Immune reconstitution in children following chemotherapy for haematological malignancies: a long-term follow-up

Modern intensive chemotherapy for childhood haematological malignancies has led to high cure rates, but has detrimental effects on the immune system. There is little knowledge concerning long-term recovery of the adaptive immune system. Here we studied the long-term reconstitution of the adaptive immune system in 31 children treated for haematological malignancies between July 2000 and October 2006. We performed detailed phenotypical and functional analyses of the various B and T cell subpopulations until 5 years after chemotherapy. We show that recovery of newly-developed transitional B cells and naive B and T cells occurred rapidly, within months, whereas recovery of the different memory B and T cell subpopulations was slower and incomplete, even after 5 years post-chemotherapy. The speed of B and T cell recovery was age-independent, despite a significant contribution of the thymus to T cell recovery. Plasmablast B cell levels remained above normal and immunoglobulin levels normalised within 1 week. Functional T cell responses were normal, even within the first year post-chemotherapy. This study shows that after intensive chemotherapy for haematological malignancies in children, numbers of several memory B and T cell subpopulations were decreased on the long term, while functional T cell responses were not compromised.     

血管紧张素Ⅱ和Ⅳ对心血管系统的共同调节

肾素血管紧张素系统(RAS)是心血管疾病的主要调节因素,其核心成分血管紧张素Ⅱ(AngⅡ)不仅可以直接收缩血管、调节血压,还与炎症、内皮细胞功能失调、动脉粥样硬化、高血压、心力衰竭等疾病密切相关。以前大多数研究集中于AngⅡ的功能,以此为靶点生产的AT1受体抑制剂及血管紧张素转换酶Ⅰ抑制剂在心血管疾病的临床治疗中发挥了重要的作用。但是近年来的研究发现,RAS其他成员如Ang(1-7)、AngⅣ有着各自独立的生物学效应,这提示RAS是一个远比我们以往认识     

肺表面活性物质对哮喘T细胞亚群细胞周期及其调节蛋白的影响

目的观察肺表面活性物质（PS）对发作期哮喘患者T细胞亚群细胞周期及其调节蛋白的影响,揭示PS对CD4＋、CD8＋T细胞增殖周期的具体作用机制及其在哮喘治疗中的意义。方法利用细胞培养技术,通过体外PS干预,流式细胞仪测定经PS干预和未经PS干预的CD4＋、CD8＋T细胞的细胞周期分布和CD4＋、CD8＋T细胞内细胞周期调节蛋白p27kip1、cyclinE、cyclinA、cyclinB的表达水平。结果哮喘患者CD4＋、CD8＋T细胞分别与PS体外共同培养后,加PS组的S期、G2/M期的CD4＋T比例显著低于对照组（P〈0.01）;G0/G1期的CD4＋T细胞比例显著高于对照组（P〈0.01）。加PS组的S期CD8＋T比例显著低于对照组（P〈0.01）;G2期的CD8＋T细胞比例略低于对照组,但差异无统计学意义（P〉0.05）;G0/G1期的CD8＋T细胞比例高于对照组（P〈0.05）。CD4＋T细胞内p27kip1的表达水平高于对照组（P〈0.05）;CD4＋T细胞内cyclinE表达水平显著低于对照组（P〈0.01）;CD4＋T细胞内cyclinA、cyclinB的表达水平低于对照组（P〈0.05）。CD8＋T细胞内p27kip1的表达水平高于对照组（P〈0.05）;CD8＋T细胞内cyclinE、cyclinA表达水平低于对照组（P〈0.01）;CD8＋T细胞内cyclinB的表达水平与对照组差异无统计学意义（P〉0.05）。结论 PS通过抑制CD4＋T细胞的正性细胞周期调节蛋白cyclinE、cyclinA、cyclinB的表达和上调其负性细胞周期调节蛋白p27kip1的表达,抑制CD4＋T细胞的DNA合成和细胞分裂,进而抑制CD4＋T细胞增殖;通过下调CD8＋T细胞内cyclinE、cyclinA的表达,上调p27kip1的表达,抑制CD8＋T细胞DNA合成。     

Serum and Peritoneal Fluid Cytokine Profiles in Infertile Women with Endometriosis

Background: Endometriosis is a chronic inflammatory disease with the growth of endometrial cells out of uterus and in the peritoneal cavity. T cell subsets participate in the establishment and progress of the disease by producing different cytokines. Objective: To investigate a group of cytokines related to Th1/Th2/Th17/Treg subsets within both peripheral blood and peritoneal fluid (PF) samples from infertile endometriosis women. Methods: Peripheral blood and PF samples were collected from 30 infertile endometriosis and 30 non-endometriosis fertile women during laparoscopy. Concentration of cytokines, including TNF-α, IFN-γ, TGF-β1, IL-4, IL-10, IL-17 and IL- 23 were evaluated using ELISA method. Results: Results indicated that the concentration of IFN-γ within serum was significantly reduced in endometriosis group (p=0.001). Regarding PF cytokines, TGF-β1 was increased in endometriosis group (p=0.030). Furthermore, the ratios of IFN-γ/TGF-β1 and IL-17/IL-23 were significantly different between endometriosis and non-endometriosis women in serum samples (pConclusion: Based on the results of the present study, in women with endometriosis, the disturbance of cytokines network might gradually activate the inflammatory responses and tissue repair, resulting in endometriosis development after several years.     

小儿轮状病毒肠炎肠道外脏器损伤及免疫状态研究

Objective To evaluate the parenteral complications and their risk factors and to study the immune status by detecting immunoglobulin and lymphocyte subsets in children with rotavirus enteritis. Methods Sixty-four children with rotavirus enteritis who were treated in Shengjing Hospital of China Medical University between January 2007 and December 2008(observation group) and 18 healthy chiIdren for health screening at pediatric health care center (normal control group) were reeruimd.Clinical manifestations were collected,stool specimens were detected for rotavirus using ELISA,lymphocyte subsets were detected using flow cytometer,and immunoglobulin.liver enzyme and myocardial enzyme were detected.Results Rotavirus enteritis may be complicated by parenteral complications(liver,myocardium,respiratory and nervous system).The activity of ALT,AST,LDH,CK and CK-mB were higher in observation group than that in normal control group(P<0.05).In observation group,liver injury rate in children younger than 12 months was higher than that in children older than 12 months,and the activity of CK and CK-mB were highcr in severe diarrhea cases[CK(324.5±995.5)U／dl,CK-mB(93.8 4±61.5)U／dl]than that in mild diarrhea cases [CK(252.8±130.4)U／dl,CK.mB(59.6±32.6)U／dl](P<0.05).The level of IgG was lower in observation group[(4.46±1.56)g／L]than that in control group[(5.80±1.67)g／L](P<0.05).Lymphocytes subsets study revealed that the activity of CD4+ in observation group[(29.0±4.18)％]was lower than that in control group[(38.6±3.97)％](P<0.05),the activity of CDl9+ [(38.8±3.94)％]was higher than that in control group[(23.1±7.70)％](P<0.05)and the CD4+／CD8+ ratio was reverse in observafion group.Conclusion Rotavirus enteritis may be complicated by parenteral injuries which get liver,myocardium,respiratory and nervous system involved.Children with rotavirus enteritis Call lead to low immune function.Determination of liver enzyme,myocardial enzyme,immunoglobulin and lymphocyte subsets has important clinical significance to monitoring the change of condition and guiding treatment.     

EB病毒相关性噬血细胞综合征的临床特征及外周血淋巴细胞亚群的变化

目的 分析EB病毒相关性噬血细胞综合征(EBV-AHS)患儿的临床特点,了解其外周血淋巴细胞亚群的变化.方法 20例EBV-AHS患儿,均符合噬血细胞综合征的诊断标准,并有EBV感染的证据,对其临床特点进行总结分析,并采用流式细胞术检测外周血淋巴细胞亚群CD4+、CD8+、CD19+、CD16+CD56+、CD4+/CD8+的水平.选择20例健康儿童作为对照组.结果 在EBV-AHS的诊断标准中,以发热、血常规2系以上降低、乳酸脱氢酶升高(＞1 000 U/L)、高密度脂蛋白降低及铁蛋白增高(＞1 500 g/L)5项指标异常发生率最高,均为100%.与对照组相比,EBV-AHS患儿外周血CD8+T及CD19+B细胞比例增高(分别为53.70% ±10.6% vs 27.05% ±8.22%,24.95% ±5.34% vs11.85% ±4.53%),而CD4+T及CD16+CD56+NK细胞比例下降(分别为23.60% ±6.42% vs 45.20% ±5.74%,5.55% ±2.87% vs 14.70% ±4.16%),CD4+/CD8+比值降低(0.46±0.16 vs 1.84±0.68),差异均有显著性(P＜0.01).结论 EBV-AHS患儿细胞及体液免疫功能发生紊乱,导致了疾病的发生发展.     

类风湿性关节炎患者外周血T淋巴细胞Ag-NORs及T亚群的变化

目的探讨外周血T淋巴细胞A g-NOR s及T亚群在类风湿性关节炎中的应用价值。方法32例类风湿性关节炎患者,17例病人处于活动期,15例经治疗后处于缓解期。36例健康体检者作为对照。分别检测外周血T淋巴细胞A g-NOR s、T亚群(CD3 、CD4 、CD8 ),计算CD4 /CD8 比值。结果与对照组相比,RA病人活动期T淋巴细胞A g-NOR s、CD4 细胞、CD4 /CD8 比值均升高(P<0.05),而CD8 细胞降低(P<0.05)。RA缓解期T淋巴细胞A g-NOR s、CD4 细胞、CD4 /CD8 比值较活动期下降(P<0.05),CD8 细胞较活动期升高(P<0.05),与对照组相比均无显著性差异(P>0.05)。CD3 T细胞在RA活动期、缓解期中与对照组相比均无显著性差异(P>0.05)。T淋巴细胞A g-NOR s与CD3 、CD4 、CD8 细胞和CD4 4/CD8 比值之间相关系数均小于0.3(P>0.05),无相关性。结论外周血T淋巴细胞A g-NOR s含量、T细胞亚群分析与RA的发生、发展、治疗有一定关系,结合二者,在观察RA患者的机体免疫状态、疗效方面有一定意义。     

HIV-1感染者CD4＋T淋巴细胞及其各亚群细胞增殖和消亡情况的观察

目的探讨艾滋病病毒I型（HIV-1）感染者CD4＋T淋巴细胞（CD4细胞）及其各细胞亚群：纯真细胞（TN）、中心记忆细胞（TCM）和效应记忆细胞（TEEM）的增殖和消亡情况。方法观察23例未经抗病毒治疗、感染时间大于12个月的HIV-1感染者,以16例健康者为对照,通过流式细胞仪分析CDtT淋巴细胞CD45RO和CD2,的表达情况,把CD4细胞分为TN（CD45RO—CD27＋）、TM（CD45RO＋CD27＋）和TEM（CD45RO＋CD27-）三个亚群。以Ki-67抗原的表达代表细胞的增殖,AnnexinV检测阳性代表细胞的消亡,比较HIV-1感染组和健康组CD4细胞及其各个亚群增殖和消亡的情况。结果健康组（n-16例）CD4细胞增殖率为（O．36±0．24）％,各亚群增殖率分别为Tw（O．07士0．05）％,TcM（O．57±0．52）％和TEM（O．40±0．39）％;CD4细胞消亡率为（6．30土2．41）％,各亚群消亡率分别为TN（4．43士2．21）％,1rcM（6．58±2．50）％和T巳Ⅵ（12．47--4-8．98）％;与之相比,HIV-1感染组（n=23例）：CD4细胞增殖率为（2．93±2．72）％（z=-4．511,P=0．000）,各亚群增殖率：TN（0．524-0．42）％（z=-4．785,P=0．000）,TcM（5．55±5．07）％（z=--4．241,P=0．000）和TEM（4．53±5．20）％（z=-3．884,P=0．000）;CD4细胞消亡率为（23．59±16．27）％（z=-3．883,P=0．000）,各亚群消亡率：TN（17．25±15．80）％（z=-2．227,P=0．026）,TcM（25．16±16．55）％（z=-3．940,P-0．000）,TEM（29．56±16．77）％（z=-3．626,P=0．000）。与健康组相比,HIV-1感染组CD4及其各细胞亚群增殖率和消亡率明显增加,差异有统计学意义。结论与健康组相比,HIV-1感染者CD4细胞及其各个亚群细胞消亡和增殖有明显增加,细胞进入高速更新的状态,纯真细胞亚群和记忆细胞亚群组成比没有明显变化。     

老年持续性腹膜透析患者外周血及腹膜透析流出液辅助性T淋巴细胞亚群分析

目的观察老年维持性腹膜透析患者外周血及腹膜透析流出液中辅助性T细胞亚群的分布情况。方法选取长海医院腹膜透析中心60岁及以上稳定透析16例患者为研究对象（老年实验组）,同一中心稳定透析且一般营养状态、合并症匹配的60岁以下患者16例为对照（对照组）,取外周血及腹膜透析流出液为标本,分离单个核细胞,流式细胞术检测Thelp1、Thelp2、Thelp17及调节性T细胞比例。结果老年实验组外周血中,Th1、Th17细胞比例均降低,分别为（34．2±14．5）％和（1．9±0．6）％,与对照组（38．1±10．7）％,（4．3±2．1）％比较略有降低,但没有统计学意义;Th2、Treg细胞比例咀显升高,分别为（3．2±1．5）％相比于（1．9±1．2）％（P=-0．033）,（7．3±2．9）％相比于（4．3±2．1）％（P=0．028）,差异均有统计学意义。腹膜透析流出液情况类似,除Th2无统计学意义外,Th1、Th17、Treg细胞亚群在老年组中比例分别为（24．2±11．8）％、（3．2±1．8）％和（8．2±4．3）％,对照组为（30．7±19．2）％、（6．7±2．9）％和（5．9±3．9）％,同比变化明显,P值分别为0．031、0．047和O．022,均有统计学意义。结论老年长期连续性不卧床腹膜透析患者机体细胞免疫功能明显下降、宿主免疫功能紊乱,需要通过更细致的营养、疾病评估以明确是否同年龄因素相关。