HCV NS3诱导小鼠特异性T细胞反应的抗原多肽序列筛选

目的 筛选HCV NS3的小鼠T细胞表位多肽序列.方法 BALB/c小鼠用HCV NS3加po-ly （I∶C）或CpG ODN及Montanide ISA720佐剂免疫后,分离其脾淋巴细胞,以覆盖HCV NS3全基因的合成重叠多肽组成的不同多肽库进行刺激,以ELISPOT及流式细胞术检测分泌干扰素γ（IFN-γ）的细胞数及CD8＋/IFN-γ＋细胞或CD4 ＋/IFN-γ＋细胞百分比,确定抗原性最强的多肽库,找出HCV NS3的小鼠T细胞表位多肽.结果 通过ELISPOT及流式细胞术检测,能够刺激淋巴细胞分泌IFN-γ最多及CD8 ＋/IFN-γ＋细胞或CD4＋/IFN-γ＋细胞百分比最高的多肽被选出作为阳性多肽,其中的一个多肽经进一步的ELISPOT及流式细胞术检测确认,其序列为GGCSGGAYDⅢCDECHS.结论 HCV NS3小鼠T细胞表位序列的确定为HCV疫苗的研究打下了基础.     

The clinical utility of inhibiting CD28-mediated costimulation

Summary:  This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.     

HBsAg-vectored vaccines simultaneously deliver CTL responses to protective epitopes from multiple viral pathogens

We have previously demonstrated that the potent immunogenicity of hepatitis B surface antigen (HBsAg) may be exploited to deliver foreign antigens for cytotoxic T-lymphocyte (CTL) induction. Here we demonstrate that a single low-dose immunization with rHBsAg DNA is sufficient to prime for CTL responses against encoded foreign epitope and that the responses may be recalled many months after immunization. We show that simultaneous disease-protective CTL responses restricted through a diversity of MHC class I haplotypes are elicited by recombinant (r) HBsAg DNA containing multiple viral epitopes appended as a C′-terminal polyepitope or encoded individually within the HBsAg polypeptide. CTL responses delivered by rHBsAg DNA were elicited in the presence of HBsAg-directed antibody. These studies vindicate the use of HBsAg as a powerful vector to deliver CTL responses to foreign antigen and have implications for a multidisease vaccine applicable to an MHC-polymorphic population.     

Ipilimumab in non-small cell lung cancer and small-cell lung cancer: new knowledge on a new therapeutic strategy

The challenge of finding a lasting cure for autoimmune disease(s) has not been met. Although the use of systemic anti-inflammatory agents still dominates the treatment of these diseases, there is a push towards developing novel and more specific strategies. In addressing autoimmunity, there is the intrinsic need to understand the mechanisms that lead to the development and maintenance of immunological tolerance to self-antigens. Experimental evidence has shown that directed antigen expression in the thymus can induce immunological tolerance to that antigen. This forms the cornerstone of one strategy directed towards the cure of autoimmunity. In this strategy, individuals with autoimmune disease are transplanted with bone marrow stem cells that have been genetically modified and in this way allow expression of the self-antigen in the thymus.     

慢性淋巴细胞白血病外周血T细胞亚群及免疫球蛋白研究

 目的　分析慢性淋巴细胞白血病（CLL）患者的免疫状态及其与疾病分期的关系。方法　应用流式细胞术（FCM）分析60例B-CLL患者外周血T淋巴细胞亚群的变化，用免疫速率比浊法分析其中37例患者血清中IgG、IgA和IgM的变化，比较各Binet分期患者免疫功能的变化。结果　与正常对照组相比，60例B-CLL患者外周血中CD+3、CD+4和CD+8细胞比率均明显降低（P＜0.01），Binet B、C期组患者CD+4／CD+8比值也明显低于Binet A和正常对照组（P＜0.01）。37例B-CLL患者中有21例患者（56.8 %）出现有免疫球蛋白（Ig）减低的情况。Binet C期组Ig减低发生率高于Binet A和B期（P＜0.05），Binet C期组IgG、IgA、IgM的平均水平明显低于Binet A和B期组（P＜0.05）。结论　CLL患者存在细胞免疫和体液免疫功能的低下，与CLL病程密切相关。检测CLL患者外周血T细胞亚群及Ig水平的变化，对了解CLL免疫功能状态，从而判断病情具有重要作用。     

维甲酸对DENA诱发肝癌大鼠的T淋巴细胞亚群与NK细胞的影响

目的：本文探讨维甲酸抑制大鼠肝癌细胞增殖对T淋巴细胞亚群和NK细胞的影响。方法：设三个实验组,分别收集30个大鼠外周血样本,然后进行免疫荧光抗体标记。应用流式细胞仪（EPICS-XL）检测T淋巴细胞亚群和NK细胞的百分率。结果：对照组与健康组比较,CD4＋细胞数明显减少,CD8＋细胞数明显增多,CD4＋/CD8＋比值下降（P〈0.01）。维甲酸组与健康组比较,CD4＋、CD8＋和CD56＋细胞数均无显著性差异（P〉0.05）。结论：维甲酸抑制大鼠肝癌细胞增殖时对机体免疫功能的改善有一定影响。     

2型糖尿病患者T细胞亚群、TNF-α及IL-10的相关性研究

目的探讨2型糖尿病患者外周血T细胞亚群、血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10之间的相关性.方法用流式细胞仪分析46例初诊2型糖尿病(DM组)患者和39例正常对照者(NC组)的外周血T细胞亚群水平,双抗夹心酶联免疫吸附法检测血清TNF-α、IL-10的水平.同时检测空腹血糖(FPG)、空腹胰岛素(FIns)、糖化血红蛋白(GHbA1c).结果DM组CD4 、CD4 /CD8份别为(48.89±5.50)%,2.64±0.57明显高于NC组的(34.52±3.04)%、1.52±0.27,差异均有统计学意义(P＜0.05);而CD8 则明显低于NC组[(20.16±1.65)%vs(28.28±3.27)%,P＜0.05];DM组和NC组的血清TNF-o水平[(12.71±5.37)ng/L vs(8.17±2.80)ng/L],差异有统计学意义(P＜0.05);而2组血清IL-10的水平差异无统计学意义[(4.61±1.20)ng/L vs(4.36±0.84)ng/L,P＞0.05].结论机体免疫功能异常与促炎因子的启动在2型糖尿病的发生、发展中发挥着一定的作用.     

乌体林斯对合并糖尿病老年肺结核免疫的影响

目的:探讨抗结核治疗同时并用乌体林斯对合并糖尿病老年肺结核患者外周血T淋巴细胞亚群的影响。方法:对44例合并糖尿病老年肺结核患者进行抗结核治疗的同时给予乌体林斯肌肉注射,观察外周血T淋巴细胞亚群(CD3+、CD4+、CD8+、NK)的变化。结果:经乌体林斯治疗后,患者外周血CD3+、CD4+水平显著提高(P<0.01),CD4+/CD8+比值明显升高(P<0.05)。结论:乌体林斯可显著提高合并糖尿病老年肺结核患者的细胞免疫功能。     

维持性血液透析对T细胞亚群与红细胞生成素低反应性的影响

目的 通过对红细胞生成素(rHuEPO)不同反应的患者用流式细胞仪检测T细胞亚群以了解rHuEPO低反应与细胞免疫的关系及可能的作用机制.方法 将40例维持性血液透析(MHD)患者按照rHuEPO反应的不同分为第一组和第二组,rHuEPO反应低下的18例为第一组,rHuEPO反应良好的22例为第二组,另设一健康对照组20例.应用流式细胞仪检测各组患者T淋巴细胞表面CD+4、CD+8、CD+4/CD+28、CD+8/CD+28抗原的表达情况.结果 rHuEPO反应良好组和反应低下组的CD+4 T细胞、CD+8 T细胞百分比差异无统计学意义,但均显著低于对照组;rHuEPO反应低下组的CD+4 CD+28/CD+4、CD+8 CD+28/CD+8 T细胞的百分比明显低于反应良好组和对照组,而反应良好组与对照组之间无明显差异.结论 尿毒症MHD患者存在T细胞免疫表型的改变.     

成人麻疹患者T细胞亚群的变化特点

目的探讨成人麻疹患者出疹期及恢复期T细胞亚群变化特点。方法采用美国BD公司生产的Fas-calibur流式细胞仪检测麻疹患者出疹期及恢复期外周血CD3 、CD4 、CD8 T淋巴细胞,并与健康对照者进行比较。结果麻疹患者出疹期外周血CD3 、CD4 T淋巴细胞与健康对照者及恢复期比较均明显下降,差别有统计学意义(P<0.05);恢复期外周血CD3 、CD4 T淋巴细胞与健康对照者比较,差别无统计学意义(P>0.05)。结论麻疹患者出疹期细胞免疫功能显著下降,可导致机会性感染的发生,临床工作中应加强感染的防治。