反义肽核酸下调树突状细胞CCR7基因表达及意义

肽核酸（PNA）是一种新型核酸类似物。树突状细胞（DCs）是功能最强的抗原提呈细胞，DCs从外周迁移到淋巴组织的T细胞区完成抗原递呈并激活初始T细胞。目前认为DCs向淋巴组织的迁移动力主要通过趋化因子作用于DCs趋化因子受体CCR7这条途径。我们通过反义PNA抑制体外培养的大鼠DCs CCR7的表达及趋化活性，探讨其在调节免疫反应方面的理论意义。     

DC诱导的抗肿瘤免疫及其在前列腺癌中的应用

树突状细胞 (Dendriticcell,DC)是目前已知体内功能最强的专职的抗原递呈细胞 ,DC表面持续表达的MHC II类分子和B7分子能有效地与肿瘤抗原结合并递呈肿瘤抗原 ,DC还可以作为肿瘤免疫反应的启动因素 ,在肿瘤免疫的产生和调节中发挥关键作用。     

DC诱导的抗肿瘤免疫及其在前列腺癌中的应用

树突状细胞(Dendritic cell，DC)是目前已知体内功能最强的专职的抗原递呈细胞，DC表面持续表达的MHC-Ⅱ类分子和B7分子能有效地与肿瘤抗原结合并递呈肿瘤抗原，DC还可以作为肿瘤免疫反应的启动因素，在肿瘤免疫的产生和调节中发挥关键作用。     

树突状细胞与移植免疫耐受

树突状细胞 (ＤＣ)是目前已知功能最强的专职抗原递呈细胞。它最大的特点是捕获外来抗原 ,迁移至引流淋巴结 ,发育成熟并递呈抗原 ,启动和诱导Ｔ细胞分化产生免疫反应或直接激活Ｂ细胞及产生免疫记忆[1] ,因此ＤＣ是免疫应答的始动者。本文就近两年ＤＣ与免疫耐受的关系作一综述。一、树突状细胞亚群ＤＣ是一异质的细胞群体 ,其异质性主要表现在不同的细胞起源、不同的成熟状态和功能方面[2 ] 。细胞起源和成熟程度差异决定着ＤＣ的不同功能 ,这与免疫耐受诱导有着十分密切的关系。根据ＤＣ表面蛋白质分子 ,可将源于小鼠骨髓和胸腺或淋巴器…     

树突状细胞、调节性T细胞在肾小球肾炎中的研究进展

肾小球肾炎(GN)是以肾小球损害为主的变态反应性炎症,是一种较为常见的疾病.树突状细胞(DCs)作为专职抗原递呈细胞(APC)具有强大的抗原递呈及及免疫调节能力,在机体免疫反应中起重要作用.最近的研究揭示DCs是T细胞在肾淋巴结中的活化剂,并且它们在肾脏中相互作用.这种相互作用通过细胞因子和趋化因子来调控,维持肾小管间...     

树突状细胞对抗原的摄取、处理与递呈机制

近年来器官移植在修复重建领域获得较大的发展,应用异体移植进行组织器官缺损的再造成为整形外科新的治疗手段.目前器官移植最大的障碍是异体排斥反应,要根本解决免疫排斥问题、保持移植组织的长期存活需从免疫反应发生的内部机制入手,其中抗原递呈是免疫激活的必要环节.树突状细胞(dendritic cells,DC)是迄今发现功能最强的抗原递呈细胞(an tigen presenting cells,APC),其功能独特之处在于全身所有APC中唯有DC才能激活初始型T细胞[1],它是识别内外抗原、调节免疫功能、维持机体稳定的关键因素,在机体免疫系统中处于中心地位,与移植免疫具有密切的关系.DC递呈供体抗原是免疫排异反应发生的首要步骤,深入认识其抗原递呈的过程与机制对揭示移植免疫的内在本质、解决异体排斥难题具有重要意义.     

慢性肾功能不全患者的树突状细胞功能异常研究现状

免疫功能异常是慢性肾功能不全患者高死亡率的隐患之一.近年越来越多的研究开始关注作为抗原提呈细胞的树突状细胞在维系固有免疫和适应性免疫之间的作用.本文对近年国内外相关文献进行综合与概括,提示此类患者由树突状细胞表达的多种相对特异性表面标志(如趋化因子受体、HLA、共刺激分子)及细胞因子存在异常.结果表明慢性肾功能不全患者的免疫缺陷与树突状细胞功能异常有关.     

霉酚酸酯对未成熟树突状细胞抗原递呈功能的影响

目的研究霉酚酸酯(MMF)在体外对小鼠未成熟树突状细胞抗原递呈功能的影响。方法在骨髓来源未成熟树突状细胞的培养过程中加入MMF，表型鉴定之后，做抗原递呈功能分析，观察抗原特异性增殖反应、混合淋巴细胞反应以及T淋巴细胞抗原特异性低反应性。结果以MMF处理的未成熟树突状细胞向T淋巴细胞递呈可溶性抗原的能力减弱，在同基因型的树突状细胞和T淋巴细胞接触条件下不能刺激致敏T淋巴细胞的有效增殖；MMF处理的树突状细胞在体外的同种混合淋巴细胞培养反应中能够维持树突状细胞于未成熟状态，不能充分活化CD4^ T淋巴细胞和诱发TH1反应，诱导了T淋巴细胞对同种抗原的低反应性；MMF处理的树突状细胞诱导的T淋巴细胞低反应性具有同种抗原特异性。结论在体外培养过程中给予MMF干预能够降低未成熟树突状细胞的抗原递呈能力，增强同种未成熟树突状细胞的免疫耐受诱导作用。     

次黄嘌呤单核苷酸脱氢酶抑制剂对人外周髓样树突状细胞趋化、迁移和吞噬功能的影响研究

目的 探讨次黄嘌呤单核苷酸脱氢酶抑制剂(Inosine monophosphate dehydrogenase inhibitor,IMPDHI)对人外周髓样树突状细胞(Myeloid dendritic cells,MDC)趋化、迁移、吞噬功能的影响.方法 新鲜外周血单个核细胞来源于健康志愿者(N=15).实验组加入不同浓度IMPDHI,流式细胞仪分析MDC表面趋化因子受体表达水平.于transwell小室实验中,加入不同的化学因子,经Lin-1/CD11c/HLA-DR染色后,流式细胞仪计数,以迁移细胞的百分比表示迁移能力.分离树突状细胞抗原-1+(Blood dendritic cell antigen-1,BDCA-1+)细胞后,以甘露糖受体作为介导,流式细胞仪测定BDCA-1+细胞中FITC标记的右旋糖酐的荧光值表示吞噬能力.结果 (1)趋化、迁移功能:与对照组相比,实验组MDC的趋化因子受体CCR1表达水平明显升高(17.02±3.23～30.63±9.13,P＜0.05);CCR3表达水平(10.26±2.25～5.81±0.97,P＜0.05)和CCR7表达水平(9.56±1.84～5.18±0.60,P＜0.05)明显下降.实验组MDC对炎性化学因子CCL2、CCL3、CCL4、CCL7、CXCL12的趋化能力明显增强(P＜0.05),对淋巴器官性化学因子CCL19、CCL20、CCL21、CXCL11的趋化能力无明显改变(P＞0.05).(2)吞噬功能:实验组MDC的吞噬能力明显强于对照组(P＜0.05).结论 IMPDHI增强MDC吞噬抗原的能力,通过提高MDC炎性化学因子受体的表达水平和增强其对炎性化学因子的趋化能力,抑制MDC对淋巴器官的趋化、迁移能力.     

树突状细胞体内迁移机制研究进展

树突状细胞(Dendritic cells,DC)是目前已知功能最强的专职性抗原提呈细胞(Antigen-presenting cells,APC),其抗原能力是巨噬细胞的10～100倍[1].树突状细胞能否发挥其强大的功能,与其在机体迁移机制密切相关.骨髓来源的树突状细胞前体经血液到达外周非淋巴组织后,在外周抗原的刺激下捕获抗原,与自身合成的MHC-Ⅱ类分子结合成抗原-MHC-Ⅱ类分子复合物表达于细胞膜表面[2].此后细胞继续迁至淋巴结T区,将抗原提呈给T细胞,激发T细胞细胞毒作用.这个过程伴有树突状细胞由未成熟向成熟转化,并有多种因子对整个过程进行调控,现将目前研究状况做一简要介绍.     

Migratory responses of murine hepatic myeloid, lymphoid-related, and plasmacytoid dendritic cells to CC chemokines

Dendritic cell (DC) trafficking is regulated by chemokine receptor expression and responsiveness to chemokines. The authors compared CC chemokine receptor (CCR) expression by mouse liver myeloid, "lymphoid-related," and plasmacytoid DC subsets and their responsiveness to CC chemokines. CCR mRNA expression by liver DC subsets was evaluated by RNase protection assay. In vitro migration of the DC in response to recombinant murine CC chemokines was assayed using Transwell chambers. Immature liver DC did not respond to any CC chemokines tested, despite expression of mRNA encoding appropriate receptors for their ligands. CCR7 expression by each liver DC subset was strongly enhanced in response to maturation. The migratory capacity of liver plasmacytoid DC was similar to that of liver myeloid and lymphoid-related DC. These findings suggest that targeting of CCR7 and its ligands may be a potential approach for manipulation of liver DC trafficking to secondary lymphoid tissue after liver transplantation.     

Murine neuroblastoma attenuates dendritic cell cysteine cysteine receptor 7 (CCR7) expression

Background/Purpose

Dendritic cell (DC) migration from tumors to T-cell priming sites is critical in developing antitumor cytotoxicity. Cysteine cysteine receptor 7 (CCR7), a promigratory chemokine receptor, regulates DC recruitment to secondary lymphoid organs. Tumors may inhibit CCR7 expression to evade immunodetection. Previous work implicates impaired DC migration as a critical defect in immunity to neuroblastoma (NB). However, the mechanism has yet to be defined. We hypothesize that NB abrogates DC CCR7 expression and signaling, leading to decreased antitumor immunity.

Methods

A/J mice (N = 36) were injected with saline (control) or murine NB (TBJ) and bone marrow-derived DC were isolated at 7, 14, and 28 days. CCR7 expression was analyzed by polymerase chain reaction, Western blot, and flow cytometry. Cytometry data were analyzed using the paired Student's t test.

Results

Dendritic cells isolated from mice with NB had a 60% increase in CCR7 protein expression by flow cytometry compared with control mice at day 7. However, there was a 43% downregulation of CCR7 expression by DC from tumor-bearing mice compared with controls 2 weeks postinoculation (P < .005). These observations were confirmed by polymerase chain reaction and Western blot analysis.

Conclusion

Neuroblastoma initially upregulates CCR7 expression by DC. However, with tumor progression, this chemokine is downregulated, likely leading to impaired DC migration. Immunotherapeutic strategies to bypass or augment CCR7-dependent DC trafficking may improve survival for patients with aggressive disease.     

树突细胞的免疫调节功能及其影响因素

树突细胞(DC)是体内功能最强的专职抗原呈递细胞,它在调控机体对自身或非自身抗原产生适当的免疫应答方面起非常重要的作用。DC是一群异质性的细胞,不同亚型的DC具有不同的功能。组织微环境、DC的成熟状态、DC表面的免疫分子以及局部组织基质细胞(如肝星状细胞)等与DC的功能有关。通过改变DC表面的一些关键分子的表达能够调控DC诱导的免疫反应。阐明决定DC诱导免疫耐受功能的关键分子以及DC选择性触发T细胞向辅助性T细胞(Th)1、Th2、Th17、调节性T细胞等不同方向分化的关键因素对寻找用新的方法来调控机体免疫反应具有重大意义。     

Dendritic cells generated from patients with androgen-independent prostate cancer are not impaired in migration and T-cell stimulation

BACKGROUND: Dendritic cell (DC)-based vaccination has been investigated as immunotherapy for several types of cancer. A potential drawback to vaccination with autologous monocyte-derived DCs (MoDCs) could be that MoDCs from patients are functionally impaired. In case of androgen-independent prostate cancer (CaP), the cancer itself, diverse prior therapies, and the hormone manipulation may affect the immune system. METHODS: MoDCs from patients suffering from androgen-independent CaP were generated according to a clinically applicable protocol to evaluate the phenotype, maturation capacity, migration, and T-cell stimulation of these cells compared with those generated from tumor-free donors. RESULTS: MoDCs generated from CaP patients could be fully matured and efficiently migrated towards the chemokine CCL21. They had a strong potency to activate allogeneic CD4+ and CD8+ T-cells and to present antigens to specific CTL. CONCLUSIONS: Our data suggest that MoDCs from patients with androgen-independent CaP are functionally intact and hence qualify as cellular vaccines for immunotherapy of advanced stage CaP.     

Dendritic cells in the kidney

Dendritic cells (DC) in nonlymphoid organs function at the crossroads of innate and adaptive immunity, self-tolerance, and tissue homeostasis. This review provides an overview of the study of DC in the kidney, tracing its history leading to the current knowledge of the origins, migration, and function of renal DC. Together, these studies suggest that renal DC play a critical role in the health and disease of the kidney, opening the way to direct targeting of renal DC for therapeutic benefit.     

The contribution of dendritic cells to immune responses against urological cancers

Dendritic cells (DC) play an essential role in initiating and directing primary immune responses. Their antigen uptake, migration, and interaction with T lymphocytes are regulated. Immunohistological studies of renal cell carcinomas, prostatic carcinomas, and transitional cell carcinomas suggest that these malignancies fail to recruit or activate DC. Tumor mediated inhibition of DC function may also occur by a variety of mechanisms. These data provide a rationale for the use of DC for active tumor immunotherapy. Initial data suggests that DC may help generate effective T lymphocyte responses against prostate cancer antigens and optimization of DC preparations, tumor antigenic material, and vaccination schedules are now priorities for therapeutic programs.     

基因修饰的树突状细胞疫苗诱导抗肿瘤免疫

树突状细胞是目前已知最有效的专职抗原提呈细胞,能诱导针对肿瘤的特异性细胞毒性T淋巴细胞反应,在抗肿瘤免疫中发挥着重要作用.运用树突状细胞的这一特性制备的肿瘤疫苗在体外和体内实验都已证明其抗肿瘤效应.近年来,基因修饰的树突状细胞疫苗由于其更出色的抗肿瘤效应成为研究的热点.本文就目前基因修饰的树突状细胞疫苗的研究现状,包括...     

Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival

Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival.     

小鼠骨髓未成熟树突状细胞体外扩增及鉴定

目的建立体外大量扩增小鼠未成熟树突状细胞(DC)的方法，从形态学、免疫表型和细胞功能试验等方面予以鉴定。方法制备小鼠骨髓细胞，分别用不同剂量重组小鼠粒细胞巨噬细胞集落刺激因子(rmGM—CSF)培养，7d后收集悬浮细胞进行扫描电镜观察和免疫表型鉴定，并行混合淋巴细胞反应，观察其诱导未致敏T淋巴细胞增殖的情况。结果小剂量rmGM—CSF培养获得的DC(GM^low DC)具有DC的典型特征，细胞表面高表达CD11c，低表达CD40、I—A／1-E，不表达B7—1，与大剂量rmGM—CSF培养获得的DC(GM^high DC)相比，其体外刺激未致敏T淋巴细胞增殖的能力较弱。结论本实验中获得的GM^low DC形态上具有DC的典型特征，在细胞表型、细胞功能试验上具有未成熟的特性，说明所建立的培养未成熟DC的方法是可行的；rmGM—CSF的剂量与细胞的成熟程度相关，一般说来，较大剂量的rmGM—CSF诱导生成的细胞以成熟。DC为主，小剂量rmGM—CSF诱导生成的细胞以未成熟DC为主。