肝脏驻留NK细胞的发育分化及其个体发生

人和小鼠肝脏组织富含一群具有组织驻留特性的肝脏特有NK细胞,其与经典NK细胞在表型、功能、发育与分化等诸多方面具有显著差异。肝脏驻留NK细胞也被学界称为肝脏1型固有淋巴细胞,具有不成熟NK细胞的表型特征和很强的分泌细胞因子的能力,参与调节机体的免疫应答。肝脏驻留NK细胞与经典NK细胞受到不同转录因子的调控并呈现发育分化路径差异,在个体发生过程中的动态变化也不同。本文综述了肝脏驻留NK细胞的发现、发育分化、个体发生及微环境影响因素,为进一步对其深入研究提供新思路。     

NK细胞识别MHC Ⅰ类分子的机理

人及鼠Ｎ细胞上抑制性受体的结构功能已研究得较为清楚了。其识别ＭＨＣⅠ类分子的机理公认的“失去自己”的假说,具体作用模式为效应抑制模式和靶干扰模式,前者已越来越为实验所证实,本文对效应抑制模式的信号传导机制及ＮＫ细胞抑制性受体识别ＭＨＣ Ⅰ类分子位点的研究进行了综述。     

NK细胞受体识别的多样性

TCR和BCR介导T、B细胞的识别活化是现代免疫学研究的核心内容之一,比ICR和BCR更为复杂的是NK细胞的受体,迄今为止,已发现有数十种之多,分属抑制性受体和活化性受体两大类,各大类又包括数个家族,体现了NK细胞受体的多样性,介导了NK细胞的不同识别模式,分别传递不同的活化信号和抑制信号,各种信号在细胞表面如何整合,在细胞内部如何传递,最终赋予NK(细胞何种生物学功能,成为近期免疫学研究的热点问题。     

NK细胞的发育分化与功能极化

近十年来,NK细胞的研究有两大重要进展,一是发现NK细胞的受体多样性,二是发现NK细胞的功能多样性[1,2]。NK细胞受体主要由两个基因复合体集中编码,分别是人第19号染色体上的白细胞受体复合体(Leukocyte receptor complex,LRC)和第12号染色体上的NK细胞受体复合体(NK re-     

NK细胞识别和杀伤机制研究进展

NK细胞（Natural killer cell）是一类大颗粒淋巴细胞,存在于淋巴器官和外周组织中,行使多种重要功能：分泌细胞因子如IFN-γ,调节获得性免疫反应,防御感染以及溶解破坏肿瘤细胞等.NK细胞的主要特征是不需预先刺激就可直接溶解破坏肿瘤细胞和病毒感染细胞，通过分泌穿孔素、丝氨酸蛋白酶如颗粒酶A和B、硫酸软骨素蛋白聚糖等分子降解细胞膜、破坏靶细胞完整性而发挥溶细胞效应。本文旨在对NK细胞识别和杀伤机制作一综述，为深入研究NK细胞作用提供参考。     

小鼠肝脏NK细胞特有亚群:DX5-NK细胞

近来在小鼠中发现一群特殊的DX5-NK(DX5-NK1.1+CD3-)细胞,其具有不成熟NK细胞的表型(Ly49-CD11blowCD94hiNKG2+),且杀伤及分泌细胞因子能力明显低于经典的DX5+NK1.1+CD3-细胞.在不同脏器或不同年龄阶段,DX5-NK细胞的表型和功能均存在差别.成年小鼠体内的DX5-NK细胞主要分布于肝脏,占肝脏总NK细胞(CD3-NK1.1+)的50%左右.研究DX5-NK细胞将为了解NK细胞的组织特异性分布和NK细胞发育分化提供新线索.     

NK细胞识别MHC Ⅰ类分子的机理

人及鼠Ｎ细胞上抑制性受体的结构功能已研究得较为清楚了，其识别ＭＨＣⅠ类分子的机理公认的为“失去自己”假说，具体作用模式为效应抑制模式和靶干扰模式，前者已越来越为实验所证实。本文对效应抑制模式的信号传导机制及ＮＫ细胞抑制性受体识别ＭＨＣⅠ类分子位点的研究进行了综述。     

环境因素对滑膜细胞发育分化的影响

滑膜是由结缔组织转化而来的内衬膜状组织，与运动密切相关，本文介绍了近年来有关滑膜细胞的分化特征，发生发育及环境因素对滑膜细胞分化的影响的研究进展，并对目前存在的问题进行了分析。     

NK细胞的识别受体及作用

人ＮＫ细胞的识别受体基因组成Ｐ５８／ＮＫＡＴ基因家族，编码的蛋白是Ｉ型膜蛋白，属于Ｉｇ超家族成员。小鼠的ＮＫ细胞的识别受体基因组成Ｌｙ－４９基因家族。编码的蛋白质为Ⅱ型膜蛋白，属于Ｃ型凝集素超家族成员。ＮＫ细胞的识别受体能够识别自身细胞上的ＭＨＣＩ类分子和自身多肽形成的复合物，产生抑制性信号，使ＮＫ细胞的触发受体与细胞上的相应配体结合后杀伤性信号的产生被阻断，抑制了ＮＫ细胞的杀伤作用。否则，靶细胞     

环境因素对滑膜细胞发育分化的影响

滑膜是由结缔组织转化而来的内衬膜状组织，与运动密切相关。本文介绍了近年来有关滑膜细胞的分化特征、发生发育及环境因素对滑膜细胞分化的影响的研究进展，并对目前存在的问题进行了分析     

Lymphokine-activated killer cells, natural killer cells and cytokines

In the past year, natural killer cells have been the subject of much active investigation. The analysis of the effect of cytokines on the generation, proliferation and function of natural killer cells, and the definition of the lymphokines that they produce, have been particularly important areas of research in view of their possible application in adaptive immunotherapy, combined with biological response modifiers.     

Regulation of immune responses by natural killer T cells

Natural killer T (NKT) cells, which comprise a minor population of T cells in primary and secondary lymphoid organs, possess phenotypic characteristics of both NK and T cells. NKT cells respond to various external stimuli by an early burst of cytokines, including IL-4 and IFN-gamma. Thus, a key immunoregulatory role has been attributed to them. Autoimmune diseases, especially type I diabetes (TID), may be caused by dysregulation of the immune system, which leads to hyporesponsiveness of regulatory T helper 2 (Th2) cells and promotion of autoimmune Th1 cells. Furthermore, several lines of evidence exist to support the notion that an NKT cell deficiency in individuals at risk of TID may be causal to TID. As a result, targeting NKT cells using immunotherapeutic agents may prove beneficial in the prevention or recurrence of TID. Indeed, our data demonstrate that stimulation of NKT cells with a specific ligand prevents the onset and recurrence of TID in nonobese diabetic (NOD) mice.     

Development and tolerance of natural killer cells.

A natural killer (NK)/T-cell-restricted progenitor cell in the fetal blood, with a phenotype of NK1.1(+) CD117 (c-kit)+, can give rise to NK cells. IL-15 is probably required for NK cell differentiation and, in addition, stimulates expression of at least one of the MHC-specific inhibitory receptor families expressed by NK cells. Evidence supports the role of multiple mechanisms in rendering NK cells self tolerant - including selection for expression of self-specific inhibitory receptors, anergy and modulation of the cell surface levels of MHC-specific inhibitory receptors.     

Germline-encoded recognition of diverse glycolipids by natural killer T cells

Natural killer T cells expressing 'invariant' T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J) region V(alpha)14-J(alpha)18 (V(alpha)14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRalpha chain and a restricted set of TCRbeta chains recognize structurally diverse antigens is not clear. Here we show that a V(alpha)14i TCR recognized many alpha-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3alpha, 1alpha and 2beta. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the V(alpha)14i TCR functions as a pattern-recognition receptor, conferring on natural killer T cells the ability to sense and respond in an innate way to pathogens displaying antigenic alpha-linked glycolipids.