人脐血T、B淋巴细胞和NK细胞的免疫学表达特性

目的 探讨人脐血T、B淋巴细胞和NK细胞，以及T／NK细胞杀伤性抑制性受体（KIR）表达的免疫学特性及其意义。方法 应用流式细胞仪检测26例正常新生儿脐血的T、B淋巴细胞和NK细胞抗原标记，包括CD45RA、CD45RO、CD69、CD25、CD40L、CD40、CD10、CD20和CD16等抗原的表达，以及脐血T／NK细胞上KIR分子（CD158a和CD158b抗原）的表达，并与正常儿童外周血比较。结果 脐血T淋巴细胞中CD45RA^ 细胞表达高于外周血（P＜0．01），CD45RO^ 则明显低于外周血（P＜0．01）；脐血T细胞CD69表达极低；CD25在CD8^ 细胞亚群中几乎不表达；CD40L在脐血T细胞中表达低于外周血（P＜0．05）。脐血B淋巴细胞中不成熟亚群CD10^ ／CD19^ 比例增高，成熟B细胞表型CD19、CD20、CD40等抗原均明显高于正常外周血（P＜0．01）。脐血中T淋巴细胞和NK细胞均存在KIR分子表达；脐血和外周血中T淋巴细胞CD158分子表达低于NK细胞（P＜0．01），脐血T淋巴细胞亚群中CD158分子表达低于正常外周血；CD158几乎不表达于CD4^ T细胞，主要表达于CD8^ T细胞，且以CD158a^ 为主；脐血中NK细胞CD158分子表达高于T淋巴细胞（P＜0．05），但明显低于外周血NK细胞KIR的表达（P＜0．01）。结论 脐血T淋巴细胞包括原始和早期T细胞以及T细胞受体表达障碍，导致脐血T淋巴细胞免疫功能不成熟，可能是脐血移植（UCBT）后移植物抗宿主病（GVHD）发生率低和程度轻的重要原因之一。脐血B淋巴细胞免疫应答障碍可能缘于T淋巴细胞表型或功能的障碍。脐血T／NK细胞KIR的表达特性提示，KIR可能与UCBT中GVHD和移植物抗白血病（GVL）效应有关。     

脐血T淋巴细胞及其亚群低剂量辐射效应研究

目的　观察脐血T淋巴细胞及其亚群低剂量辐射 (LDR)效应。方法　对脐血T淋巴细胞及其亚群分离、培养 ,LDR后用3 H 胸腺嘧啶核苷 (3 H TdR)掺入法观察其DNA合成和抗肿瘤细胞K562 活性 ,集落培养观察脐血干细胞造血能力。结果　脐血T淋巴细胞及其亚群CD4、CD8、CD19细胞经 2、5、10、2 0cGy的LDR与 0cGy(对照组 )比较 ,3 H TdR掺入明显增加 ,5cGy的LDR与 0cGy比较 ,3 H TdR掺入分别为 14 3 2 %、14 6 8%、14 5 4 %、15 7 9%。对K562 细胞杀伤作用经 2、5、10、2 0cGy的LDR均有明显增高 ,5cGy的LDR与 0cGy比较杀伤率和NK相对活性分别为 38 3%和 172 0 %。造血干细胞集落数无差别 ,5cGy的LDR与 0cGy比较分别为 12 2和 12 1个。结论　适宜的LDR对脐血T淋巴细胞和亚群的DNA合成有刺激作用 ,能增加体外抗肿瘤细胞K562活性 ,并保持脐血干细胞造血能力     

激活脐血单个核细胞体外抗白血病细胞株活性研究

目的：探讨植物血凝素(PHA)、白细胞介素-2(IL-2)、抗CD3单克隆抗体(αCD3Ab)激活的脐血单个核细胞(CBMC)体外对K562的杀伤活性,以及外源性刺激因子对CBMC的可溶性白细胞介素-2受体(sIL-2R)含量的影响。方法：采集CBMC分别与不同刺激因子体外短期培养,台盼蓝拒染法测效应细胞的增殖能力,ELISA法检测上清液中sIL-2R的含量, 3 H-TdR释放法测定效应细胞体外对K562靶细胞的杀伤活性。结果：脐血PHA-CD3AK细胞在体外培养3 d后增殖倍数、活化后上清液中sIL-2R的含量显著高于PHA-LAK,CD3AK和LAK细胞(P<0.05)。PHA-CD3AK细胞体外对白血病细胞株K562细胞的细胞毒活性明显高于PHA-LAK,CD3AK和LAK细胞(P<0.05)。结论：脐血单个核细胞经PHA,IL-2和αCD3Ab激活后,可有效形成PHA-CD3AK效应细胞,其增殖活性、细胞毒性均高于PHA-LAK,CD3AK和LAK细胞。     

IL-4基因修饰增强脑胶质瘤细胞毒性T淋巴细胞杀伤活性机制的探讨

目的 进一步探讨白细胞介素4（IL－4）基因修饰瘤苗增强细胞毒性T淋巴细胞（CTL）杀伤活性的机制。方法 通过逆转录病毒载体PL－IL－4－SN将人IL－4基因导入神经胶质瘤系SHG44细胞，以IL－4基因修饰瘤苗和野生型瘤细胞作刺激细胞诱导CTL反应，通过流式细胞仪检查瘤细胞表面分子的表达。结果 （1）IL－4基因修饰诱导瘤细胞表达MHC－Ⅱ类抗原、B7－1及ICAM－1等免疫刺激分子，对MHC－I类抗原表达无影响，其瘤苗诱导的CTL杀伤活性为野生型瘤细胞的7倍（P＜0．01）。（2）加入抗IL－4单抗可完全阻断IL－4诱导的细胞表面分子的表达，IL－4基因修饰瘤苗诱导CTL反应时培养上清可检测到大量IL－2的产生。抗IL－4或抗细胞表面分子单抗可降低IL－2产生及抑制CTL反应。结论 IL－4基因修饰可能是通过诱导MHC－Ⅱ类抗原等表面分子表达，促进IL－2的产生从而增强CTL杀伤活性。     

病毒性肺炎患儿自然杀伤细胞亚群、T细胞亚群及血IL-2、IL-4、INF-γ变化的研究

目的 探讨病毒性肺炎患儿自然杀伤(NK)细胞亚群、T细胞亚群及血IL-2、IL-4、INF-γ的动态变化及临床意义.方法 采用流式细胞术测定32例病毒性肺炎患儿急性期(肺炎起病2?d内)、恢复期(肺炎起病5?d内)外周血NK细胞亚群、T细胞亚群,用ELISA法测定血IL-2、IL-4、INF-γ水平,用乳酸脱氢酶释放法测定NK细胞活性变化,并与30例健康对照组儿童进行比较.结果 (1) 病毒性肺炎患儿CD16+CD56+、CD16+NK细胞在急性期分别为(0.73±0.17)%、(0.39±0.2)%,恢复期分别为(1.47±0.22)%、(0.89±0.14)%;急性期与恢复期比较,恢复期CD16+CD56+、CD16+NK细胞明显升高(P<0.01),但均显著低于对照组(P<0.01).两组NK细胞亚群变化与其活性改变呈正相关.病毒性肺炎患儿CD56+NK细胞与健康儿童差异无显著性(P>0.05).(2) 与对照组相比,病毒性肺炎患儿的急性期、恢复期IL-2、IL-4均无明显改变,差异无显著性(P>0.05);急性期INF-γ无明显改变,差异无显著性(P>0.05),而恢复期INF-γ[(28.10±1.38)?μg/L]明显高于急性期[(22.78±1.19)?μg/L],差异有非常显著性(P<0.01).(3) 与对照组相比,病毒性肺炎患儿CD4+、CD4+/CD8+T细胞计数在急性期与恢复期均无明显改变,差异无显著性(P>0.05).病毒性肺炎急性期、恢复期CD8+T细胞均低于对照组,差异有显著性(P<0.05),但病毒性肺炎急性期、恢复期间差异无显著性(P>0.05).结论 病毒性肺炎患儿NK细胞活性降低,活性与亚群数目呈正相关;病毒性肺炎患儿抑制性T细胞功能低下.病毒性肺炎急性期NK细胞激活是多因素共同作用的结果 .     

支原体肺炎患儿自然杀伤细胞和细胞毒性T淋巴细胞检测及分析

支原体肺炎是儿科常见的呼吸道感染性疾病,它的发病机理目前认为除了病原体直接侵害外,还与免疫功能紊乱有关。自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）为机体重要的免疫细胞。为了探讨肺炎支原体感染过程中的细胞免疫反应,对2002年10月～2003年6月我院住院的17例肺炎支原体肺炎患儿的NK和CTL进行了检测与分析,现报告如下。     

过敏性紫癜患儿急性期细胞免疫功能变化

目的 研究过敏性紫癜患儿急性期外周血淋巴细胞免疫的变化及其临床意义。方法 采用流式细胞术(FCM)对23例过敏性紫癜急性期患儿外周血淋巴细胞及其亚群：CD3^ 、CD4^ 、CD8^ 、CD19^ 、CD16 56^ 进行定量检测，并用^3H—TdR标记法测定非杀伤(NK)细胞活性。结果 过敏性紫癜急性期患儿外周血CD4^ ,CD4^ /CD8^ ,CD16 56^ 、NK细胞活性均显著低于健康对照组(P＜0.01)，而CD8^ 活性显著升高(P＜0．05)，CD19^ 显著升高(P＜0.01)，均有统计学意义，CD3^ 稍升高，无明显差异(P＞0．05)。结论 过敏性紫癜患儿急性期存在细胞免疫功能失调，主要表现在T细胞亚群紊乱，B细胞呈多克隆活化，NK细胞数量及活性降低。     

不同方式刺激脐血树突状细胞对细胞因子诱导杀伤细胞和自然杀伤细胞杀伤活性的影响

目前对造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后残留肿瘤细胞的清除需通过过继免疫治疗等手段来解决.通过特定细胞因子联合扩增脐血中细胞因子诱导杀伤(cytokine-induced killer,CIK) 细胞、自然杀伤(natural killer,NK)细胞,可增强脐血移植(UCBT)后的移植物抗白血病(graft-versus-leukemia,GVL)效应.树突状细胞(dendritic cells ,DC)在免疫应答的诱导中具有独特地位,     

缺氧缺血性脑病新生儿自然杀伤细胞与T细胞亚群的变化及其相关因素

目的了解缺氧缺血性脑病(HIE)新生儿自然杀伤(NK)细胞及T细胞亚群的变化,观察其与各种因素的相关性。方法应用流式细胞仪测定50例HIE和20例正常新生儿血NK细胞、CD3 、CD4 、CD8 细胞及CD4 /CD8 比值。结果HIE患儿NK细胞和T细胞亚群的表达均明显低于正常新生儿(P均<0.05);中、重度HIE患儿NK细胞和CD3 、CD4 细胞及CD4 /CD8 比值明显均低于轻度HIE(P均<0.05),而不同分度HIE的CD8 细胞则无统计学差异(P均>0.05);NK细胞、CD3 、CD4 及CD4 /CD8 与HIE病情分度均呈负相关(P均<0.05)。NK细胞表达与胎龄呈正相关;CD3 细胞与羊水污染呈负相关(P<0.05);CD4 细胞与羊水污染呈负相关,与出生体质量和Apgar评分呈正相关(P<0.05);CD4 /CD8 比值与分娩方式存在线性相关(P<0.05)。结论缺氧缺血可导致HIE患儿NK细胞活性抑制及T淋巴细胞亚群紊乱,某些因素对细胞免疫功能有一定影响。     

自然杀伤细胞与丙型肝炎病毒感染的Huh7.5细胞体外共培养后的功能变化

目的探讨体外丙型肝炎病毒(HCV)感染对NK细胞功能产生的影响及其可能的机制。方法利用质粒JC1-Flag2体外转录得到的HCV感染性颗粒(HCVcc)以MOI4.8感染Huh7.5细胞(Huh7.5-HCVcc),与健康人外周血分离得到的NK细胞进行共培养。与Huh7.5-HCVcc细胞共培养前后,采用ELISA法和MTT比色法分别检测NK分泌细胞因子IFN-γ、TNF-α和IL-10的水平和细胞杀伤活性,以评估HCV感染对NK细胞功能的影响。结果与MOI4.8的Huh7.5-HCVcc细胞共培养,NK细胞分泌IFN-γ、TNF-α和IL-10水平受到抑制,其中IFN-γ在共培养6 h(P0.001)、9 h(P0.001)、12 h(P0.001)受到显著抑制,TNF-α在共培养6 h(P0.001)、9 h(P0.001)、12 h(P=0.001)受到显著抑制,IL-10在共培养6 h(P0.001)、9 h(P=0.006)受到显著抑制;且NK细胞分泌细胞因子IFN-γ、TNF-α和IL-10的功能均在共培养6 h受到的抑制效应最大,平均抑制率分别为24.1%、20.7%和24.3%。NK细胞杀伤活性在共培养6 h(P=0.023)受到抑制,平均抑制率为16.6%。结论在体外与MOI4.8的Huh7.5-HCVcc细胞共培养,NK细胞分泌细胞因子(IFN-γ、TNF-α和IL-10)和细胞杀伤功能均受到抑制,且在不同时间点受到的抑制程度不同,提示NK细胞在HCV感染的不同阶段可能起到不同的作用。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.