肝星状细胞研究进展

肝星状细胞(hepatic stellate cells，HSCs)是肝脏的非实质细胞之一，以前也称为贮脂细胞(fat-storing cells)、Ito细胞(Ito cells)、脂细胞(1ipocytes)、间质细胞(interstitial cells)、窦周细胞(peri-sinusoidal cells)或维生素A储存细胞(vitamin A-storing cells)等，其位于Disse间隙内，形态不规则，胞体呈卵圆形，其核周部分包埋在邻近肝细胞的隐窝内，     

细胞移植及细胞联合移植修复脊髓损伤的研究进展

<正>脊髓损伤(spinal cord injury,SCI)是中枢神经系统的严重创伤,其发病率和致残率呈逐年增高的趋势,而且给社会和家庭带来沉重的负担[1],是近年医学研究的热点难题之一。随着神经组织工程技术的发展,利用细胞移植和细胞联合移植修复SCI成为近年研究的热点。目前可供选择的移植细胞类型有神经干细胞(neural stem cells,NSCs)、施万细胞(schwann cells,SCs)、胚胎干细胞(embryonic stem cells,ESCs)、嗅鞘细胞(olfactory ensheating cells,OECs)、骨髓间充质干细胞(bone mesenechymal stem cells,BMSCs)、少突胶质     

NK细胞和NKT细胞在病毒性肝炎中的作用

NK细胞(Natural killer cells)和NKT细胞(Natural killer T cells)参与机体的天然免疫反应。NK细胞在肝炎病毒感染的早期免疫反应中起到重要作用,而慢性病毒性肝炎患者NK细胞功能降低。另外,动物实验显示NKT细胞可致肝组织损伤并能抑制肝炎病毒的复制。因此通过调节NK细胞和NKT细胞的功能治疗病毒性肝炎将有可能成为一种新的策略。     

与CIK细胞共培养降低K562/ADR来源DC细胞MDR-1基因表达

细胞因子诱导的杀伤细胞(eytokine induced killer cell,CIK)是一种高效、新型的免疫活性细胞.树突细胞(dendritic cells,DC)是目前发现的功能最强的抗原呈递细胞(APC),它通过处理、呈递抗原,介导机体的免疫应答[1].     

树突状细胞引流淋巴结归巢的研究进展

树突状细胞(dendritic cells,DCs)是目前已知的体内功能最强的专职性抗原提呈细胞(professional antigen-present-ing cells,pAPC),在引发和调节机体的免疫反应中起着重要作用。树突状细胞最重要的功能是摄取、加工处理、提呈抗原,并刺激初始T细胞(naive T cells)活化、增殖,从而激发机体的免疫应答。DCs这一功能是在体内迁移过程中发挥的,其中DCs归巢至引流淋巴结被认为是激发免疫应答的关键步骤之一。本文将就近年来DCs归巢至引流淋巴结的研究进展作一综述。     

NK细胞可溶性KIR3DL1分子检测双夹心ELASA的建立

<正>自然杀伤细胞(natural killer cells,NK细胞)是固有免疫中一类十分重要的淋巴细胞,约占循环淋巴细胞总数的15%。目前根据CD56和CD16的表达水平可将NK细胞分为CD56hi、CD56dim和CD56-CD16+3个亚群。由于NK细胞不表达T细胞受体(T cell receptor,TCR)和B细胞受体(B cell receptor,BCR),如何区别"自己"和"非己"一直是个     

放射状胶质细胞的研究进展

脊椎动物中枢神经系统(central neural system,CNS)发育过程中,有一类细胞与CNS的发育密切相关一神经干细胞(neural stem cells,NSCs),目前已知的NSCs主要有3种:神经上皮细胞、放射状胶质细胞(radial glial cells,RGCs)、基祖细胞.     

Tfh、Tfr细胞表达情况与HSP患儿肾脏受累情况的关系

目的 研究过敏性紫癜(Henoch Sch(o)nlein purpura,HSP)患儿外周血滤泡调节性T细胞(follicular regulatoryT cells,Tfr细胞)、滤泡辅助性T细胞(follicular helperT cells,Tfh细胞)的表达情况,及其与肾脏受累的关系.方法 选取我院2017...     

树突状细胞影响肝移植

据Supter TL[Hepatology，2007，46（6）：2021-2031]报道，肝脏树突状细胞对肝移植有重要影响。 树突状细胞（dendritic cells，DC）是近年来倍受人们关注的专职抗原呈递细胞（antigen presenting cells，APC），能摄取、加工及呈递抗原，启动T淋巴细胞介导的免疫反应。     

骨骼肌组织工程种子细胞来源的研究进展

构建组织工程骨骼肌的种子细胞有肌卫星细胞、成肌细胞、胚胎干细胞、间充质来源的干细胞(包括骨髓来源干细胞、羊水来源干细胞、脂肪来源干细胞等).不同来源的种子细胞在体内、外均能向肌细胞系分化,或与肌源系细胞融合,表达肌源系细胞表面抗原,参与肌纤维的修复.这些种子细胞均有望构建组织工程化骨骼肌.对目前骨骼肌组织工程种子细胞来源进行综述. Abstract： Different cells could be utilized as seed cells in the construction of tissue-engineered skelet al muscle, which include satellite stem cells, myohlasts, embryonic stem cells and mesenchymal stem cells includ-ing bone marrow-derived stem cells, amniotic fluid-derived stem cells, and adipose tissue-derived stem cells. Seed cells from different origins are capable of trans-differentiating into myogenic cells or fusing with myogenic cells, expressing the surface antigen of sarcogenic cells, and participating in the regeneration of muscle fiber, both in vivo and ex vivo. This review gives a summarization of the recent progress in the research on seed cell source in skelet al muscle tissue engineering.     

微环境中调节性T细胞与乳腺癌关系的研究进展

乳腺癌肿瘤免疫微环境是乳腺癌细胞与免疫细胞、免疫分子之间相互作用的场所,对乳腺癌的发生发展及预后产生重要影响.调节性T细胞(Tregs)作为一类具有免疫抑制功能的T淋巴细胞亚群,可通过抑制T细胞的功能,抑制机体抗肿瘤免疫,促进肿瘤的发生发展.研究显示,乳腺肿瘤免疫微环境中Tregs在乳腺癌发生、发展以及靶向治疗中发挥着重要作用.     

Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis

Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co‐evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4⁺CD45RO⁺forkhead box protein 3 (FoxP3)^high and CD4⁺CD25^highFoxP3⁺CD95^high phenotype and of non‐regulatory CD4⁺CD45RO⁺FoxP3^med T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA‐4), lymphocyte‐activation gene 3 (LAG‐3), programmed death 1 (PD‐1) and glucocorticoid‐induced tumour necrosis factor receptor (GITR), suggesting a cell‐to‐cell contact mechanism with dendritic cells. Furthermore, higher IL‐10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients’ peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4⁺CD38⁺). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell‐to‐cell contact with dendritic cells and interleukin (IL)‐10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.     

调节性T细胞相关负性分子与感染免疫

调节性T细胞通过免疫抑制与免疫耐受机制影响疾病的发展。与调节性T细胞相关的CTLA-4、PD-1等负性分子在调节性T细胞的调节功能中起重要作用。本文拟对CTLA-4、PD-1和调节性T细胞的关系以及在病毒感染、细菌感染、寄生虫感染等免疫病中的调节机制作一综述。     

Antibody blocking of MHC II on human activated regulatory T cells abrogates their suppressive potential

Natural regulatory CD4(+)CD25(+)Foxp3(+) T cells control peripheral immune responses. Freshly isolated regulatory T-cell populations are regarded as being unable to suppress the proliferation of strongly stimulated effector T cells. We now provide evidence that it is not the strength of the proliferative signal to effector T cells but activation and accessibility of regulatory T cells that determine whether suppression may occur. Human regulatory T cells were initially cocultured with allogeneic monocyte-derived dendritic cells for a short time and were then rendered accessible for effector T cells by removal of the dendritic cells. That way activated regulatory T cells effectively suppressed the proliferation of autologous effector T cells which was strongly driven by cell-sized Dynabeads coated with CD3/CD28 antibodies. Although regulatory T cells are known to display MHC II molecules and to upregulate their expression along with activation, a role of MHC II molecules in forming the contact to effector T cells was not yet envisaged. However, blocking of MHC II on activated regulatory T cells abrogated their suppressive potential. It should not be excluded that self-MHC molecules on physically accessible activated regulatory T cells arrange the contact to effector T cells.     

局部浸润Foxp3+调节性T细胞在结直肠癌中的研究进展

肿瘤微环境中的免疫状态对肿瘤患者的预后意义重大.调节性T细胞(Tregs)是造成肿瘤免疫逃逸和肿瘤免疫治疗失败的关键因素.Foxp3是Tregs细胞重要的胞内信号标记,并在Tregs细胞的发育和功能中起关键作用.大多数肿瘤中局部浸润Tregs细胞的升高往往提示预后不良,但是在结直肠癌中Tregs细胞的预后意义各家报道仍有分歧.Tregs细胞的多态性包括表型、功能等,可能是造成这一矛盾的原因之一,但是缺乏一种更具特异性的标记或者标准化的检测手段也可能是造成这一现象的原因.     

Fibroblastic reticular cells at the nexus of innate and adaptive immune responses

Lymphoid organs guarantee productive immune cell interactions through the establishment of distinct microenvironmental niches that are built by fibroblastic reticular cells (FRC). These specialized immune‐interacting fibroblasts coordinate the migration and positioning of lymphoid and myeloid cells in lymphoid organs and provide essential survival and differentiation factors during homeostasis and immune activation. In this review, we will outline the current knowledge on FRC functions in secondary lymphoid organs such as lymph nodes, spleen and Peyer's patches and will discuss how FRCs contribute to the regulation of immune processes in fat‐associated lymphoid clusters. Moreover, recent evidence indicates that FRC critically impact immune regulatory processes, for example, through cytokine deprivation during immune activation or through fostering the induction of regulatory T cells. Finally, we highlight how different FRC subsets integrate innate immunological signals and molecular cues from immune cells to fulfill their function as nexus between innate and adaptive immune responses.     

Regulatory T cells and T helper 17 cells in viral infection

CD4⁺ T cells are the central element of the adaptive immune responses and protect the body from a variety of pathogens. Starting from naive cells, CD4⁺ T cells can differentiate into various effector cell subsets with specialized functions including T helper (Th) 1, Th2, Th17, regulatory T (Treg) and T follicular helper (Tfh) cells. Among them, Tregs and Th17 cells show a strong plasticity allowing the functional adaptation to various physiological and pathological environments during immune responses. Although they are derived from the same precursor cells and their differentiation pathways are interrelated, the terminally differentiated cells have totally opposite functions. Studies have shown that Tregs and Th17 cells have rather complex interplays in viral infection: Th17 cells may contribute to immune activation and disease progression while Tregs may inhibit this process and play a key role in the maintenance of immune homoeostasis, possibly at the cost of compromised viral control. In this review, we take respiratory syncytial virus (RSV), hepatitis B virus (HBV)/hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections as examples to discuss these interplays and their impacts on disease progression in viral infection.     

Activated CD4+ CD25+ T cells suppress antigen-specific CD4+ and CD8+ T cells but induce a suppressive phenotype only in CD4+ T cells

CD4(+) CD25(+) regulatory T cells are increasingly recognized as central players in the regulation of immune responses. In vitro studies have mostly employed allogeneic or polyclonal responses to monitor suppression. Little is known about the ability of CD4(+) CD25(+) regulatory T cells to suppress antigen-specific immune responses in humans. It has been previously shown that CD4(+) CD25(+) regulatory T cells anergize CD4(+) T cells and turn them into suppressor T cells. In the present study we demonstrate for the first time in humans that CD4(+) CD25(+) T cells are able to inhibit the proliferation and cytokine production of antigen specific CD4(+) and CD8(+) T cells. This suppression only occurs when CD4(+) CD25(+) T cells are preactivated. Furthermore, we could demonstrate that CD4(+) T-cell clones stop secreting interferon-gamma (IFN-gamma), start to produce interleukin-10 and transforming growth factor-beta after coculture with preactivated CD4(+) CD25(+) T cells and become suppressive themselves. Surprisingly preactivated CD4(+) CD25(+) T cells affect CD8(+) T cells differently, leading to reduced proliferation and reduced production of IFN-gamma. This effect is sustained and cannot be reverted by exogenous interleukin-2. Yet CD8(+) T cells, unlike CD4(+) T cells do not start to produce immunoregulatory cytokines and do not become suppressive after coculture with CD4(+) CD25(+) T cells.     

Immune regulation by non‐lymphoid cells in transplantation

Regulatory cells play a crucial role in the induction and maintenance of tolerance by controlling T cell as well as B and natural killer (NK) cell‐mediated immunity. In transplantation, CD4⁺CD25⁺forkhead box P3⁺ T regulatory cells are instrumental in the maintenance of immunological tolerance, as are several other T cell subsets such as NK T cells, double negative CD3⁺ T cells, γδ T cells, interleukin‐10‐producing regulatory type 1 cells, transforming growth factor‐β‐producing T helper type 3 cells and CD8⁺CD28^‐ cells. However, not only T cells have immunosuppressive properties, as it is becoming increasingly clear that both T and non‐T regulatory cells co‐operate and form a network of cellular interactions controlling immune responses. Non‐T regulatory cells include tolerogenic dendritic cells, plasmacytoid dendritic cells, mesenchymal stem cells, different types of stem cells, various types of alternatively activated macrophages and myeloid‐derived suppressor cells. Here, we review the mechanism of action of these non‐lymphoid regulatory cells as they relate to the induction or maintenance of tolerance in organ transplantation.     

Induction of T helper 3 regulatory cells by dendritic cells infected with porcine reproductive and respiratory syndrome virus

Delayed development of virus-specific immune response has been observed in pigs infected with the porcine reproductive and respiratory syndrome virus (PRRSV). Several studies support the hypothesis that the PRRSV is capable of modulating porcine immune system, but the mechanisms involved are yet to be defined. In this study, we evaluated the induction of T regulatory cells by PRRSV-infected dendritic cells (DCs). Our results showed that PRRSV-infected DCs significantly increased Foxp3⁺CD25⁺ T cells, an effect that was reversible by IFN-α treatment, and this outcome was reproducible using two distinct PRRSV strains. Analysis of the expressed cytokines suggested that the induction of Foxp3⁺CD25⁺ T cells is dependent on TGF-β but not IL-10. In addition, a significant up-regulation of Foxp3 mRNA, but not TBX21 or GATA3, was detected. Importantly, our results showed that the induced Foxp3⁺CD25⁺ T cells were able to suppress the proliferation of PHA-stimulated PBMCs. The T cells induced by the PRRSV-infected DCs fit the Foxp3⁺CD25⁺ T helper 3 (Th3) regulatory cell phenotype described in the literature. The induction of this cell phenotype depended, at least in part, on PRRSV viability because IFN-α treatment or virus inactivation reversed these effects. In conclusion, this data supports the hypothesis that the PRRSV succeeds to establish and replicate in porcine cells early post-infection, in part, by inducing Th3 regulatory cells as a mechanism of modulating the porcine immune system.