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目的探讨异基因骨髓移植小鼠体内调节性T细胞（Treg）、NK细胞以及与其功能相关的细胞因子白介素-10（IL-10）、转化生长因子（TGF-β）、穿孔素与急性移植物抗宿主病（aGVHD）的关系。方法建立H-2完全不合的C57BL/6→BALB/c纯种小鼠间异基因骨髓移植后发生aGVHD模型。流式细胞仪检测移植后存活的aGVHD小鼠脾脏CD4＋CD25＋Treg细胞和NK-1.1＋NK细胞的比例;ELISA方法检测环孢素A干预aGVHD小鼠血清IL-10、TGF-β和穿孔素的水平,以正常的C57BL/6小鼠为对照。结果与正常小鼠相比,移植后发生aGVHD小鼠体内Treg细胞比例下降（3.6%vs.1.55%）,NK细胞比例上升（3.3%vs.11.5%）;环孢素A治疗aGVHD组小鼠,与未干预组相比,血清IL-10水平明显上升[（125.79±0.27）pg/mL vs.（103.09±3.27）pg/mL,P〈0.01],TGF-β水平上升但无统计学差异[（252.05±7.84）pg/mL vs.（241.61±15.41）pg/mL,P〉0.05],穿孔素水平明显上升[（186.97±4.68）pg/mLvs.（144.35±14.42）pg/mL,P〈0.01]。结论 （1）小鼠移植后发生aGVHD与Treg细胞比例下降有关,Treg功能相关的细胞因子IL-10、TGF-β参与环孢素A介导的免疫抑制治疗;（2）NK细胞参与异基因骨髓移植后aGVHD的发生过程,穿孔素的水平上升与抑制aGVHD有关。

自然杀伤（natural killer,NK）细胞是先天性免疫效应细胞,约占人外周血淋巴细胞总数的10%-15%,主要参与免疫监视,以消除转化细胞和病毒感染细胞。NK细胞最初被界定是由于它们具有自发消除少数主要组织相容性复合物I类（major histocompatibility class I,MHC-I）自身分子表达缺乏细胞的能力,即常说的＂丢失自我＂识别能力。NK细胞表面表达的MHC-I特异性抑制性受体,可使NK细胞对表达MHC-I的正常细胞耐受,此为丢失自我识别能力的分子基础。由于缺乏抑制性受体的配体,表面MHC-I表达下调的肿瘤细胞和病毒感染细胞易受NK细胞攻击。杀伤细胞免疫球蛋白样受体（KIR;CD158）组成MHC-I结合受体家族,对调节人NK细胞和部分T细胞的活化阈值起重要作用。KIR多样性使NK细胞具有多种功能,在此我们将综述多个水平上的KIR多样性,并诠释KIR多样性是如何影响各种疾病（包括癌症）的易感性的。我们将进一步阐述通过针对KIR进行癌症治疗的策略：利用KIR/MHC-I配体的错配以强化造血干细胞移植的效果,以及通过阻滞KIR以增强对肿瘤细胞的杀伤力。

目的检测炎症性肠病（IBD）即溃疡性结肠炎（UC）及克罗恩病（CD）患者外周血淋巴细胞表面白介素-23（IL-23）受体的表达情况，并讨论其在疾病发生中的意义。方法收集30例UC患者、16例CD患者和30例正常对照者的外周血，分离外周血单个核细胞（PBMC），采用三色流式细胞术检测IBD患者外周血CD4^＋T、CD8^＋T和CD56^＋NK细胞表面IL-23受体（IL-23R）的表达，并与正常外周血比较。结果UC及CD患者外周血中CD4^＋T、CD8^＋T、CD56^＋NK细胞表面IL-23R的表达明显高于对照组（P〈0．05）。结论IBD患者外周血淋巴细胞表面IL-23R的表达增高，提示IL-23R在IBD的发病过程中起重要作用。

R735.705

R734.2

背景与目的分析与结外鼻型NK/T细胞淋巴瘤（extra-nodal NK/T-celllym phoma,nasaltype,ENKTCL-N）预后密切相关的临床病理因素;通过基因芯片检测和监督聚类分析，筛选与该肿瘤侵袭机制密切相关的基因；验证基因芯片筛选所获得的基因在ENKTCL-N的表达情况，以及与预后的关系。

目的研究表达US3基因重组腺病毒载体对其转染肝细胞介导的免疫逃逸活性。方法首先构建表达US3基因腺病毒载体,扩增纯化后转染HL-7702肝细胞,利用细胞毒性T细胞（CTL）杀伤实验和自然杀伤细胞（NK）杀伤实验,检测表达US3基因重组腺病毒载体的免疫活性。结果表达US3基因的重组腺病毒r-US3成功构建,r-US3能够明显降低CTL和NK细胞对转染肝细胞的杀伤活性。结论表达US3基因腺病毒载体在一定程度上能够介导转染肝细胞的免疫逃逸,降低机体免疫系统对转染肝细胞的排斥反应。

Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

Natural killer （NK） cell education, a process for achieving functional maturation and self-tolerance, has been previously defined by the interaction between self-major histocompatibility complex class I （MHC-I） molecules and their specific inhibitory receptors. Over the past several years, growing evidence has highlighted the important roles of nonclassical MHC-I and non-MHC-I molecules in NK cell education. Herein, we review the current knowledge of NK cell education, with a particular focus on nonclassical MHC-I- and non-MHC-I-dependent education, and compare them with the classical MHC-I-dependent education theory. In addition, we update and extend this theory by presenting the ＇Confining Model＇, discussing cis and trans characteristics, reassessing quantity and quality control, and elucidating the redundancy of NK cell education in tumor and virus infection.

Decidual natural killer （dNK） cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 （Tim-3） are expressed on over 60% of dNK cells. Tim-3^＋ dNK cells display higher interleukin （IL）-4 and lower tumor necrosis factor （TNF）-α and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 （Gal-9） and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide （LPS）-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper （Th）2-type cytokines were decreased and Thl-type cytokines were increased in Tim-3^＋ but not Tim-3- dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.