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| 1 | Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation显示文摘Regulatory T cells(Tregs)play a pivotal role in immune-tolerance,and loss of Treg function can lead to the development of autoimmunity.Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery,where they suppress self-reactive effector T cells(Teff)responses.Recently,we showed that OX40L(TNFSF4)is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation(CAP-independent)in the presence of low-dose IL-2.Therefore,we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg(tTreg)development.Development of tTregs is a two-step process:Strong T-cell receptor(TCR)signals in combination with co-signals from the TNFRSF members facilitate tTreg precursor selection,followed by a TCR-independent phase of tTreg development in which their maturation is driven by IL-2.Therefore,we investigated whether OX40 signaling could also play a critical role in the TCR-independent phase of tTreg development.OX40−/−mice had significantly reduced numbers of CD25−Foxp3low tTreg precursors and CD25+Foxp3+mature tTregs,while OX40L treatment of WT mice induced significant proliferation of these cell subsets.Relative to tTeff cells,OX40 was expressed at higher levels in both murine and human tTreg precursors and mature tTregs.In ex vivo cultures,OX40L increased tTreg maturation and induced CAP-independent proliferation of both murine and human tTregs,which was mediated through the activation of AKT-mTOR signaling.These novel findings show an evolutionarily conserved role for OX40 signaling in tTreg development and proliferation,and might enable the development of novel strategies to increase Tregs and suppress autoimmunity. | Prabhakaran Kumar Alejandra Marinelarena Divya Raghunathan Vandhana K Ragothaman Shikha Saini Palash Bhattacharya Jilao Fan Alan L Epstein Ajay V Maker Bellur S Prabhakar | 2019 | Cellular & Molecular Immunology2019，16，2： | 4 |
| 2 | 单克隆抗体TNT-1的纯化、F(ab)_2片段化及其免疫活性的测定显示文摘TNT-1是-种鼠IgG_2a单抗,已用于肿瘤病人的临床试验。本文将介绍从腹水中进一步纯化TNT-1的方法及制备其F(ah′)_2片段的条件。经Protein A亲和柱层析从小鼠腹水中提取出的lgG,再通过阳离子交换树脂柱Mono S,用缓冲液A(20 mmol/L MES,pH6.3)和缓冲液B(lmol/L NaCI),在快速蛋白液相色层(FPLC)系统上进行梯度洗脱分离,可制得纯净的TNT-1抗体,其免疫活性可达80%~85%;经纯化的TNT-1,用胃蛋白酶消化,制备F(ah′)~2片段,其消化条件是:酶的用量为抗体的1/250,pH3.8,温度37℃,时间4~5 /小时。消化后的混合物,用protein A亲和结合法除去完整的IgG,其余的F(ab′)_2和Fab、Fc等片段,在Mono S柱上,按前述的条件分离。产物TNT-1或F(ah′)_2的免疫活性,用标记抗体和过量抗原结合的方法测定;分高纯化过程中的洗脱峰,用间接免疫荧光技术监测其活性。结果戾明,TNR-1的F(ab′)_2片段的制备是成功的,色层分离纯化的方法简便而有效,并已成功地应用于批量生产。 | 刘长征 F-M Chen Alan L Epstein | 1991 | 中山医科大学学报1991，12，4： | 2 |
| 3 | Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris显示文摘 | Unger E F Goncalves L Epstein S E | 2000 | Am J Cardiol2000，85，12： | 1 |
| 4 | Nitrogen cycling in the soil-plant system along a precipitationgradient in the Kalahari sands显示文摘 | Aranibar J N Otter L Macko S A Feral C J W Epstein H E | 2004 | Global Change Biology2004，10，3： | 1 |
| 5 | Posterior fracture dislocation of the hip with fractures of the femoral head显示文摘 | Epstein HC Wiss DA Cozen L | 1985 | Clin Orthop Relat Res1985，，201： | 1 |
| 6 | Immunohisto chemical analysis of bcl-2,bax,bcl-X and mcl-1 expression in prostate cancers显示文摘 | Krajewska M Krajewski S Epstein J L | 1996 | Am J Pathol1996，148，5： | 1 |
| 7 | Characterization of cytokine-induccxl myeloid-derived suppressor cells from normal human peripheral blood mononuclem' cells 显示文摘 | Liebertz M G D J Epstein A L | 2010 | J Immuno2010，185，9： | 1 |
| 8 | Ambiguity, risk, and asset returns in continous time显示文摘 | Chen Z Epstein L G | 2002 | Econometrica2002，70，： | 1 |
| 9 | A kinetics study of the oxidation of iron ( I1 ) by nitric acid 显示文摘 | Epstein I R Kustin K Warshaw L J | 1980 | Journal of the American Chemical Socie- ty1980，102，11： | 1 |
| 10 | The McMaster Family As- sessment Device显示文摘 | Epstein N Baldwin L Bishop D | 1983 | J Marital Fam Ther1983，9，2： | 1 |
| 11 | Mixture symmetry and quadratic utility显示文摘 | CHEW S EPSTEIN L SEGAL Ustein | 1991 | Econometrica1991，59，1： | 1 |
| 12 | Use of Keratin 903 as an Adjunct in the Diagnosis of Prostate Carcinoma显示文摘 | Hedrick L Epstein JI | 1989 | Am J Surg Pathol1989，13，5： | 1 |
| 13 | Genetic engineering of herpes simplex virus and vector genomes carrying loxP sites in cells expressing Cre recombinase显示文摘 | Logvinoff C Epstein A L | 2000 | Virology2000，267，1： | 1 |
| 14 | Water on Mars: clues from deuterium/hydrogen and water contents of hydrous phases in SNC meteorites 显示文摘 | WATSON L L HUTCHEON I D EPSTEIN S | 1994 | Science1994，265，： | 1 |
| 15 | Hydrostatic Gas Journal Bearings for Micro - Turbomachinel 显示文摘 | Liu L X Teo C J Epstein A H | 2004 | Journal of Vibration and Acoustics2004，127，2： | 1 |
| 16 | ALK-1 expression in inflammatory myofibroblastie tumor of the urinary bladder显示文摘 | Tsuzuki T Magi-Galluzzi C Epstein J l | 2004 | Am J Surg Pathol2004，28，12： | 1 |
| 17 | Current concepts review:intra-artic- ular fractures of the calcaneus 显示文摘 | Epstein N Chandran S Chou L | 2012 | Foot Ankle Int2012，33，1： | 1 |
| 18 | Benefit from Bevacizumab for macular edema in central retinal vein occlusion : twelve- month results of a prospective, randomized study显示文摘 | EPSTEIN D L ALGVERE P V Von WENDT G | 2012 | Ophthalmology2012，119，： | 1 |
| 19 | Stochastic differential utility显示文摘 | EPSTEIN L G | 1992 | Econometrica1992，60，2： | 1 |
| 20 | Hydrogen and oxygen isotope ratios in nodular and bedded cherts 显示文摘 | Knauth P L Epstein S | 1976 | Geoch Cosmoch Acta1976，40，9： | 1 |
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