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51.
Lathrop SK Bloom SM Rao SM Nutsch K Lio CW Santacruz N Peterson DA Stappenbeck TS Hsieh CS 《Nature》2011,478(7368):250-254
The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T(reg)) cells. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease. Here we show that encounter with commensal microbiota results in the peripheral generation of T(reg) cells rather than pathogenic effectors. We observed that colonic T(reg) cells used T-cell antigen receptors (TCRs) different from those used by T(reg) cells in other locations, implying an important role for local antigens in shaping the colonic T(reg)-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon T(reg) TCRs. These TCRs did not facilitate thymic T(reg)-cell development, implying that many colonic T(reg) cells arise instead by means of antigen-driven peripheral T(reg)-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic T(reg) cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo T(reg)-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of T(reg) cells in response to an individual's microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota. 相似文献
52.
Summary Treatment of 3T3 cell plasma membranes with glycosidase enzymes decreased their ability to inhibit cell growth and also decreased their binding to 3T3 cells. This suggests that carbohydrate is required for complete function of inhibitory activity and that inhibition is associated with membrane adhesion. 相似文献
53.
Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein 总被引:6,自引:0,他引:6
The toxic effects of eosinophils on parasites and cells are due largely to the secretion of various granule proteins, following stimulation. In order to study this secretory process (degranulation) further, we have raised mouse monoclonal antibodies against both human eosinophil granule extracts and secretion products. From immunocytochemical studies it appears that one antibody, EG1 , recognized both the storage and secreted forms of eosinophilcationic protein (ECP), whereas antibody EG2 only bound to ECP during secretion (and extraction). This antibody also bound to eosinophil protein-X (EP-X). As both antibodies stained eosinophils in formalin-fixed tissues, they were used to demonstrate sites of eosinophil activation and secretion in chronic urticaria. The capacity of monoclonal antibodies to detect differences between storage and secreted forms of proteins is an important property of these reagents with many potential applications in cell biology. 相似文献
54.
J. D. Gupta V. J. Peterson J. D. Harley 《Cellular and molecular life sciences : CMLS》1973,29(6):664-665
Résumé Dans le cristallin et les erythrocytes de poussins à l'état embryonnaire et quelques jours après l'éclosion, l'activité de l'ATPase est beaucoup plus intense que chez d'autres animaux. Ce fait correspond bien à la forte incorporation de Rb86 dans leur cristallin.
This work was supported by grants from the National Health and Medical Research Council of Australia, the Clive and Vera Ramaciotti Foundation and the Helena Rubinstein Foundation. Inc. J. D. G. was supported by a fellowship from ATN Channel 7, Sydney. 相似文献
This work was supported by grants from the National Health and Medical Research Council of Australia, the Clive and Vera Ramaciotti Foundation and the Helena Rubinstein Foundation. Inc. J. D. G. was supported by a fellowship from ATN Channel 7, Sydney. 相似文献
55.
56.
A new class of angiotensin-converting enzyme inhibitors 总被引:22,自引:0,他引:22
A A Patchett E Harris E W Tristram M J Wyvratt M T Wu D Taub E R Peterson T J Ikeler J ten Broeke L G Payne D L Ondeyka E D Thorsett W J Greenlee N S Lohr R D Hoffsommer H Joshua W V Ruyle J W Rothrock S D Aster A L Maycock F M Robinson R Hirschmann C S Sweet E H Ulm D M Gross T C Vassil C A Stone 《Nature》1980,288(5788):280-283
Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study. 相似文献
57.
为了从带伪影的弥散加权数据中重建更准确的张量,提出了一种基于层选择的张量优化算法.首先对弥散加权图像中常见的3种伪影(波状、层间运动和对比度伪影)进行定性分析,分别提取3种对应的特征(小波标记、相似度和相关性)来识别这些伪影,从而区分出正常图层和伪影图层.然后,利用正常图层数据进行张量重建.模拟实验结果验证了这3种特征对弥散加权图像中相关伪影判断的有效性,且对波状伪影和层间运动伪影的判断率均大于90%.真实数据实验结果表明,与类似算法相比,所提算法可以更好地改善部分各向异性伪彩图中的偏色现象,在白质结构分析中提供了更准确的方向信息. 相似文献
58.
Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. 总被引:27,自引:0,他引:27
K E Nelson R A Clayton S R Gill M L Gwinn R J Dodson D H Haft E K Hickey J D Peterson W C Nelson K A Ketchum L McDonald T R Utterback J A Malek K D Linher M M Garrett A M Stewart M D Cotton M S Pratt C A Phillips D Richardson J Heidelberg G G Sutton R D Fleischmann J A Eisen O White S L Salzberg H O Smith J C Venter C M Fraser 《Nature》1999,399(6734):323-329
The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea. 相似文献
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