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Abstracts from the 12th Congress of the International Society for Organ Donation and Procurement November 21–24, 2013 / Sydney, Australia 第12届国际器官捐赠与获取学会大会摘要2013年11月21日至24日/澳大利亚悉尼
Pub Date : 2013-11-27 DOI: 10.1097/01.tp.0000438970.80290.d5
M. Wicclair
s from the 12th Congress of the International Society for Organ Donation and Procurement November 21–24, 2013 / Sydney, Australia
2013年11月21日至24日,澳大利亚悉尼,国际器官捐赠与获取学会第12届大会
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引用次数: 1
IPITA 2013 Abstracts Supplement IPITA 2013摘要补编
Pub Date : 2013-09-27 DOI: 10.1097/tp.0b013e3182a7ab68
M. Vantyghem, D. Quintin, W. Karrouz, J. Hurtevent, V. Raverdy, R. Caiazzo, C. Noel, J. Kerr-Conte, F. Pattou, Shari Messinger-Cayetano, K. Rouskas, R. Alejandro, M. Rickels, F. Barton
Objective: Long-term benefit-risk ratio of islet transplantation rem unclear. We explored the evolution of peripheral and autonomic ne pathy during 5 years after islet transplantation with the Edmonton pr col in type 1 diabetic patients. Patients and Methods: Twenty-one patients (13 islet-alone 8 islet-after-kidney) were enrolled in this prospective cohort study. transplantation consisted of 2 or 3 sequential infusions with IL2r sirolimus tacrolimus immunosuppression. All patients underwent logical evaluation, continuous blood pressure and continuous gluc monitoring (CGM), lower-limb electrophysiological testing and car vascular autonomic testing (R-R variation with paced breathing, Vals ratio, postural heart rate and blood pressure changes) before transp tation and yearly during 5 years. Outcomes were analyzed in inten to treat. Results: At 5 years, islet remained functional in 18 patients (85 Ten patients (48%) were insulin-independent with a median (I HbA1c at 6.0 (5.8–6.7) % vs. 7.8 (6.9-8.3) % in those requiring ins (p<0.001). The medians of sensory action potential (p<0.05) and sensory and motor nerve conduction velocities (p<0.01) improved tween 0 and 5 years. All 4 parameters significantly correlated negati with mean glucose / CGM and all outcomes except sensory nerve duction velocity correlated negatively with triglycerides (p≤0.01). S sory conduction velocity correlated negatively with glucose variab (SD) / CGM (p<0.01). Tacrolimus levels negatively correlated with m conduction parameters (p≤0.02). All four parameters correlated p tively with ß score or post-prandial C-peptide level (p<0.05). Cardio cular reflex testing did not change over the 5–year follow-up. Conclusion: islet-alone or after-kidney transplantation improved nificantly sensory nerve conduction parameters but not autonomic n ropathy after 5 years. Mean glucose was the main factor associated this improvement. (ClinicalTrial.gov: NCT00446264 / NCT01123187).
目的:胰岛移植的远期获益-风险比尚不清楚。我们探讨了1型糖尿病患者在埃德蒙顿胰岛移植后5年内周围神经和自主神经病变的演变。患者和方法:21例患者(13例单独胰岛治疗8例肾后胰岛治疗)被纳入这项前瞻性队列研究。移植包括2或3次连续输注IL2r西罗莫司他克莫司免疫抑制剂。所有患者在转运前及转运5年期间每年接受逻辑评估、连续血压和连续血糖监测(CGM)、下肢电生理测试和血管自主神经测试(R-R随呼吸节奏变化、Vals比、体位心率和血压变化)。结果分析的意向治疗。结果:5年时,18例患者(85例)胰岛保持功能,10例患者(48%)为胰岛素独立型,中位(I) HbA1c为6.0(5.8-6.7)%,而需要胰岛素的患者为7.8 (6.9-8.3)% (p<0.001)。感觉动作电位中位数(p<0.05)、感觉和运动神经传导速度中位数(p<0.01)在0 ~ 5岁间显著提高。4项指标均与平均葡萄糖/ CGM呈显著负相关,除感觉神经传导速度外,其余指标均与甘油三酯呈显著负相关(p≤0.01)。感觉传导速度与葡萄糖变量(SD) / CGM呈负相关(p<0.01)。他克莫司水平与m传导参数呈负相关(p≤0.02)。4项指标均与ß评分或餐后c肽水平呈正相关(p<0.05)。在5年的随访中,心血管反射测试没有变化。结论:胰岛单独或肾移植后5年感觉神经传导参数明显改善,但自主神经病变无明显改善。平均血糖是与这种改善相关的主要因素。(ClinicalTrial.gov: NCT00446264 / NCT01123187)。
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引用次数: 1
Research Highlights and Editors’ Picks 研究亮点和编辑精选
Pub Date : 2013-01-27 DOI: 10.1097/01.tp.0000431075.93885.89
Kumar Kuna, Chougule, MJ Elliott, De Coppi, Speggiorin, JJ Hsuan, Lowdell, Mw, Birchall
Recent years have witnessed remarkable expansion of the knowledge on reciprocal regulatory effect between various immune/inflammatory cells and T helper (Th) cell subsets including Th1, Th2, Th9, Th17, Th22, and follicular T-helper (Tfh) and regulatory T cells (Treg). Uncommitted naBve Th cells can be induced to differentiate to specific lineages according to the local cytokine milieu, towards Th or Treg phenotypes (1). The significance of Th17 immunity in acute, chronic and antibody-mediated allograft rejection is well known (2). However, Treg associated regulatory mechanisms have been implicated in tipping the balance in favor of tolerance rather than rejection (3). This review article summarizes the current knowledge on the contribution of T-helper subset cells in allograft rejection. The authors use a xenogeneic transplantation model to show the mechanisms by which Th1 cells participate in a allograft rejection. It also highlights that IL-12 or IFN-F knockout recipients showed faster acute vascular rejection than wildtype mice. Th2 cytokines inhibit Th1 responses and, as a result, can delay and even prevent acute rejection but seem to dominate during chronic rejection. The article also presents an extensive discussion of the involvement of Th17 in acute and chronic allograft rejection. The hallmark of Th17 cell-mediated allograft rejection is IL-17_s ability to recruit neutrophils which are one of the first inflammatory effector cells to infiltrate the allograft after transplantation and cause allograft damage. In addition a link between Th17 and alloimmunity particularly in the context of chronic lung allograft rejection is discussed. The final section of the review discusses the regulation of Th subsets by CD4+Foxp3+ Tregs in transplantation. It is well established that Tregs appear to be the Bmaster regulators[ that induce and maintain transplantation tolerance in experimental and clinical transplantation possibly by suppressing both Th1 and Th2 clones. Interestingly Th17 cells have the tendency to resist Treg-mediated suppression. The authors advocated that further studies are still needed to unravel the underlying mechanisms of these cells in the complex contexts of allograft rejection and tolerance and would facilitate devising strategies to achieve tolerance in the clinic.
近年来,人们对各种免疫/炎症细胞与辅助性T细胞(Th)亚群(包括Th1、Th2、Th9、Th17、Th22以及滤泡辅助性T细胞(Tfh)和调节性T细胞(Treg))之间相互调节作用的认识得到了显著的拓展。未确定的naBve - Th细胞可以根据局部细胞因子环境诱导分化为特定的谱系,向Th或Treg表型分化(1)。Th17免疫在急性、慢性和抗体介导的同种异体移植排斥反应中的重要性是众所周知的(2)。Treg相关的调节机制涉及到倾向于耐受而不是排斥的平衡(3)。这篇综述文章总结了目前关于t辅助亚细胞在同种异体移植排斥反应中的贡献的知识。作者使用异种移植模型来显示Th1细胞参与同种异体移植排斥反应的机制。它还强调IL-12或IFN-F敲除受体比野生型小鼠表现出更快的急性血管排斥反应。Th2细胞因子抑制Th1反应,因此可以延迟甚至防止急性排斥反应,但似乎在慢性排斥反应中占主导地位。文章还提出了Th17参与急性和慢性同种异体移植排斥反应的广泛讨论。Th17细胞介导的同种异体移植排斥反应的标志是IL-17_s招募中性粒细胞的能力,中性粒细胞是移植后第一批浸润同种异体移植物并引起同种异体移植物损伤的炎症效应细胞之一。此外,Th17与异体免疫之间的联系,特别是在慢性肺同种异体移植排斥反应的背景下进行了讨论。本综述的最后一部分讨论了CD4+Foxp3+ Tregs在移植中对Th亚群的调节。已经确定Tregs似乎是Bmaster调控因子[可能通过抑制Th1和Th2克隆在实验和临床移植中诱导和维持移植耐受]。有趣的是,Th17细胞有抵抗treg介导的抑制的倾向。作者认为,仍需要进一步的研究来揭示这些细胞在异体移植排斥和耐受的复杂背景下的潜在机制,并有助于制定在临床实现耐受的策略。
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引用次数: 581
Immune Profiles to Detect Heart Recipients at Risk of Development of Severe Infection 免疫谱检测心脏受者在严重感染发展的风险
Pub Date : 2012-11-01 DOI: 10.1097/00007890-201211271-00702
J. Carbone, N. D. Pozo, A. Gallego, N. Lanio, C. Rodríguez, J. Rodríguez-Molina, J. Navarro, J. Palomo, J. Fernández‐Yáñez, A. Villa, P. Muñoz, M. Ruiz, J. Hortal, K. Kotsch, F. Kern, E. Fernandez-cruz, E. Sarmiento
Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo . This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo . Murine Treg lines were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS). NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ( 99m TcO 4- ) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in mice by SPECT/CT using 99m TcO 4- . After 24-hours Treg-NIS cells were observed in the spleen and their localisation was further confirmed by organ-biodistribution studies and flow cytometry analysis. Moreover, we have demonstrated that this method of imaging can be utilised to image migration of Tregs with direct and indirect allo-specificity in a skin transplant model. The data presented here suggests that SPECT/CT can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models. study. heart Clinical follow-up: 6 months. intravenous antimicrobial therapy, with positive clinical compromise. Study points: pre-trasplant, day-7 and day-30 after transplant. The immunological study included humoral and cellular immunity markers of : adaptive and innate immunity: Serum IgG, IgA, IgM, IgG subclasses, C3, C4, factor B (Nephelometry), manose binding lectin (ELISA), specific antibodies after vaccination (anti-pneumococcal polysaccharide [anti-PPS], anti-HBs, [ELISA]), natural specific antibodies without vaccination (anti-cytomegalovirus, anti-haemophilus influenzae type B, anti-salmonella typhi, anti-varicella zoster and T, B, NK lymphocyte subsets (flow-cytometry). Results: 154 patients were analysed. (38.3%) severe infections during follow-up. Univariate single marker analysis: Patients who disclosed: Lower levels of IgG (day 7, p< 0.001), C4 (day 7, p=0.016), IgG (day 30, p=0.007), IgA (day 30, p=0.016), anti-PPS (day 30, p=0.003) and lower absolute counts of NK CD3-CD16/CD56+ (day 7, p=0.017), T-CD3+ (day 30, p=0.008), T-CD4+ (day 30, p=0.012) and T-CD8+ lymphocytes (day 30, p=0.003). of immune profiles severe infection risk: Day 7: IgG< mg/dl + cells/uL (OR 3.327, p< 0.001, specificity 88.5%, PPV 72%); day 30: IgG<
调节性T细胞(Tregs)在几年前被发现,是控制自身免疫性疾病和限制对外来抗原的免疫反应的关键。通过单光子发射计算机断层扫描(SPECT)对人体钠/碘同调体进行成像已被用于对体内各种细胞类型进行成像。本研究探讨了SPECT/CT成像是否可以用于可视化体内treg的迁移模式。用编码人碘化钠同体转运蛋白(NIS)的构建体逆转录转导小鼠Treg细胞系。在体外用99m高锝酸盐(99m TcO 4-)对表达自身特异性Tregs的NIS细胞进行特异性放射性标记,这些细胞暴露于放射性中不会影响细胞的活力、表型或功能。此外,采用99m tco4 -对过继转移的Treg-NIS细胞在小鼠体内进行SPECT/CT成像。24小时后,在脾脏中观察到Treg-NIS细胞,并通过器官生物分布研究和流式细胞术分析进一步证实其定位。此外,我们已经证明这种成像方法可以用于在皮肤移植模型中具有直接和间接同种异体特异性的treg迁移成像。本文提供的数据表明,SPECT/CT可以用于过继转移Treg的临床前成像研究,而不会影响Treg的功能和活力,从而允许在疾病模型中进行纵向研究。研究。临床随访:6个月。静脉抗菌药物治疗,有积极的临床妥协。研究点:移植前、移植后第7天和第30天。免疫学研究包括体液免疫和细胞免疫标志物:适应性免疫和先天免疫;血清IgG, IgA, IgM, IgG亚类,C3, C4,因子B(浊度法),甘露糖结合凝集素(ELISA),接种后的特异性抗体(抗肺炎球菌多糖[抗pps],抗hbs, [ELISA]),未接种的天然特异性抗体(抗巨细胞病毒,抗B型流感嗜血杆菌,抗伤寒沙门氏菌,抗水痘带状疱疹和T, B, NK淋巴细胞亚群(流式细胞术)。结果:对154例患者进行了分析。随访期间严重感染(38.3%)。单因素单标记物分析:IgG(第7天,p< 0.001)、C4(第7天,p=0.016)、IgG(第30天,p=0.007)、IgA(第30天,p=0.016)、抗- pps(第30天,p=0.003)水平降低,NK CD3-CD16/CD56+(第7天,p=0.017)、T-CD3+(第30天,p=0.008)、T-CD4+(第30天,p=0.012)和T-CD8+淋巴细胞(第30天,p=0.003)绝对计数降低。严重感染风险:第7天IgG< mg/dl + cells/uL (OR 3.327, p< 0.001,特异性88.5%,PPV 72%);第30天:IgG<
{"title":"Immune Profiles to Detect Heart Recipients at Risk of Development of Severe Infection","authors":"J. Carbone, N. D. Pozo, A. Gallego, N. Lanio, C. Rodríguez, J. Rodríguez-Molina, J. Navarro, J. Palomo, J. Fernández‐Yáñez, A. Villa, P. Muñoz, M. Ruiz, J. Hortal, K. Kotsch, F. Kern, E. Fernandez-cruz, E. Sarmiento","doi":"10.1097/00007890-201211271-00702","DOIUrl":"https://doi.org/10.1097/00007890-201211271-00702","url":null,"abstract":"Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo . This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo . Murine Treg lines were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS). NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ( 99m TcO 4- ) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in mice by SPECT/CT using 99m TcO 4- . After 24-hours Treg-NIS cells were observed in the spleen and their localisation was further confirmed by organ-biodistribution studies and flow cytometry analysis. Moreover, we have demonstrated that this method of imaging can be utilised to image migration of Tregs with direct and indirect allo-specificity in a skin transplant model. The data presented here suggests that SPECT/CT can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models. study. heart Clinical follow-up: 6 months. intravenous antimicrobial therapy, with positive clinical compromise. Study points: pre-trasplant, day-7 and day-30 after transplant. The immunological study included humoral and cellular immunity markers of : adaptive and innate immunity: Serum IgG, IgA, IgM, IgG subclasses, C3, C4, factor B (Nephelometry), manose binding lectin (ELISA), specific antibodies after vaccination (anti-pneumococcal polysaccharide [anti-PPS], anti-HBs, [ELISA]), natural specific antibodies without vaccination (anti-cytomegalovirus, anti-haemophilus influenzae type B, anti-salmonella typhi, anti-varicella zoster and T, B, NK lymphocyte subsets (flow-cytometry). Results: 154 patients were analysed. (38.3%) severe infections during follow-up. Univariate single marker analysis: Patients who disclosed: Lower levels of IgG (day 7, p< 0.001), C4 (day 7, p=0.016), IgG (day 30, p=0.007), IgA (day 30, p=0.016), anti-PPS (day 30, p=0.003) and lower absolute counts of NK CD3-CD16/CD56+ (day 7, p=0.017), T-CD3+ (day 30, p=0.008), T-CD4+ (day 30, p=0.012) and T-CD8+ lymphocytes (day 30, p=0.003). of immune profiles severe infection risk: Day 7: IgG< mg/dl + cells/uL (OR 3.327, p< 0.001, specificity 88.5%, PPV 72%); day 30: IgG<","PeriodicalId":23474,"journal":{"name":"Transplantation Journal","volume":"24 1","pages":"380"},"PeriodicalIF":0.0,"publicationDate":"2012-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75508298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endovascular Treatment for the Pseudoaneurysms Arising from Hepatic Artery after Liver Transplantation 肝移植术后肝动脉假性动脉瘤的血管内治疗
Pub Date : 2012-11-01 DOI: 10.1097/00007890-201211271-00751
C. Lee, A. Thorat, W. Lee
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引用次数: 2
Innate Recognition of Allogeneic Non-Self Induces Monocyte Differentiation to Mature Dendritic Cells In Vivo 体内同种异体非自体先天识别诱导单核细胞分化为成熟树突状细胞
Pub Date : 2012-11-01 DOI: 10.1097/00007890-201211271-00845
M. Oberbarnscheidt, Q. Zeng, A. Williams, R. Hoffman, D. Rothstein, Fadi G Lakkis
after is a response to non-physiological cell death (‚danger‘) rather than to allogeneic non-self. we tested the alternate hypothesis that the innate immune system distinguishes between self and allogeneic non-self, causing DC maturation and activation of the adaptive immune response. Methods: T, B and NK cell-deficient B6 Rag -/- gc -/- or WT CX3CR1- GFP +/- reporter mice in monocyte lineage cells express GFP syngeneic (B6) or allogeneic (Balb/c) vascularized heart grafts. Graft-infiltrating cells analyzed 1, 3, 5, 10, 21 and 42 days after transplantation (Tx) and the function of host-derived DC tested ex and in vivo Results: in the graft by day after were host monocytes (mono-DC). numbers (2-5 fold) in allo than syn grafts at early time points (days 1-10) and at later time points (days 21 42) in allografts. Mono-DC allografts higher proportion of mature cells (MHCII + CD80 + ), IL-12p40, allogeneic T cells in the MLR, endotoxin-free antigen (OVA) to TCR-tg CD4 + (OT-II) and CD8 + (OT-I) T cells early and late after Tx. In vivo depletion of monocytes with clodronate liposomes abrogated the proliferation of alloreactive 1H3.1 TCR-tg CD4 + T cells transferred to allograft recipients. Depletion of host CD11b + cells by diphtheria toxin (DT) CD11b-DTR bone marrow chimeras dramatically reduced T cell accumulation in heart allografts examined on day 15 after Tx while DT-treated WT bone marrow chimeras rejected their allografts by day 10 with evidence of heavy T cell infiltration. self and allogeneic Multimers of soluble peptide-major histocompatibilty complex (pMHC) molecules are used in basic as well as in clinic immunology. They allow a specific visualization, phenotype characterization and isolation of antigen- specific T cells from ex vivo samples. Adoptive transfer of antigen-specific T cells sorted by pMHC multimers is an effective therapeutic strategy for treatment of patients with malignancies or infectious diseases after transplantation. A new reversible pMHC multimer technology, called pMHC Histamer technology , was developed enabling a specific detection and isolation of antiviral T cells from peripheral blood mononuclear cells. The HLA-A02/CMVpp65 and HLA-A01/ADV5_Hexon Histamers were generated by coupling 6xHis-tagged pMHC molecules onto cobalt-magnetic beads. The specificity and sensitivity of the magnetic bead-based Histamers was evaluated by flow cytometry. Sorting of antiviral CD8 + cytotoxic T cells (CTLs) was performed by magnetic cell separation, followed by the monomerization of the pMHC Histamers in the presence of L-histidine. Sorted T cells were analyzed in phenotypical and functional assays. The reversible Histamers showed superior specificity and sensitivity (up to 99.5%). Antigen-specific T cells isolated by this technology gave an excellent purity of up to 99.6%. A rapid and complete disassembly of the T-cell surface-bound pMHC Histamers followed by the subsequent dissociation of the pMHC
After是对非生理性细胞死亡(危险)的反应,而不是对异体非自体的反应。我们测试了另一种假设,即先天免疫系统区分自我和异体非自我,导致DC成熟和适应性免疫反应的激活。方法:T, B和NK细胞缺陷B6 Rag -/- gc -/-或WT CX3CR1- GFP +/-报告小鼠在单核细胞谱系细胞中表达GFP同体(B6)或异体(Balb/c)血管化心脏移植物。移植后1、3、5、10、21和42天对移植物浸润细胞(Tx)进行分析,并在体外和体内检测宿主来源的DC的功能。结果:移植后1天移植物中有宿主单核细胞(mono-DC)。同种异体移植物早期时间点(1-10天)和后期时间点(21 - 42天)同种异体移植物的数量是同种异体移植物的2-5倍。同种异体单核细胞移植后,成熟细胞(MHCII + CD80 +)、IL-12p40、MLR中的同种异体T细胞、无内毒素抗原(OVA)对TCR-tg CD4 + (OT-II)和CD8 + (OT-I) T细胞的比例较高。在体内用氯代酸脂质体消耗单核细胞可消除同种异体受体移植的同种异体1H3.1 TCR-tg CD4 + T细胞的增殖。白喉毒素(DT) CD11b- dtr骨髓嵌合体消耗宿主CD11b +细胞后,在Tx后第15天检测心脏同种异体移植物中,CD11b- dtr骨髓嵌合体显著减少T细胞的积累,而DT处理的WT骨髓嵌合体在第10天排斥同种异体移植物,并有大量T细胞浸润的证据。可溶性多肽-主要组织相容性复合物(pMHC)分子的自体和异体多聚体在基础免疫学和临床免疫学中都有应用。他们允许特异性可视化,表型表征和抗原特异性T细胞从离体样品的分离。pMHC多聚体分选的抗原特异性T细胞过继转移是治疗恶性肿瘤或感染性疾病患者移植后的有效治疗策略。开发了一种新的可逆pMHC多聚体技术,称为pMHC组胺技术,能够从外周血单核细胞中特异性检测和分离抗病毒T细胞。HLA-A02/CMVpp65和HLA-A01/ADV5_Hexon组stamer是通过将6xhis标记的pMHC分子偶联到钴磁珠上生成的。流式细胞术评价磁珠基组stamer的特异性和敏感性。抗病毒CD8 +细胞毒性T细胞(ctl)的分选采用磁性细胞分离,然后在l -组氨酸存在下将pMHC组胺单体化。分类后的T细胞进行表型和功能分析。可逆性组stamer表现出优异的特异性和敏感性(高达99.5%)。通过该技术分离的抗原特异性T细胞纯度高达99.6%。快速和完全分解t细胞表面结合的pMHC组stamers,随后是pMHC的解离
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引用次数: 1
期刊
Transplantation Journal
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