Th1细胞和Th17细胞在多发性硬化和实验性变态反应性脑脊髓炎发生中的作用

多发性硬化(MS)是一种由效应性T细胞介导的中枢神经系统自身免疫性脱髓鞘疾病,其病因和发病机制迄今不明.实验性变态反应性脑脊髓膜炎(EAE)为MS的动物模型.传统观念认为Th1细胞是MS自身免疫反应中主要的效应性T细胞.然而,Th17细胞的发现使Th1细胞的核心作用受到挑战.     

神经小胶质细胞在EAE 脱髓鞘和髓鞘再生中的作用机制进展

炎性细胞浸润和脱髓鞘是中枢神经系统(CNS)的自身免疫性疾病---多发性硬化(MS)的主要病理特征,相关的病理研究多在其动物模型实验性自身免疫性脑脊髓膜炎(EAE)中开展。神经小胶质细胞(MG)是CNS 的主要免疫效应细胞,EAE 时它的激活在脱髓鞘和髓鞘再生中表现出复杂的作用。M1 型MG 是导致脱髓鞘的重要原因,抑制髓鞘再生;而M2型MG 可以促进髓鞘再生,抵抗脱髓鞘。本文综述MG 在EAE 脱髓鞘和髓鞘再生中的直接作用机制,及其通过星形胶质细胞产生的间接作用机制及进展。     

髓鞘修复与多发性硬化

多发性硬化（MS）是以中枢神经系统炎性脱髓鞘为特征的自身免疫性疾病,神经功能障碍与髓鞘和轴索损伤有关。MS动物模型研究认为：髓鞘修复是治疗MS极有前景的途径。中枢神经系统存在少突胶质细胞前体细胞（OPCs）,在髓鞘修复和再生过程起关键作用。由于MS病人OPC分化受抑制,因此,在髓鞘再生过程中调控OPCs分化是髓鞘修复的重点。另外,移植外源性的髓鞘形成细胞促进髓鞘修复和神经再生,是修复MS脱髓鞘和轴索损伤的重要途径。     

多发性硬化免疫机制研究新进展

多发性硬化（MS）是一种以中枢神经系统白质神经变性为特征的自身免疫性疾病,其确切的病因发病机制尚不清楚。目前认为是在易感基因的基础上,受环境因素的触发由CD4^＋T细胞介导的中枢神经系统的自身免疫性疾病,但其他免疫细胞（包括B细胞、CD8^＋T细胞等）也能通过诱导或调控MS患者中枢神经系统内的免疫应答过程而可能参与MS的发病。以往认为Th1／Th2型反应失衡是其关键致病因素,近年来随着对其研究的深入,提出许多新的观点,为多发性硬化的免疫机制及治疗策略研究提供了新方向。     

多发性硬化与B淋巴细胞趋化因子-1

多发性硬化(MS)是一种中枢神经系统炎症性疾病,其病理机制主要包括神经变性及炎症反应,而B淋巴细胞趋化因子-13(CXCL-13)被认为参与MS等自身免疫和炎症性疾病的发病过程.CXCL-13既通过与CXCR5结合表达于B淋巴细胞、辅助性T细胞等,又影响B细胞从而促进自身免疫反应并参与炎症反应,这为MS治疗的新型药物研究提供了理论基础.     

小胶质细胞的活化在实验性自身免疫性脑脊髓炎中的作用

多发性硬化( multiple sclerosis,MS)是一种常见的以中枢神经系统(central nervous system,CNS)炎性脱髓鞘病变为特征的自身免疫性疾病.MS的病因和发病机制非常复杂,由于病理取材的困难性,在体外建立了该病的动物模型-实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE).人MS及其动物模型EAE发病过程中大量炎性细胞入侵CNS并产生多种致炎因子,脑内微环境受到影响.诸多研究表明在EAE或MS发病中静息态小胶质细胞在浸润的T细胞及释放的细胞因子刺激下发生活化,但它们在EAE中的作用目前尚无统一意见.兹将小胶质细胞在EAE中的活化机制及其在炎症/免疫反应中的作用作一综述.     

不同B细胞亚群在多发性硬化中的作用

多发性硬化（MS）是一种以中枢神经系统（CNS）脱髓鞘及持续的炎症反应为特征的神经自身免疫性疾病。长期以来MS被认为是由T细胞介导的疾病,然而,临床上MS抗CD20 B细胞耗竭治疗（BCDT）效果出人意料,凸显了B细胞在MS中的重要作用。但随着BCDT在MS中的应用,治疗后的副作用也显现出来。随着人们对B细胞知识的不断加深,了解不同B细胞亚群在疾病中的不同作用或许是找到解决临床副作用的关键。已知B细胞发育过程中不同B细胞亚群对MS的相对贡献目前还只是部分阐明。为此,本文主要从B细胞发育过程中不同B细胞亚群在MS中的相对贡献进行阐述,为深入探讨B细胞在MS发病机制和临床治疗策略中的作用提供科学思路。     

多发性硬化症及实验性自身免疫性脑脊髓炎免疫疗法的研究进展

正多发性硬化症(MS)是一种慢性进行性中枢神经系统(CNS)脱髓鞘的炎症性自身免疫病,主要由自身反应性CD4+T细胞对髓鞘自身抗原发生免疫应答所致,自身反应性CD8+T细胞~([1])和B细胞~([2])等也参与免疫损伤作用。小鼠、大鼠或豚鼠的实验性自身免疫性脑脊髓炎(EAE)是目前最广泛使用的MS动物模型,与MS有相似的组织病理变化和疾     

T细胞亚群在MS和EAE发病机制中的研究进展

多发性硬化(multiple sclerosis, MS)是一种慢性进行性自身免疫性疾病, 其主要病理特征表现为以累及脑白质区域为主的中枢神经系统的炎性脱髓鞘以及中枢神经系统周围小血管炎性浸润。实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis, EAE)是MS研究中最常用的动物模型。目前认为MS主要由CD4+T细胞介导, 辅助性T细胞(helper T cell, Th)1和Th17在MS发病机制中起关键作用。但近年来多种研究表明CD8+T细胞、自然杀伤T细胞(natural killer T cell, NKT)和γδT细胞等T细胞亚群在该疾病中也起着非常重要的作用。文章对不同T细胞亚群在MS及EAE中研究的最新进展进行综述。     

T细胞在多发性硬化发病机制中作用的研究进展

多发性硬化（MS）是临床常见的炎性、脱髓鞘性中枢神经系统（CNS）退行性变,通常认为是T细胞介导的自身免疫性疾病,但其具体病因和发病机制尚不清楚.近年来研究表明,多个亚型的T细胞均参与了MS的发病及其病程的调控.其中包括CD4^＋Th1细胞、CD8^＋T细胞、Th17细胞、CD16＋γδ T细胞、Th2细胞、调节性CD4＋T细胞、NK T细胞、CD8＋调节性T细胞等,因而研究MS了发病机制具有重要意义.     

Immunoregulatory function of mesenchymal stem cells

Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non-mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA-incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno-mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell-to-cell interactions, but also by environmental factors shaping their phenotype and functions.     

Influences of the pia mater on the precursors of nerve cells

Summary In the developing cerebellum of 8-day old rats surgical lesions were made. During regeneration of the cerebellum the pia mater was found to penetrate inside the neural tissue. Partially differentiated Purkinje cells and granule cells, that were in close contact with the pial cells, were found atrophied. When the profilerative cells of external granular layer came into contact with the pial cells, they were reduced to a primitive type of epitheloid cells. In this instance epithelio-mesenchymal interaction was found deleterious to the precursors of neurons. However, when the epithelioid cells were freed from the contact with the pial cells by intervening basement membrane, they differentiated into ependymal cells. Such ependymal cells gave rise to small as well as large new ventriculer structures, and structures resembling chorioid plexus.This research was supported by NIH Research Grant NS08817-03. Acknowledgements are due to Sheila Anderson for histology and to Donna Whitehurst for photographic work.     

干细胞若干定义的相关探讨

背景：近10年来干细胞研究所取得的巨大进展,不仅影响和促进了生物学及其相关基础科学,而且还在医学、药物开发、农业等许多领域得到广泛的应用,目前已成为研究的热点问题。 目的：在干细胞的定义上还存在一些需要探讨的问题,明确定义将有利于干细胞研究的快速发展。 方法：回顾干细胞的发展和概念提出,特别是通过中英文权威定义的比较,提出作者的看法。 结果与结论：干细胞的定义上还存在一些问题值得探讨,特别是一些中英文表述不同影响了理解。例如,“多能干细胞”对应译成两个单词：Pluripotent Stem Cell和Multipotent Stem Cell,然而Pluripotent和Multipotent两个单词的英文意义不同。为了学术交流和沟通,作者提出将Pluripotent Stem Cell称为“万能干细胞”,而保留Multipotent Stem Cell为“多能干细胞”的定义。以上结论供广大同仁探讨,以利于抛砖引玉。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Genetic aspects of the immunomodulationg action of interferon

Laboratory of Antiviral Immunity, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. D. Solov'ev.) Translated from Byulleten' Éksperimentl'noioi Biologii i Meditsiny, Vol. 105, No. 4, pp. 459–461, April, 1988.     

Identification of a CD8α Dendritic Cell Subpopulation in Rat Spleen and Evaluation of Its OX-62 Expression

Rat spleen DC and bone marrow-derived DC were isolated and characterized by morphology and flow cytometry. We found a CD8α⁺ DC subpopulation representing 19–48% (27.4 ± 12.0) of total spleen DC. The OX-62 expression on total spleen DC was 41–59% (51.8 ± 7.5). Myeloid bone marrow-derived DC were negative for CD8α and OX-62. We demonstrated the coexpression of CD8α and OX-62 molecules, at least in a portion CD8α⁺ spleen DC. Both CD8α⁺ and CD8α⁻ spleen DC subpopulations separated by MACS were able to induce an in vivo primary immune response to OVA. The immune response induced by the CD8α⁻ DC subpopulation was higher (P < 0.05). We identified a CD8α⁺ DC subpopulation in rat spleen less effective in inducing an immune response than CD8α⁻ DC. Moreover, our results suggest the presence of DC subpopulations with different lineages in DC preparations based on OX-62 expression.     

Accessory phenotype and function of macrophages induced by cyclic adenosine monophosphate

Mature macrophages (Mph) differentiated in culture from normal human peripheral blood monocytes (Mo) exhibit low activity as accessory cells (antigen-presenting cells) in T lymphocyte stimulation. A test system was established based on mitogenicity to quantitate the accessory activity of Mph-derived cells and to follow its changes for several days. The system used accessory cells treated with the oxidative mitogen, sodium periodate. The cells were subsequently co-cultured with pooled human lymphocytes from a cryopreserved stock. DNA synthesis in these cells was used as an indicator of accessory activity. Mph could be converted within 5-6 days into highly active accessory cells if a continuous stimulus of exogenously added dibutyryl cyclic AMP (db-cAMP) was provided. Mph treated by db-cAMP retained a high degree of HLA-DR expression but typical Mph markers such as non-specific esterase, phagocytosis, and expression of Fc-receptors were down-regulated. Acid phosphatase and myeloperoxidase underwent only slight changes, while the monocyte marker 5'-nucleotidase remained undetectable. Morphologically, the cells rounded up and developed veils and dendritiform elongations. In contrast to dendritic cells, Mph-derived accessory cells retained the CD14 antigen characteristic of monocytes and Mph. It is concluded that Mph are able to respond to exogenous stimuli and to convert into a highly active accessory cell. This contrasts to the well-known state of the 'activated Mph' with respect to markers and function. Both states appear to be antagonistically controlled by intracellular second messengers, as the accessory cell phenotype is positively correlated with intracellular cyclic AMP increase, whereas Mph activation correlates with cyclic GMP increase.     

Human Osteogenic Sarcoma: Fine Structure of the Osteoblastic Type

The fine structure of representative regions of 13 osteoblastic osteogenic sarcomas was studied. These regions contained four morphologically distinguishable subtypes of osteoblastlike cells. In addition, fibroblastlike and chondroblastlike cells were present, along with multinucleated giant cells, leukocytes, macrophagelike cells, and small populations of histogenetically unclassifiable (but probably neoplastic) cells.

The morphologic evidence was compatible with the view that the variations in appearance among the subgroups of osteobl astlike cells reflected differences in maturation and differentiation of these cells. In at least one subgroup, the morphologic findings suggested that the ceils were capable of manufacturing a secretory product. The multinucleated giant cells occurring in genuine tumor areas appeared to be closely related to neoplastic osteoblasts.

The presence of chondroblastlike cells in the tissues illustrates that cells with a diverging differentiation can occur in an osteoblast-dominated cell population. This agrees with the view that the neoplastic cells originate from a mesenchymal stem cell with potential for multifaceted differentiation.     

Trypanosoma cruzi calreticulin: In vitro modulation of key immunogenic markers of both canine tumors and relevant immune competent cells

Recombinant calreticulin from Trypanosoma cruzi (rTcCalr), the parasite responsible for Chagas’ disease, binds to Canine Transmissible Venereal Tumor (CTVT) cells from primary cultures and to a canine mammary carcinoma cell line. A Complement-binding assay indicated that interaction of the first component C1q with these tumor cells operated independently of the rTcCalr-presence. This apparent independence could be explained by the important structural similarities that exist among rTcCarl, endogenous normal canine and/or mutated calreticulins present in several types of cancer. In phagocytosis assays, tumor cells treated with rTcCalr were readily engulfed by macrophages and, co-cultured with DCs, accelerated their maturation. In addition, DCs maturation, induced by tumor cells co-cultured with rTcCalr, activated T cells more efficiently than DCs, treated or not with LPS. In an apparent paradox, a decrease in MHC Class I expression was observed when these tumor cells were co-cultivated with rTcCalr. This decrease may be related to a down regulation signaling promoting the rescue of MHC I. Possibly, these in vitro assays may be valid correlates of in vivo sceneries. Based on these results, we propose that rTcCalr improves in vitro the immunogenicity of two widely different tumor cell lines, thus suggesting that the interesting properties of rTcCalr to boost immune responses warrant future studies.     

雪峰虫草对DC-CIK增殖及HepG-2细胞杀伤作用的实验研究

目的:研究雪峰虫草对DC-CIK细胞增殖及肝癌Hep G-2细胞杀伤作用。方法:常规分离健康人外周血单个核细胞并诱导生成DC细胞和CIK细胞,将DC细胞与CIK细胞按1∶5共培养7 d后给药组加入不同浓度的雪峰虫草水提取物,第10天观察形态并计数各组DC-CIK细胞;收集培养第10天的DC-CIK细胞作为效应细胞,对数生长期Hep G-2肝癌细胞作为靶细胞,使Hep G-2∶DC-CIK靶效比为1∶5,cck-8法检测DC-CIK对Hep G-2的杀伤率。结果:雪峰虫草水提物组对DC-CIK有显著的促增长作用,其作用的最佳浓度为0.1 mg/ml。雪峰虫草诱导的DC-CIK细胞对肝癌Hep G-2细胞的杀伤作用优于常规方法培养的DC-CIK细胞;常规方法培养的DC-CIK细胞加雪峰虫草与常规方法培养的DC-CIK细胞对肝癌Hep G-2细胞的杀伤作用无显著性差异,雪峰虫草体外直接杀伤肝癌Hep G-2细胞的作用不明显。结论:雪峰虫草通过促进DC-CIK细胞增殖而增强其杀伤肝癌Hep G-2细胞的作用。