have often been overlooked. We describe the significant gene expression differences among NKT cell subpopulations and some of the molecules likely to confer their distinct functional roles. Several genes not associated previously with NKT cells were shown to be expressed differentially in specific NKT cell subpopulations. Our findings provide new insights into the NKT cell family, which may direct further research toward better manipulation of NKT cells for therapeutic applications.     

Regulation of autoimmune disease by natural killer T cells

Natural killer T (NKT) cells express phenotypic characteristics shared by conventional natural killer cells and T cells, and reside in several primary and secondary lymphoid as well as nonlymphoid organs. Although these cells possess important effector functions in immunity against cancer and microbial pathogens, their immunoregulatory function has received much recent attention. There is convincing evidence to suggest a regulatory role for these cells in the control of susceptibility to autoimmune disease. NKT cells are reduced in number and function in autoimmune disease prone mice and humans. Studies conducted in mice have shown that transfer of NKT cells to disease-susceptible recipients prevents the development of autoimmune disease. The recent discovery that alpha-galactosylceramide, a glycolipid, can specifically target NKT cells expressing the invariant T cell receptor (TCR) to proliferate and produce an array of regulatory cytokines and chemokines has generated considerable interest to utilize these cells as targets of new therapeutic interventions for the immunoregulation of autoimmune disease