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.     

Reaction product imaging: the h + d2 reaction

The differential cross section for the H + D(2) --> HD + D reaction has been measured using a technique called reaction product imaging. In this experiment, a photolytically produced beam of hydrogen (H) atoms crossed a beam of cold deuterium (D(2)) molecules. Product D atoms were ionized at the intersection of the two particle beams and accelerated toward a position-sensitive detector. The ion images appearing on the detector are two-dimensional projections of the three-dimensional velocity distribution of the D atom products. The reaction was studied at nominal center-of-mass collision energies of 0.54 and 1.29 electron volts. At the lower collision energy, the measured differential cross section for D atom production, summed over all final states of the HD(v,J) product, is in good agreement with recent quasi-classical trajectory calculations. At the higher collision energy, the agreement between the theoretical predictions and experimental results is less favorable.     

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.     

Breakdown of the Born-Oppenheimer approximation in the F+ o-D2 -> DF + D reaction

The reaction of F with H2 and its isotopomers is the paradigm for an exothermic triatomic abstraction reaction. In a crossed-beam scattering experiment, we determined relative integral and differential cross sections for reaction of the ground F(2P(3/2)) and excited F*(2P(1/2)) spin-orbit states with D2 for collision energies of 0.25 to 1.2 kilocalorie/mole. At the lowest collision energy, F* is approximately 1.6 times more reactive than F, although reaction of F* is forbidden within the Born-Oppenheimer (BO) approximation. As the collision energy increases, the BO-allowed reaction rapidly dominates. We found excellent agreement between multistate, quantum reactive scattering calculations and both the measured energy dependence of the F*/F reactivity ratio and the differential cross sections. This agreement confirms the fundamental understanding of the factors controlling electronic nonadiabaticity in abstraction reactions.     

Observation of Feshbach resonances in the F + H2 --> HF + H reaction

Reaction resonances, or transiently stabilized transition-state structures, have proven highly challenging to capture experimentally. Here, we used the highly sensitive H atom Rydberg tagging time-of-flight method to conduct a crossed molecular beam scattering study of the F + H2 --> HF + H reaction with full quantum-state resolution. Pronounced forward-scattered HF products in the v' = 2 vibrational state were clearly observed at a collision energy of 0.52 kcal/mol; this was attributed to both the ground and the first excited Feshbach resonances trapped in the peculiar HF(v' = 3)-H' vibrationally adiabatic potential, with substantial enhancement by constructive interference between the two resonances.     

Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo

In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used to induce deletion of antigen-reactive thymocytes in vivo. Mice transgenic for a T cell receptor (TCR) that reacts to this peptide contain thymocytes that progress from the immature to the mature phenotype. Intraperitoneal administration of the peptide antigen to transgenic mice results in a rapid deletion of the immature CD4+ CD8+ TCRlo thymocytes. Apoptosis of cortical thymocytes can be seen within 20 hours of treatment. These results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance.     

Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells

Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products.     

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。     

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.     

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.     

First-principles theory for the H + CH4 --> H2 + CH3 reaction

A full-dimensional quantum dynamics simulation of a hydrogen atom reacting with methane on an accurate ab initio potential energy surface is reported. Based on first-principles theory, thermal rate constants are predicted with an accuracy comparable to (or even exceeding) experimental precision. The theoretical prediction is within the range of the significantly varied experimental rate constants reported by different groups. This level of accuracy has previously been achieved only for smaller, three-or four-atom reactive systems. Comparison with classical transition state theory confirms the importance of quantum mechanical tunneling for the rate constant below 400 kelvin.     

CD4^＋T细胞表位预测及其应用

目前,运用生物软件预测CD4^＋T细胞表位的技术越来越成熟,为表位疫苗的研究提供了有利的条件。对T细胞表位预测技术及其应用进行了综述。     

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.     

Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice

The maturation of T cells in the thymus is dependent on the expression of major histocompatibility complex (MHC) molecules. By disruption of the MHC class II Ab beta gene in embryonic stem cells, mice were generated that lack cell surface expression of class II molecules. These MHC class II-deficient mice were depleted of mature CD4+ T cells and were deficient in cell-mediated immune responses. These results provide genetic evidence that class II molecules are required for the maturation and function of mature CD4+ T cells.     

米糠多糖对不同免疫状态雏鸡外周血CD4^＋和CD8^＋ T淋巴细胞亚群的影响

为探讨米糠多糖对不同免疫状态雏鸡免疫功能的调节作用机理,采用流式细胞技术检测了健康雏鸡、环磷酰胺处理雏鸡和人工感染传染性法氏囊病毒雏鸡在服用米糠多糖（剂量150 mg/（kg.d））和不服用米糠多糖情况下,外周血CD4^＋和CD8^＋T淋巴细胞亚群数量的动态变化。结果表明：米糠多糖能够提高健康雏鸡外周血CD4^＋T淋巴细胞比率,对CD8^＋T淋巴细胞作用不明显;能够提高环磷酰胺和传染性法氏囊病毒诱导免疫抑制雏鸡外周血中CD4^＋和CD8^＋T淋巴细胞数量。     

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.     

Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys

Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV)-infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and replication-defective adenoviral vectors encoding SIV proteins and then challenged them with pathogenic SIV. Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival. This survival was associated with preserved central memory CD4+ T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans.     

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.     

Conserved repetitive epitope recognized by CD4+ clones from a malaria-immunized volunteer

T cell clones obtained from a human volunteer immunized with Plasmodium falciparum sporozoites specifically recognized the native circumsporozoite (CS) antigen expressed on P. falciparum sporozoites, as well as bacteria- and yeast-derived recombinant falciparum CS proteins. The response of these CD4+ CD8- cells was species-specific, since the clones did not proliferate or secrete gamma interferon when challenged with sporozoites or recombinant CS proteins of other human, simian, or rodent malarias. The epitope recognized by the sporozoite-specific human T cell clones mapped to the 5' repeat region of the CS protein and was contained in the NANPNVDPNANP sequence.     

Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone

Nonobese diabetic (NOD) mice develop an autoimmune form of diabetes, becoming hyperglycemic after 3 months of age. This process was accelerated by injecting young NOD mice with CD4+ islet-specific T cell clones derived from NOD mice. Overt diabetes developed in 10 of 19 experimental animals by 7 weeks of age, with the remaining mice showing marked signs of the disease in progress. Control mice did not become diabetic and had no significant pancreatic infiltration. This work demonstrates that a CD4 T cell clone is sufficient to initiate the disease process in the diabetes-prone NOD mouse.