轮状病毒肠炎患儿外周血CD4+CD29+T细胞表达及其与治疗关系

目的 了解轮状病毒(RV)肠炎患儿外周血CD4+CD29+T细胞表达及其与治疗关系.方法 69例RV肠炎患儿分为观察组及对照组,分别给予抗RV免疫球蛋白及常规抗病毒治疗;比较两组患儿治疗前后外周血CD4+CD29+T细胞、IL-2、IL-12水平变化,粪便内RV-RNA含量及腹泻天数差异.结果 观察组治疗后CD4+CD29+T细胞、IL-2及粪便内RV-RNA水平均显著低于治疗前及对照组(P＜0.01),而IL-12水平显著增高(P＜0.01).观察组腹泻天数明显少于对照组(P＜0.01).RV肠炎患儿粪便内RV-RNA、腹泻天数与外周血CD4+CD29+T细胞、IL-2水平呈正相关(P＜0.01或0.05),而与IL-12呈负相关(P＜0.05).结论 外周血CD4+CD29+T细胞、IL-2水平升高及IL-12水平降低是RV肠炎的细胞免疫特征,且与病毒数量及腹泻程度明显相关.     

子宫内膜异位症不孕患者手术前后CD4+CD29+T细胞变化与妊娠率的关系

目的 了解子宫内膜异位症(endometriosis,EMS)不孕患者手术前后CD4+CD29+T细胞变化及其与妊娠率的关系.方法 收集具有手术指征的EMS致不孕患者36例(手术组),无手术指征EMS患者38例(非手术组),同时选取38例健康女性作对照(健康组).观察EMS患者治疗前后外周血CD4+CD29+T细胞及其细胞因子白介素1(IL-1)、白介素4(IL-4)及CA125水平的变化,并将其与妊娠率进行相关性分析.结果 EMS不孕患者CD4+CD29+T细胞、IL-1、IL-4及CA125水平均显著高于健康女性(P＜0.01).治疗后,手术组和非手术组的CD4+CD29+T细胞、IL-1及CA125水平均显著低于治疗前,且手术组明显低于非手术组(P＜0.01);手术组的妊娠率明显高于非手术组(P＜0.05).CD4+CD29+T细胞、IL-1及IL-4与CA125均呈显著正相关,而与妊娠率呈显著负相关(P＜0.05或0.01).结论 CD4+CD29+T细胞升高是EMS不孕患者的重要免疫学表现,手术可显著降低该细胞及其细胞因子水平,提高妊娠率.     

北京市空气污染物对过敏性鼻炎的影响研究

 以2009年3月19日至2010年3月18日间北京医院耳鼻喉—头颈外科的过敏性鼻炎（AR）门诊就诊病人观测为基础,结合北京市空气质量,探讨空气质量与AR的关系。结果表明, AR患者的人数均随年龄的增长呈现先增加后减少的趋势,以中青年龄段（21～50岁）人数最多。春、秋季是过敏性鼻炎的易发时期,夏、冬季发病率相对较低。AR日就诊人数的时间变化趋势与空气中PM10,SO2,NO2的浓度变化具有一定的时间对应性,在观测的上半期内尤为明显,表明在短期内空气中PM10,SO2,NO2浓度的增加会直接影响AR的发生与症状加重,并导致就诊人数增加     

TLR7配体Loxoribine对调节性T细胞抑制作用的解除

调节性T细胞是机体免疫功能的重要调节因素,近年来的研究提示Toll样受体可以直接或间接的调控调节性T细胞的抑制功能。作者的研究显示:在CD4、Treg和DC反应体系中加入TLR7配体Loxoribine后CD4 T细胞的增殖增强,Treg的抑制功能丧失;进一步用Loxoribine分别处理CD4 T细胞、Treg、和DC细胞后发现,Loxoribine处理的DC,一方面使CD4 T细胞增殖增强,一方面使Treg抑制功能丧失;且通过trans-well试验证明Loxoribine作用于DC使Treg抑制功能丧失是通过DC释放的可溶性分子介导的,而不是通过细胞与细胞之间的接触来实现的。     

CD4+CD25+Foxp3+调节性T细胞在血液系统疾病中的研究进展

CD4＋CD25＋Foxp3＋调节性T细胞（CD4＋CD25＋Foxp3＋regulatory Tcell,Tregs）是能抑制自身免疫T细胞活化的T细胞亚群,具有免疫无能和免疫抑制两大特征。Tregs的数量和功能在移植排斥反应、多种自身免疫性疾病的发生及肿瘤免疫逃逸中发挥着重要作用,它与血液系统疾病的发生发展密切相关,对预后判断及指导治疗具有一定的意义。本文就Tregs的来源、功能及其与血液系统疾病的关系作一综述。     

SLE患者CD4+CD25+调节性T细胞及Foxp3基因表达的研究

目的:研究系统性红斑狼疮(SLE)患者外周血CD 4 CD 25 调节性T细胞及Foxp3基因的表达水平,了解它们在SLE发病机制中的作用。方法:分别收集25例SLE患者(SLE组)及健康人(对照组)外周抗凝静脉血,分离纯化T淋巴细胞。PE标记抗CD 4单抗,F ITC标记的抗CD 25单抗,作双色流式细胞术,分析SLE患者外周血CD 4 CD 25 调节性T细胞百分率,RT-PCR检测T细胞Foxp3 mRNA表达。结果:SLE组外周血CD 4 T、CD 4 CD 25 T细胞百分率及T细胞Foxp3 mRNA水平均低于对照组(P<0.01),并且CD 4 CD 25 T细胞百分率与Foxp3mRNA水平呈依赖关系(P<0.01)。结论:SLE患者外周血存在细胞免疫功能失调,CD 4 CD 25 调节性T细胞数量减少和Foxp3mRNA表达下调可能与SLE的免疫学发病机制有关。     

CD4~+CD25~+调节性T细胞的研究进展

异基因造血干细胞移植技术是血液系统恶性肿瘤治疗上的一个历史性突破,但移植排斥反应及移植物抗宿主病(graft versus host disease,GVHD)极大地限制该技术应用,而CD4+CD25+调节性T细胞(regulatory Tcells,Tregs)的发现有可能解决该难题。Tregs是一类具有免疫调节功能的T淋巴细胞,通过细胞接触和分泌抑制性细胞因子等途径,在维持机体免疫自稳、调控免疫应答方面起重要作用。有动物实验表明Tregs能够预防移植排斥和GVHD的发生,同时保留移植物抗白血病作用的功能。该文综述了其特性、作用机制以及在移植免疫耐受中的作用和应用前景。     

抗原浓度和DC数量对OT-I小鼠CD8+ T细胞分化与增殖的影响

【目的】探讨细胞毒性T细胞(CTL)表位肽SIINFEKL浓度和树突状细胞(DC)数量对CD8+T细胞活化和增殖的影响。【方法】用小鼠重组粒细胞集落刺激性生物因子(GM-CSF)和IL-4诱导骨髓细胞来源的DC增殖和分化,将所得成熟树突状细胞(maDC)和SIINFEKL抗原肽,与免疫磁珠法分离的OT-I小鼠CD8+T细胞共培养。用不同质量浓度的SIINFEKL(100,10,1,0.1,0.01和0.001 ng/mL)或不同数量的DC(DC/T比例分别为1/20和1/5)与CD8+T细胞共培养,刺激CD8+T细胞增殖分化。于共培养不同时间收集细胞,流式细胞术测定CD8+T细胞的数量、分裂速度、细胞表面活化分子的表达丰度,碘化丙叮(PI)染色测定细胞活力。【结果】在任一DC/T比例下,SIINFEKL浓度过低,均不能引起CD8+T细胞的充分增殖,而高于CD8+T细胞最佳增殖浓度的SIINFEKL则导致CD8+T细胞数量减少;在SIINFEKL质量浓度为0.001~0.1 ng/mL时,增加DC数量能促进CD8+T细胞的扩增;而SIINFEKL质量浓度为1~100 ng/mL时,提高DC数量反而导致CD8+T细胞数量减少;高浓度抗原和DC数量能有效诱导CD8+T细胞的活化和分裂增殖,但过量刺激会使细胞死亡,导致CD8+T细胞数量减少。【结论】CD8+T细胞的增殖受DC数量和抗原肽浓度的共同调节,要获得持久有效的CD8+T细胞免疫,必须保证CD8+T细胞得到足够的抗原信号,同时避免抗原信号过强导致的细胞活化后死亡。     

人外周血CD4+ T细胞F-actin的超分辨SIM成像

通过合成lifeact序列,将其克隆到pEGFP-C1载体上,构建了pEGFP-C1-Lifeact质粒,转染原代CD4+T细胞,实现对CD4+T细胞F-actin的荧光标记,结合超分辨3D-SIM荧光成像技术,研究人外周血CD4+T细胞F-actin的精细结构,并对其动力学过程进行连续观察。结果表明,CD4+T细胞F-actin分布在细胞膜周围,处于解聚和聚合的动态平衡状态,与普通荧光显微镜相比,超分辩SIM成像F-actin结构更加清晰,分辨率提高2~4倍。     

重组鸡α-干扰素对鸡外周血T淋巴细胞亚类的影响

重组鸡α-干扰素(rChIFN-α)静脉注射4~6周龄SPF鸡,24 h后采血分离淋巴细胞,通过流式细胞术测定不同时间外周血中CD4+和CD8+T淋巴细胞的百分率。结果显示,rChIFN-α可以在48~72 h内明显提高CD4+T淋巴细胞的百分率,并下调CD8+T淋巴细胞的百分率,证明rChIFN-α具有显著的免疫调节作用。     

A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory

The delivery of CD4 help to CD8+ T cell responses requires interactions between CD40 and CD40 ligand and is thought to occur through antigen-presenting cell (APC) activation. Here we show that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs. Activated CD4+ and CD8+ T cells expressed CD40; and in the absence of this protein, CD8+ T cells were unable to differentiate into memory cells or receive CD4 help. These results suggest that, like B cells, CD8+ T cells receive CD4 help directly through CD40 and that this interaction is fundamental for CD8+ T cell memory generation.     

Demethylated CD8 gene in CD4+ T cells suggests that CD4+ cells develop from CD8+ precursors

Mature T cells and medullary thymocytes bear either the CD4 or CD8 differentiation antigen. Precursor cells in the thymus express neither CD4 nor CD8 (CD4-8-), but most cortical thymocytes are CD4+8+. Whether CD4+ and CD8+ mature T cells arise directly from CD4-8- precursors or from a CD4+8+ intermediate remains unresolved. In this study, methylation of the CD8 gene in murine T cells and thymocytes was examined. There was progressive demethylation of the CD8 gene in the thymus during the transition from CD4-8- to CD4+8+. A similar pattern of demethylation of the CD8 gene was seen in CD4+ mature T cells, suggesting previous expression of CD8 in the CD4+ lineage.     

Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4

Most immature CD4+CD8+ thymocytes express only a small number of T cell receptor (TCR) molecules on their surface, and the TCR molecules they do express are only marginally capable of transducing intracellular signals. TCR expression and function was not intrinsically low in immature CD4+CD8+ thymocytes, but was found to be actively inhibited by CD4-mediated signals. Indeed, release of CD4+CD8+ thymocytes from CD4-mediated signals resulted in significant increases in both TCR expression and signaling function. These results suggest that, in CD4+CD8+ cells developing in the thymus, increased TCR expression and function requires release from CD4-mediated inhibition.     

Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function

CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases.     

Control of homeostasis of CD8+ memory T cells by opposing cytokines

Memory T cells maintain their numbers for long periods after antigen exposure. Here we show that CD8+ T cells of memory phenotype divide slowly in animals. This division requires interleukin-15 and is markedly increased by inhibition of interleukin-2 (IL-2). Therefore, the numbers of CD8+ memory T cells in animals are controlled by a balance between IL-15 and IL-2.     

AA肉鸡生长过程中血液CD3+、CD4+和CD8+T淋巴细胞亚群的变化规律

为了进一步了解AA肉鸡血液T淋巴细胞及其CD4 、CD8 亚群所占比例的变化规律及对免疫系统中的重要作用,使用流式细胞仪对1、3、5、7、14、21、28、35、42、的日龄AA肉鸡血液CD3 T淋巴细胞和CD4 、CD8 T细胞亚群比例进行检测.结果表明,1～5日龄CD3 T淋巴细胞含量逐渐升高,7日龄突然下降,14～21日龄急速升高,并达到最高峰后急速下降至28日龄,35～49日龄时相对趋于平稳状态;CD4 T细胞含量1～3日龄明显低于其余日龄,3～5日龄急速上升,7～14日龄增加缓慢,21日龄时达到最高峰后急速下降至28日龄,35～49日龄时基本趋于平稳状态;CD8 T细胞含量1～5日龄缓慢上升,5～7日龄急速下降后,再急速上升到14日龄,14～28日龄再下降,此后直至49日龄均在此水平上处于平稳状态.CD4 /CD8 比例:1～7日龄缓慢增加,7～14日龄比例急速下降至最低,14～21日龄时比例增加到最高峰后急速下降至28日龄,但比例数值高于前1～7日龄,28～49日龄比例趋于平稳状态.表明AA雏鸡在1～7日龄时其免疫功能逐渐提高,14日龄时细胞免疫功能明显减弱,这可能与CD8 T淋巴细胞含量高有关,21日龄时机体细胞免疫水平达最高状态,在28日龄后肉鸡细胞免疫功能基本保持稳定状态,但仍需要加强饲养管理.     

CD8+ T cell cross-priming via transfer of proteasome substrates

"Cross-priming" describes the activation of na?ve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.     

Regulation of CD8+ T cell development by thymus-specific proteasomes

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.