简介:Inthepresentstudy,theeffectofelectroacupuncture(EA)onimmunesystemwasobservedintheratbyusingmicro-wholeblooddirectimmunofluoreseenceStainingassaytodetectchangesoftheperipheralbloodTlymphocytesubgroupandemployingredbloodcell(RBC)C3breceptor-yeastrosettetestandredbloodcell-ICrosettetesttoanalyzeerythroeyticimmunefunction.ResultsshowedthatafterEAof“Zusanli”(ST36),CD4^+,RBC-C3bRRandRBC-ICRintheperipheralbloodofthenormalratsincreasedsignificantlywhileCD8^+hadnoanyconsiderablechangesandapositivecorrelationbetweenCD4+andRBC-C3bRRwasfound.Inimmuoosuppressionmodelrats,thevaluesofCD4^+andRBC-C3bRRwereobviouslylowerthanthoseofthenormalcontrolgroupwhileCD8^+hadnoanystrikingchanges;butafterEAtreatment,therewerenoevidentdifferencesbetweenEAgroupandnormalcontrolgroupintheabove-mentionedindexes.Therewerealsonoanysignificantdifferencesbetweennon-acupointgroupandnormalcontrolgroupinthoseindexes.ResultssuggestthatEAof“Zusanli”(ST36)canraiseTcellimmunefunctionandRBCadhesionfunctioninbothnormalratsandimmunosuppressionmodelrats,bothofwhichpresentapositivecorrelation.
简介:WehavedevelopedandtestedchimericT-cellreceptors(TCR)specificforp185HER2.Intheseexperiments,retroviralvectorsexpressingtheN297orN29ξreceptorswereconstructedinpRET6.AmphotropicviralproducercellswereestablishedintheGALV-basedPG13packagingcellline.Ficollpurifiedhumanperipheralbloodlymphocytes(PBL)werevitallytransducedusinganoptimizedprotocolincorporatingactivationwithimmobilizedanti-CD3/anti-CD28monoclonalantibodies,followedbyviralinfectioninthepresenceoffibronectinfragmentCH296.Transducedcellswereco-culturedwithhumantumorcelllinesthatoverexpress(SK-OV-3)orunderexpress(MCF7)p185HER2toassayforantigenspecificimmuneresponses.BothCD4^+andCD8^+T-cellstransducedwiththeN297orN29ξchTCRdemonstratedHER2-specificantigenresponses,asdeterminedbyreleaseofTh1likecytokines,andcellularcytotoxicityassays.OurresultssupportthefeasibilityofadoptiveimmunothempywithgeneticallymodifiedT-cellsexpressingachTCRspecificforp185HER2.
简介:AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.
简介:AbstractObjective:To analyze the proportion of peripheral regulatory T cells (Tregs) and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain (TIGIT) and CD226 on Tregs in patients with recurrent spontaneous abortion (RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+ Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group (4.41 % ± 1.54%) was significantly lower than that in the control group (5.27% ± 1.52%, P = 0.0374). Compared with the normal pregnant women, patients with RSA showed decreased TIGIT expression (54.75 ± 9.70% vs. 63.07 ± 12.48%, P = 0.0066) and increased CD226 expression on Tregs (25.59% ± 8.22% vs. 20.46% ± 6.97%, P = 0.0168). The ratio of CD226 to TIGIT in the RSA group (0.48 ± 0.19) was higher than that in the control group (0.34 ± 0.15, P = 0.0027). The proportion of TIGIT+CD226+ Tregs was significantly lower in patients with RSA (9.30% ± 4.95% vs. 13.43% ± 4.72%, P = 0.0020) than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.
简介:Wehaveconfirmedefficientanti-tumoractivitiesoftheperipherallymphocytestransducedwithap185HER2-specificchimericT-cellreceptorgenebothinmurineandinhumaninourpreviousstudies.TofurthertestthefeasibilityofchimericT-cellreceptorinabonemarrowtransplantationmodel,wefirst,madetwomurinetumorcelllines:MT901andMCA-205,toexpresshumanp185HER2byretroviralgenetransduction.MurinebonemarrowcellswereretrovirallytransducedtoexpressthechimericT-cellreceptorandgene-modifiedbonemarrowcellsweretransplantedintolethallyirradiatedmouse.Sixmonthsposttransplantation,p185HER2-positivetumorcells:MT-901/HER2orMCA-205/HER2wassubcutaneouslyorintravenouslyinjectedtomakemousemodelssimulatingprimarybreastcancerorpulmonarymetastasis.Theinvivoanti-tumoreffectsweremonitoredbythesizeofthesubcutaneoustumororcountingthetumornodulesinthelungsafterIndiainkstaining.ThesizeofthesubcutaneoustumorwassignificantlyinhibitedandthenumberofpulmonarynodulesweresignificantlydecreasedinmouserecipientstransplantedwithchimericT-cellreceptormodifiedbonemarrowcellscomparedwiththecontrolgroup.Ourresultssuggesttheefficientinvivoanti-tumoractivitiesofchimericT-cellreceptorgenemodifiedbonemarrowcells.
简介:AbstractCD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy is effective in refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL). This review focuses on achievements, current obstacles, and future directions in CAR-T research. A high complete remission rate of 68% to 93% could be achieved after anti-CD19 CAR-T treatment for B-ALL. Cytokine release syndrome and CAR-T-related neurotoxicity could be managed. In view of difficulties collecting autologous lymphocytes, universal CAR-T is a direction to explore. Regarding the high relapse rate after anti-CD19 CAR-T therapy, the main solutions have been developing new targets including CD22 CAR-T, or CD19/CD22 dual CAR-T. Additionally, some studies showed that bridging into transplant post-CAR-T could improve leukemia-free survival. Some patients who did not respond to CAR-T therapy were found to have an abnormal conformation of the CD19 exon or trogocytosis. Anti-CD19 CAR-T therapy for R/R B-ALL is effective. From individual to universal CAR-T, from one target to multi-targets, CAR-T-cell has a chance to be off the shelf in the future.
简介:类脂化合物椽子的第一外观,或类脂化合物像木排的结构,被cryo电子的显微镜学偶尔作为洞在1980年代观察,例如caveolae。然而,充分类脂化合物木排理解被T房间激活,病毒entry/budding,和另外的膜事件的研究归因。在T房间和抗原介绍房间的相互作用期间,在胆固醇和sphingolipids被充实的地方,高度组织的结构在二个房间的接口被形成,并且形成液体断断续续地便于发信号的蛋白质的订的阶段。类脂化合物椽子也涉及病毒入口和汇编。在这评论,我们将讨论cholesterol-sphingolipid漂浮microdomain,是的类脂化合物木排血浆膜的唯一的分隔空间与保证蛋白质和类脂化合物的正确细胞内部的交通的生物功能,例如由在这些microdomains集中某些蛋白质的蛋白质蛋白质相互作用,当排除其它时。我们也讨论类脂化合物椽子的混乱与不同疾病有关,老化,和我们特别为抗病毒和反发炎作为药品的目标利用类脂化合物椽子,特别地由类脂化合物椽子的抑制或混乱为爱滋病预防和保护控制HIV感染的一条新途径。
简介:T房间受体贝它链的侧面变量(TRBV)基因通常与病毒感染或癌症在题目扭曲。融化的基因光谱模式(GMSP)能被用来决定TRBV基因家庭的侧面。从从尖锐肝炎B病毒感染(AHI)恢复了的题目在外部血淋巴细胞探索TRBV家庭的肖像,外部血mononuclear房间(PBMC)被分开并且进一步排序+和CD8+T房间子集进CD4。TRBV的分子的特征补足的决定区域3(CDR3)主题用GMSP分析被决定。当GMSP侧面显示出一座单个山峰时,monoclonally扩展的TRBV基因被克隆并且定序。多重TRBV基因的扭曲的扩大在CD4+和CD8+T房间子集和PBMC之中被观察。在CD8+T房间子集的monoclonally扩展的TRBV基因的频率比CD4+T房间子集和PBMC的显著地高。比作TRBV基因家庭,TRBV11,BV15和BV20的另外的成员主要在恢复AHI题目在外部血淋巴细胞的全部剧目被表示。TRBV5.1和BV20CDR3的相对保存的氨基酸主题也在CD4+和CD8+T房间子集被检测。这些结果在恢复AHI题目表明多重偏导的TRBV家庭的存在。特别从CD8+T房间子集,TRBV11,BV15和BV20可能与有AHI的题目的致病相关。有相对保存的CDR3主题的优先地选择的TRBV5.1和BV20可以是为长期的HBV感染的个性化的处理的潜在的目标。
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简介:AbstractLike antibody evaluation, using an effective antigen-specific T-cell immunity assessment method in coronavirus disease 2019 (COVID-19) patients, survivors and vaccinees is crucial for understanding the immune persistence, prognosis assessment, and vaccine development for COVID-19. This study evaluated an empirically adjusted enzyme-linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity in 175 peripheral blood samples from COVID-19 convalescents and healthy individuals. Results of viral nucleic acid were used as the gold standard of infection confirmation. The SARS-CoV-2M peptide pool had higher sensitivity of 85% and specificity of 71% for the single peptide pool. For combined peptide pools, the parallel evaluation (at least one of the peptide pools is positive) of total peptide pools (S1&S2&M&N) had higher sensitivity (up to 93%), and the serial evaluation (all peptide pools are positive) of total peptide pools had higher specificity (up to 100%). The result of the serial evaluation was better than that of the parallel evaluation as a whole. The detection efficiency of M and N peptide pool serial evaluation appeared the highest, with a sensitivity of 80% and specificity of 93%. This T-cell immunity detection assay introduced in this report can achieve high operability and applicability. Therefore, it can be an effective SARS-CoV-2-specific cellular immune function evaluation method.
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简介:AbstractBackground:There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P= 0.001), chemotherapy-resistant disease (41% vs. 8%, P= 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
简介:与一级的CD8约会主要组织亲和性抗原极大地提高T房间激活,但是这怎么被完成,不是清楚的。我们探讨CD8的调停抗体的结扎是否独自导致在T房间克隆改变的transcriptional的问题,用基因表示的连续分析。尽管它没能导致公开phenotypic变化,我们发现CD8结扎深刻地在T房间克隆改变抄写,在比得上由CD3的调停抗体的结扎导致了那的规模。然而,产生变化的特性与是实质地禁止的CD8结扎的网效果是不同的。我们推测那绑扎的CD8导致弱,T房间受体(TCR)调停了TCR对手的效果暗示的禁止的信号。我们的结果暗示CD8结扎独自不能因为它没能充分导致NFAT依赖的抄写,激活T房间克隆。
简介:Granulocyte巨噬细胞刺激殖民地的因素(GM-CSF)是一个重要造血的生长因素和有免疫力的调节的人。GM-CSF也在各种各样的传播白血球的功能的活动有深刻效果。它被许多房间类型在收到有免疫力的刺激之上包括T房间,巨噬细胞,endothelial房间和成纤维细胞生产。尽管GM-CSF局部地被生产,它能以一种paracrine方式行动到在主人防卫提高他们的功能的成员传播neutrophils,单核白血球和淋巴细胞。最近的集中的调查为它增加树枝状的房间(DC)成熟和功能以及巨噬细胞活动的能力作为一个有免疫力的助手在GM-CSF的应用程序上被集中。在经历化疗的癌症病人对待嗜中性白血球减少症临床上被使用,在在治疗期间的爱滋病病人,并且在在骨髓移植以后的病人。有趣地,GM-CSF-deficient老鼠的造血的系统看起来正常;最重要的变化在一些特定的T房间回答。尽管GM-CSF的分子的克隆用T房间的cDNA图书馆被执行,T房间在激活以后生产GM-CSF,是众所周知的,在T房间功能上有在由T房间和它的效果的生产的这cytokine的系统的调查的缺乏。在这篇文章,我们将在T房间主要集中于GM-CSF的免疫生物学。
简介:免疫疗法和化疗的联合为癌症的某些类型的治疗被认为是一条有希望的途径。然而,内在的机制需要充分被调查为癌症chemoimmunotherapy指导更有效的协议的设计。联系危险的分子的模式(阻尼)能激活有免疫力的房间,是众所周知的,包括树枝状的房间(DC),经由像使用费的受体(TLR);然而,在有免疫力的反应的激活免除化学对待药的肿瘤房间的阻尼的角色需要进一步被阐明。这里,我们发现那colorectal与oxaliplatin(OXA)对待的癌症(CRC)房间或5氟尿嘧啶(5-Fu)释放了高活动性的组盒子1的高水平(HMGB1)和热吃惊蛋白质70(HSP70)。在OXA/5-Fu治疗以后,也展出的CRC病人的sera增加了HMGB1和HSP70的层次,哪个是著名阻尼。与OXA/5-Fu对待的垂死的CRC房间的上层清液支持了老鼠和人的DC成熟,与HLA医生,CD80和CD86表示和IL-1β的改进的upregulation;,TNF-α;,MIP-1α;,MIP-1β;,RANTES和IP-10生产。由DC组成的疫苗与导致的化学上强调的CRC房间的上层清液搏动了更重要的IFN-γ;在vitro并且在vivo生产Th1反应。然而,化学上强调的CRC房间的上层清液没能在TLR4缺乏的DC导致phenotypic成熟和cytokine生产,显示在导致阻尼的DC成熟和激活的TLR4的一个必要角色。而且,有化学上强调的CRC房间的上层清液的pulsing高效地没导致IFN-γ;在TLR4缺乏的DC生产Th1反应。一起,这些结果证明免除化学上强调的癌症房间的阻尼能经由TLR4激活DC并且提高反肿瘤T房间有免疫力的回答的正式就职,描出一条临床上相关的免疫助手小径由阻尼被触发。
简介:客观:为了改进倔强的脸中部的外部T房间non-Hodgkin鈥檚的功效,有L天门冬氨酰胺酶(LASP)的淋巴瘤(MPTC-NHL)基于抢救化疗。方法:有倔强的MPTC-NHL的21个病人被分析,11patients(LASP组)收到了L天门冬氨酰胺酶基于的抢救化疗由L天门冬氨酰胺酶,长春新碱和dexame-thosone组成。没有L天门冬氨酰胺酶,10个病人(控制组)收到了抢救联合化疗。结果:完全的宽恕率为LASP组是45.6%,0.0%为控制组织(P<0.05)。全面反应率(CR+PR)为LASP组是63.6%,10.0%为控制组织,分别地(P<0.05)。2年的幸存率为LASP组是45.5%,0.0%为控制组织(P<0.05)。LASP的主要不利效果是白细胞减少,浆液bilirubin和多糖症的举起。结论:LASP基于的初步的临床的学习表演抢救化疗可以与倔强的MPTC-NHL改进反应率和病人的2年的幸存率。进一步继续学习是必要的。