Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system mediated by CD4+ T cells reactive with myelin basic protein (MBP). Rats were rendered resistant to the induction of EAE by vaccination with synthetic peptides corresponding to idiotypic determinants of the beta chain VDJ region and J alpha regions of the T cell receptor (TCR) that are conserved among encephalitogenic T cells. These findings demonstrate the utility of TCR peptide vaccination for modulating the activity of autoreactive T cells and represent a general therapeutic approach for T cell-mediated pathogenesis.     

Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells

T cell vaccination against experimental autoimmune disease is herein shown to be mediated in part by anti-ergotypic T cells, T cells that recognize and respond to the state of activation of other T cells. The anti-ergotypic response thus combines with the previously shown anti-idiotypic T cell response to regulate autoimmunity.     

T cell receptor peptide therapy triggers autoregulation of experimental encephalomyelitis

Encephalitogenic T cells specific for myelin basic protein share common V beta 8 peptide sequences in their T cell receptor (TCR) that can induce autoregulatory T cells and antibodies that prevent clinical signs of experimental autoimmune encephalomyelitis (EAE). It is not known, however, if TCR peptides can treat established disease. To test its therapeutic value, TCR-V beta 8-39-59 peptide was injected into rats with clinical signs of EAE. This treatment reduced disease severity and speeded recovery, apparently by boosting anti-V beta 8 T cells and antibodies raised naturally in response to encephalitogenic V beta 8+ T cells. These results demonstrate that synthetic TCR peptides can be used therapeutically, and implicate the TCR-V beta 8-39-59 sequence as a natural idiotope involved in EAE recovery. Similarly, human TCR peptides may be effective in enhancing natural regulation of autoreactive T cells that share common V genes.     

Inhibition of experimental allergic encephalomyelitis in rats severely depleted of T cells

Lewis rats depleted of thymus-derived cells (B rats) failed to develop either experimental allergic encephalomyelitis or antibody against myelin basic protein. Lewis B rats reconstituted with 690 x 10(6) thymocytes developed experimental allergic encephalomyelitis and levels of antibody against myelin basic protein comparable to those of controls. The Lewis B rat model should be useful in the analysis of the role of thymus-derived cell populations and antibody in the induction of experimental allergic encephalomyelitis.     

Sulfatide synthesis: inhibition by experimental allergic encephalomyelitis serum

The rate of (35)S incorporation into cerebroside sulfate in cultures of embryo mouse spinal cord shows a rapid acceleration at the time of myelin formation. Exposure of cultures to dilute serum from rabbits with experimental allergic encephalomyelitis results in almost complete inhibition of sulfatide synthesis. Within 24 hours after replacement of inhibiting medium with normal medium there is an increase in sulfatide synthesis followed by myelination.     

Neonatal tolerance induced by antibody against antigen-specific receptor

Specific immunologic unresponsiveness is induced by injecting adult or neonatal mice with antibody against antigen-specific receptor (antireceptor antibody). Suppression in mice treated as adults lasts several weeks, and cells from these suppressed mice respond normally in culture. In contrast, unresponsiveness induced in neonatal mice is long-lasting; cells from these mice do not respond in culture and do not affect the response of normal cells. Evidently, antireceptor antibody reversibly blocks antigen receptors in adult animals, but induces unresponsiveness in neonatal mice by depleting the clone of receptor-bearing cells.     

T cell activation by lipopeptide antigens

Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.     

Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein.

The circumsporozoite (CS) protein has been the target for development of malaria sporozoite vaccines for a decade. However, immunization with subunit vaccines based on the CS protein has never given the complete protection found after immunization with irradiated sporozoites. BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produced antibodies and cytotoxic T cells against a 140-kilodalton protein, sporozoite surface protein 2 (SSP2). Mice immunized with P815 cells that had been transfected with either SSP2 or CS genes were partially protected, and those immunized with a mixture of SSP2 and CS transfectants were completely protected against malaria. These studies emphasize the importance of vaccine delivery systems in achieving protection and define a multi-antigen sporozoite vaccine.     

金黄色葡萄球菌诱发小鼠实验性乳腺炎研究

为建立小鼠乳腺炎模型,本试验选用35只泌乳期BALB/C雌鼠随机分成7组,其中6组于产后8~10 d分别用灭菌生理盐水和不同浓度的金黄色葡萄球菌悬液50μL经乳头管注入到小鼠的第4对(腹部)乳腺内,观察小鼠体温、组织病理学、间质宽度、腺泡壁厚度的变化以及乳腺组织中CFU、TNF-α和IFN-γ含量变化。结果表明:试验组小鼠体温呈现先下降后上升的趋势,以T3组明显;组织病理学显示乳腺上皮脱落,腺泡腔内大量炎性细胞浸润,以嗜中性粒细胞为主,腺泡内空泡减少,间隔增宽,炎症明显。而随着金黄色葡萄球菌用量的加大,乳腺组织的炎症程度加剧。T3组间质宽度高于其他组。与对照组相比,T3组小鼠乳腺组织中腺泡壁厚度、CFU、TNF-α及IFN-γ含量极显著升高(P<0.01)。结果表明金黄色葡萄球菌诱发小鼠试验性乳腺炎模型与炎症的免疫病理过程和炎性反应一致,可用作病理模型使用。     

Transfer of experimental autoimmune renal cortical tubular and interstitial disease in guinea pigs by serum

Guinea pigs injected with rabbit tubular basement membranes and Freund's adjuvant develop progressive renal cortical tubulointerstitial disease and deposit autoantibodies in their cortical tubular basement membranes. The identical, even fatal, disease may be produced in normal guinea pigs by a single intraperitoneal injection of serums obtained from guinea pigs with this tubulointerstitial disease, provided such serums contain sufficient amounts of autoantibodies against tubular basement membranes.     

BclGs对肿瘤细胞促凋亡功能的初步研究

为了探讨仅含有BH3结构域的促凋亡蛋白BclGs的促凋亡机理,从人睾丸cDNA文库中克隆BclGs基因编码区,将其与pEGFP-C1载体连接,构建载体pEGFP-BclGs,转染COS7细胞和多种肿瘤细胞(如Hela、HepG2和MCF7等),研究BclGs对肿瘤细胞的促凋亡功能。结果表明,pEGFP-BclGs可以诱导不同的肿瘤细胞凋亡,但凋亡率存在差别;BclGs在不同细胞的线粒体中均呈点状分布。线粒体是诱导肿瘤细胞凋亡的有效细胞器,BclGs在线粒体中呈点状分布。     

二氢杨梅素诱导MDA-MB-231细胞凋亡

为了探讨二氢杨梅素(dihydromyricetin,DMY)诱导人乳腺癌MDA-MB-231细胞凋亡的机制,利用倒置显微镜观察细胞形态变化,用流式细胞仪检测DMY对MDA-MB-231细胞的致凋亡能力和细胞内钙离子浓度和线粒体膜电位(ΔΨm)的改变,用蛋白质印迹(Western blotting)分析检测半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和半胱氨酸天冬氨酸蛋白酶-9(caspase-9)的变化。结果表明:MDA-MB-231细胞随DMY质量浓度加大而变圆变小,细胞存活数减少;流式细胞仪检测显示随DMY质量浓度的增加,DMY对MDA-MB-231细胞有促凋亡作用,胞内钙离子浓度逐渐增加,而线粒体跨膜电位(ΔΨm)逐渐减少;Western blotting结果显示DMY可诱导MDA-MB-231细胞中caspase-3和caspase-9蛋白质活化,并呈现浓度依赖关系。表明DMY可通过线粒体途径诱导MDA-MB-231细胞凋亡。     

T细胞表位预测及其在抗口蹄疫病毒疫苗研发中的应用研究进展

随着分子免疫学研究的不断发展,对T淋巴细胞免疫分子机制的阐释,大量T细胞表位信息以及功能基因组学资料的积累,使得基于数据驱动的预测T细胞表位的研究受到重视,可能成为疫苗研发的重要工具之一.本文阐述了T细胞表位预测的理论和方法及其在抗口蹄疫病毒疫苗研发中的应用,并讨论了未来的研究方向.     

Control of T cell function by positive and negative regulators

T cells are an essential element of the body's immune system. Engagement of the T cell receptor is responsible for initiating the signaling events that can activate, inactivate, or eliminate T cells, depending on the magnitude and duration of the signal. Control of T cell signaling occurs through both positive and negative regulation, as well as through the actions of molecular scaffolds that contribute to the formation of signaling complexes. The T Cell Signal Transduction Pathway at the STKE Connections Maps highlights the molecular components that are responsible for T cell activation. Understanding the mechanisms that regulate T cell responsiveness will aid in the development of therapeutic agents to treat infection, cancer, and autoimmune disease and immune deficiency.     

苯丙噻重氮(BTH)诱导黄瓜幼苗抗黑星病的研究

通过 ０．１２５～２ μｇ／ｍＬ ＢＴＨ对黑星菌孢子萌发率及菌丝生长速率影响的测试，证明 ＢＴＨ对黑星菌孢子萌发及菌丝生长均无直接抑制作用，采用 ０．１２５～２ ｆｉｇ／ｍＬ ＢＴＨ喷洒黄瓜幼苗后均可诱导黄瓜对黑星病产生一定程度的抗性，其中 ＩＰｇ／ｍＬ ＢＴＨ处理长春密刺、津研７号、津春３号后，平均诱导效果分别为 ９１．１７％、８０．９４％、９７．０７％。１μｇ／ｍＬ　ＢＴＨ诱导黄瓜幼苗抗黑星病的效果显著高于 ０．１％水杨酸、０．１％苯酚、０．１％氯化钾。ＢＴＨ处理后，对长春密刺的平均诱导效果可达８３．９０％，而水杨酸、苯酚、氯化钾对其诱导效果分别为１７．１７％、３２．４２％、３３．２４％。     

茄类镰刀菌引起的橡胶树茎杆溃疡病防治药剂筛选试验

通过菌落生长速率法对由茄类镰刀菌(Fusarium solani)引起的橡胶树茎杆溃疡病进行防控药剂筛选试验。结果表明,卉友(50%咯菌腈WP)的EC_(50)最小,抑菌效果最好,其次是施保功(50%咪鲜胺锰盐WP)和多菌灵(50%多菌灵WP),凯润(250g/m L吡唑醚菌酯EC)和甲基硫菌灵(70%甲基托布津WP)的EC_(50)最大,抑制作用最差。3个混配组合中多菌灵和施保功混配具有增效作用,其他组合表现加和作用。建议生产上使用咯菌腈、咪鲜胺锰盐和多菌灵等防治橡胶树茎杆溃疡病。     

Programmed cell death of T cells signaled by the T cell receptor and the alpha 3 domain of class I MHC

As well as being activated or rendered unresponsive, mature T lymphocytes can be deleted, depending on the signals received by the cell. Deletion by programmed cell death (apoptosis) is triggered if a T cell that has received a signal through its T cell receptor complex also receives a signal through the alpha 3 domain of its class I major histocompatibility complex (MHC) molecule. Such a signal can be delivered by a CD8 molecule, which recognizes the alpha 3 domain, or by an antibody to this domain. Precursors of both cytotoxic T lymphocytes (CTL's) and T helper cells are sensitive to this signal but become resistant at some point before completing differentiation into functioning CTL's or T helper cells. Because CTL's carry CD8, they can induce cell death in T cells that recognize them. This pathway may be important in both removal of autoreactive T cells and immunoregulation.