树突状细胞与趋化因子的研究进展

趋化因子可分为４个亚家族，其中Ｃ－Ｃ家族的成员最多，不同家族的趋化因子具有不同的结构及功能特点，趋化因子受体属于Ｇ蛋白偶联受体超家族，是一含有７个疏水性穿膜区段的单链受体，大多数趋化因子受体能结合同一个亚家族中多个成员，ＤＣ表达高水平ＣＣＲ１，ＣＣＲ２和ＣＣＲ５，以及ＣＸＣＲ１，ＣＸＣＲ２和ＣＸＣＲ４，这些受体通过结合相应的趋化因子诱导ＤＣ的趋化反应，在ＤＣ的迁移过程中起重要作用，ＤＣ表达的趋化因     

趋化因子受体HIV-1

β－趋化因子受体５（ＣＣＲ５）是近年来新克隆的趋化因子受体超基因家族的一个重要成员之一,由于它的被发现才使人们认识到ＨＩＶ－１ 的感染除了Ｔ 细胞上的ＣＤ４＋ 外还有另一条通过巨噬细胞表面辅助受体ＣＣＲ５ 介导的传播途径。本文就近年来有关趋化因子受体基因家族的组成成员、结构与功能、不同人种的基因型、ＨＩＶ－１ 与细胞表面辅助受体ＣＣＲ５ 的结合,进入机理及阻断ＨＩＶ－１ 感染的可能途径作一详要的综述     

趋化因子受体HIV—1

β－趋化因子受体５是近年来新克隆的趋化因子受体超基因家族的一个重要成员之一,由于它的被发现才使人们认识到ＨＩＶ－１的感染除了Ｔ细胞上的ＣＤ４＾＋外还有另一条通过巨噬细胞表面辅助受体ＣＣＲ５介导的传播途径。     

人类免疫缺陷病毒包膜糖蛋白V3区对细胞结合能力的研究

目的：研究人类免疫缺陷病毒（ＨＩＶ）不同亲嗜株包膜糖蛋白Ｖ３区结合于靶细胞的能力。方法：合成来源于不同嗜性ＨＩＶ－１Ｖ３区的生物素标记和非标记的多肽。采用流式细胞计数分析生物素化的 Ｖ３多肽对细胞的结合能力以及细胞表面的结合配体。结果：ＨＩＶ－１Ｘ４　亲嗜株ＩＩＩＢＶ３区能结合于多种细胞的表面，包括辅助受体ＣＸＣＲ４；竞争实验结果显示蛋白酶抑制剂能抑制该结合。Ｒ５亲嗜株 ＡＤＡ Ｖ３区只极微弱地结合于外周血单核细胞和表达ＣＣＲ５ 的人星形胶质细胞表面。结论：不同嗜性ＨＩＶ－１Ｖ３区结合于细胞表面的能力不同从亲嗜株Ｖ３区直接结合于细胞表面并被其自身所增强，其靶分子至少包括辅助受体 ＣＸＣＲ４和蛋白酶分子；而Ｒ５亲嗜株 ＡＤＡ Ｖ３区则不结合于 ＣＣＲ５和蛋白酶。     

B7/CD28和ICAM-1/LFA-1共刺激信号对T及B细胞功能影响的研究

目的　研究共刺激途径Ｂ７／ＣＤ２８ 和ＩＣＡＭ１／ＬＦＡ１ 对Ｔ 细胞活化以及Ｂ 细胞效应的作用。方法　在体外建立ＡＰＣＴＢ 细胞反应系统, 用Ｂ７１ 单抗和ＩＣＡＭ１ 单抗分别阻断Ｂ７／ＣＤ２８ 和ＩＣＡＭ１／ＬＦＡ１ 共刺激途径, 利用３ ＨＴｄＲ 法检测Ｔ 细胞增殖,ＥＬＩＳＡ 法测定Ｂ 细胞分泌的抗体, 用ＲＴＰＣＲ 法检测细胞因子基因的表达。结果　Ｂ７１ 单抗和ＩＣＡＭ１ 单抗均可抑制Ｔ 细胞增殖及ＩＬ２ 的产生。Ｂ７１ 单抗可下调Ｂ 细胞抗体的产生（ Ｐ＜ ０ ．０５） , 而ＩＣＡＭ１ 单抗未见明显的抑制（ Ｐ＞ ０ ．０５） 。Ｂ７１ 单抗和ＣｓＡ 联用能阻断Ｔ 细胞增殖活性及Ｂ 细胞的效应, 而ＩＣＡＭ１ 单抗和ＣｓＡ联用则无此作用。Ｂ７１ 单抗能下调ＩＬ２ 和ＩＦＮγｍ ＲＮＡ 表达,Ｂ７１ 单抗和ＣｓＡ 联用则阻断ＩＬ２ 和ＩＦＮγｍ ＲＮＡ 表达,ＩＬ４ 和ＩＬ１０ ｍ ＲＮＡ 仍可表达。结论　Ｂ７／ＣＤ２８ 和ＩＣＡＭ１／ＬＦＡ１ 共刺激途径在Ｔ 细胞活化中具有不同的作用,Ｂ７１ 单抗和ＣｓＡ 联用可导致Ｔ 细胞功能失活即无能。     

细胞毒颗粒相关蛋白TIA-1在鼻NK/T细胞淋巴瘤及淋巴增生组织中的表达

目的 观察２７例鼻ＮＫ／Ｔ细胞淋巴瘤之瘤细胞表达细胞毒颗粒相关蛋白ＴＩＡ－１的情况及其与该肿瘤的免疫表型,基因型及ＥＢ病毒感染的关系。方法 采用ＳＰ法免疫组织化学染色,选用的抗体有：ＴＬＡ－１,ＣＤ５６,ＣＤ３ε,ＣＤ４５ＲＯ,ＣＤ８和ＣＤ２０等;聚合酶链反应,作ＴＣＲγ链及免疫球蛋白ＪＨ链基因重排,ＥＢＥＲ１／２原位杂交及与ＴＬＡ－１和ＣＤ８等的双标记染色,还与１０例鼻咽淋巴增生病例进行了比较。     

SDF1基因一个多态位点在中国人群中的分布

关于趋化因子受体与人免疫缺陷病毒（ｈｕｍａｎｉｍｍｕｎｏｄｅｆｉｃｉｅｎｃｙｖｉｒｕｓ，ＨＩＶ）的相关性研究于１９９５年起步，迅速成为当前ＨＩＶ研究热点。１９９６年，Ｏｂｅｒｌｉｎ等［１］和Ｂｌｅｕｌ等［２］发现了基质细胞衍生因子（ｓｔｒｏｍａｌｄｅｒｉｖｅｄｆａｃｔｏｒ１，ＳＤＦ１）作为趋化因子受体ＣＸＣＲ４的配体在ＣＤ＋淋巴细胞和ＨＩＶ１的融合中起作用，它是嗜淋巴细胞ＨＩＶ１株感染的体外潜在抑制因子，可阻断ＨＩＶ１侵入人体的通路。本实验的目的是观察ＳＤＦ１基因多态性在中国不同地区汉族…     

转染B7—1基因至鼻咽癌细胞株及其诱导的细胞免疫应答

通过包装细胞把逆转录病毒载体ｐＬＸＳＮ／Ｂ７－１导入鼻咽癌细胞株ＣＮＥ１，利用ＲＴ－ＰＣＲ及ＦＡＣｓ等技术证实Ｂ７－１的表达情况，同时检测了ＣＮＥ１细胞表面ＭＨＣＩ抗原。在此基础之上，观察了表达Ｂ７－１的ＣＮＥ１细胞（ＣＮＥ１／Ｂ７－１）对健康个体ＰＢＬ（外周血淋巴细胞）的增殖及细胞因子分泌的影响，结果表明：ＣＮＥ１／Ｂ７－１可以促进ＰＢＬ的增殖及细胞因子的分泌，且增高水平的细胞因子主要是ＩＬ－２和ＩＦＮ－γ。提示：ＣＮＥ１／Β７－１诱导的免疫应答以细胞免疫为主。     

淋巴细胞白血病细胞分化与基因重排研究

采用ＭｃＡｂｓ免疫酶和ＰＣＲ技术研究３５例淋巴细胞白血病细胞分化起源及ＩｇＨ和ＴＣＲγ、ζ基因重排。结果表明：２０例表达Ｂ细胞表面标记的病例中，１５例Ｂ－ＡＬＬ分别起源于Ｂ祖、前前Ｂ、前Ｂ和成熟Ｂ细胞，５例Ｂ－ＣＬＬ均起源于成熟Ｂ细胞；１７例检测到ＩｇＨ基因重排，８例伴ＴＣＲｒ基因重排，２例伴ＴＣＲξ基因失。８例Ｔ－ＡＬＬ分别起源于幼稚、普通和成熟胸腺细胞，均检测到ＴＣＲｒ基因重排和／或ＴＣＲξ基     

MRL/lpr Thy1.1小鼠中一个新的T细胞亚群的发现

目的研究ＭＲＬ／ｌｐｒＴｈｙ１．１小鼠中Ｔ细胞的异常、异常Ｔ细胞的起源及其与淋巴腺病理的关系。方法取出生后不同时期ＭＲＬ／ｌｐｒＴｈｙ１．１小鼠及正常Ｃ５７ＢＬ／６小鼠的造血淋巴组织，制备单细胞悬液并用流式细胞技术检测其细胞表面标记，然后以ｔ检验进行统计学处理。结果发现ＭＲＬ／ｌｐｒＴｈｙ１．１小鼠中存在着一个异常的、与淋巴腺病理密切相关的Ｔ细胞亚群，其表型为Ｔｈｙ１．１－ＴＣＲαβ＋Ｌｙ５＋，而且这一细胞亚群随着年龄增长而迅速增加，至１９周龄，其可以占淋巴结细胞总数的８０％。同时，淋巴结及脾脏中传统Ｔ细胞（Ｔｈｙ１．１＋ＴＣＲαβ＋Ｌｙ５－）随着Ｔｈｙ１．１－ＴＣＲαβ＋Ｌｙ５＋细胞的增加而逐渐减少。结果还表明，这一细胞亚群既不在胸腺也不在骨髓中分化成熟，但这一细胞亚群起源于某些异常骨髓造血细胞。结论ＭＲＬ／ｌｐｒＴｈｙ１．１小鼠中存在着一个起源于某些异常骨髓造血细胞的表型为Ｔｈｙ１．１－ＴＣＲαβ＋Ｌｙ５＋的随着年龄增长而迅速增加的Ｔ细胞亚群     

喉癌组织中FEZ1／LZTS1基因的表达及其临床意义

目的：探讨FEZ1／LZTS1基因在喉鳞状细胞癌中的表达缺失及其与临床病理的关系。方法：采用逆转录聚合酶链反应（RT—PCR）法,分析50例原发性喉癌组织和癌旁组织中FEZ1／LZTS1基因的表达情况。结果：FEZ1／LZTS1基因在癌旁组织中表达率明显高于喉癌组织（P〈0．01）;在喉癌组织中FEZ1／LZTS1基因阳性表达率随其病理分级、临床分期升高而降低（P〈0．01）,而与患者年龄、性别和原发灶部位无关。结论：FEZ1／LZTS1基因的表达缺失可能对LSCC的发生发展起重要作用,是LSCC发展中的重要分子事件。     

Glutathione S-transferases M1/T1 gene polymorphisms and endometriosis: a meta-analysis of genetic association studies

In view of the controversies surrounding the glutathione S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed. In this meta-analysis involving 14 GSTM1 studies with 1539 cases and 1805 controls and nine GSTT1 studies with 746 cases and 834 controls, respectively, substantial heterogeneities among studies were found. In addition, asymmetry in funnel plot was evident, which is likely to stem from publication bias, given no apparent indication of true heterogeneity. The bias appears to be prominent for GSTM1 studies, but is less so for GSTT1 studies. After correction for this bias, there is no evidence that women with GSTM1 null genotype have increased risk of developing endometriosis as compared with women with other genotypes. For GSTT1, the risk associated with the null genotype is 29% higher than other genotypes. However, even this estimate should be viewed with a large grain of salt, because the estimate could easily lose its statistical significance if there is a realistic 69-80% publication probability.     

Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human lymph nodes

Monoclonal antibodies specific for the adhesion molecules participating in lymphocyte homing, lymphocyte function associated antigen-1 (LFA-1) and very late antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), were used to characterize their expression pattern in human lymph nodes by immunohistochemical and immunoelectron microscopic techniques. The location of LFA-1-positive lymphocytes and selective expression of ICAM-1 on the luminal plasma membrane of high endothelial venule endothelium suggested that the LFA-1/ICAM-1 adhesion pathway participates only in the initial step of the lymphocyte migration process. Lymphocytes passing through endothelium appear not to be influenced by this pathway. VCAM-1 was detected occasionally on the endothelium of high endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in peripheral lymph nodes. VLA4-positive lymphocytes tended to be more frequently observed within high endothelial venules in mesenteric lymph nodes than in peripheral ones. Strong expression of both ligands, ICAM-1 and VCAM-1, was noted on the plasma membrane of follicular dendritic cells, and was especially prominent on their labyrinthine folding, and on the interdigitating cells in the paracortex. Furthermore, both LFA-1-and VLA4-positive lymphocytes localized around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways play an important role in the lymphocyte recognition of antigen-presenting cells.     

Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It has been demonstrated that the CYP1A1 metabolizes not only environmental chemicals but also estrogens, and glutathione-S-transferases (GSTs) are detoxification enzymes that protect cells from toxicants by conjugation with glutathione. In this study, to investigate the association of CYP1A1 (MspI), GSTM1 and GSTT1 polymorphisms with hypospadias, a case-control study of 31 case mothers who had boys with hypospadias and 64 control mothers was performed in Japan. These polymorphisms were investigated by PCR-based methods using DNA from peripheral lymphocytes. We found that the heterozygous CYP1A1 and heterozygous and homozygous CYP1A1 were less frequent in the case mothers than in the control mothers [adjusted odds ratio (OR)=0.17, 95% confidence interval (CI)=0.04-0.74, OR = 0.28, 95% CI = 0.08-0.97, respectively]. We found no effect of maternal smoking on the hypospadias risks among the gene polymorphisms. The results suggest that mothers with the CYP1A1 MspI variant allele may have a decreased risk for hypospadias.     

Th1/Th2、Tc1/Tc2亚群在乙肝肝硬化患者中的作用

目的 :探讨乙肝肝硬化患者外周血 (PBMC)中CD4 和CD8 T细胞内Th1和Th2类细胞的平衡状态 ,探明Th1、Th2类细胞在乙肝肝硬化中的作用。方法 :乙肝肝硬化患者CD4 T细胞和CD8 T细胞中IFN γ 和IL 4 细胞的百分率 ,观察乙肝肝硬化患者Th1 Th2、Tc1 Tc2比例的变化。结果 :乙肝肝硬化患者PBMC中CD4 ,CD8细胞 ,CD4 CD8比值与健康对照者相比无统计学差异 (P >0 0 5 ) ,Th1细胞及Tc1细胞百分率为 8 8% ,9 0 % ,较健康对照者 7 5 % ,7 7%升高 (P <0 0 5 )。结论 :乙肝肝硬化患者外周血T细胞亚群发生Th1类偏移 ,在乙肝肝硬化的发生和发展中可能起重要作用     

DNA damage and p21WAF1/CIP1/SDI1 in experimental injury of the rat adrenal cortex and trauma-associated damage of the human adrenal cortex

In vivo models are needed to study the reactions of tissues to DNA damage, such as the induction of the cyclin-dependent kinase inhibitor p21, indicating potential repair of the damage, versus apoptosis, indicating the elimination of the damaged cells. Damage to DNA occurs in tissues during shock, sepsis, and other critical medical conditions. Previous studies have found evidence of damage to the cortex of adrenal glands from organ donors who had undergone severe trauma prior to death. The present experiment studied rats under experimental interventions of clinical relevance to patients with conditions that put them at risk for damage to the adrenal glands. These interventions comprised ischaemia and reperfusion injury, sepsis following caecal ligation and puncture, acute pancreatitis, and administration of chemical agents (zymosan and acrylonitrile). All the interventions caused an increase in p21 mRNA as assessed by northern blotting and in situ hybridization. Increased nuclear p21 protein was shown by immunohistochemistry. All the interventions caused damage to DNA, as shown by labelling of available 3′ termini of single-strand breaks with terminal transferase. The number of cells undergoing apoptosis, visualized by ligation of a hairpin oligonucleotide probe to double-strand breaks in DNA, was much lower. In rat adrenal glands, apoptotic cells were infrequent under all the conditions studied. They were more abundant in human organ donor adrenal glands that were previously shown to have extensive DNA damage accompanied by induction of p21. The similarity of the effects of a wide variety of surgical interventions and chemical agents suggest a common pathophysiological mechanism which is not specific to the initiating injury. Experimental injury of the rat adrenal cortex provides a model for investigating the role of organ DNA damage and of mediators of the response to DNA damage, such as p21. Copyright © 1999 John Wiley & Sons, Ltd.     

鹅流感病毒2/96-H5N1亚型毒株RNA1-3及RNA5节段核苷酸全序测定

目的　明确广东鹅流感病毒２９６Ｈ５ Ｎ１ 亚型毒株ＲＮＡ１３ 和ＲＮＡ５ 节段核苷酸全序列及其所编码蛋白的氨基酸序列,以及这些基因节段与香港禽流感病毒１５６９７Ｈ５ Ｎ１ 亚型毒株相应节段间的关系。方法　病毒粒ＲＮＡ经逆转录合成ｃＤＮＡ,经聚合酶链反应（ＰＣＲ） 扩增,产物纯化,采用双脱氧链末端终止法进行核苷酸序列测定。结果　广东鹅流感病毒２９６Ｈ５ Ｎ１ 亚型毒株ＲＮＡ１３ 和ＲＮＡ５ 节段长度分别为２３４１,２ ３４１ ,２ ２３３ 和１５６５ 个核苷酸。它们分别编码ＰＢ２（ 含７５９ 个氨基酸）,ＰＢ１（ 含７５７个氨基酸） ,ＰＡ（ 含７１６ 个氨基酸） 和ＮＰ蛋白（ 含４９８ 个核苷酸） 。这些蛋白与香港禽流感病毒１５６９７Ｈ５ Ｎ１ 亚型毒株相应蛋白氨基酸序列的同源性分别为９６－４％ ,９７－２％ ,９７－３ ％ 和９７－０％ 。结论　本毒株ＲＮＡ１３ 和ＲＮＡ５ 节段长度分别为２ ３４１,２ ３４１,２ ２３３ 和１ ５６５ 个核苷酸,它们与香港１５６９７Ｈ５ Ｎ１ 亚型毒株间存在着差异