树突状细胞与免疫耐受的研究进展

ＤＣ参与胸腺Ｔ细胞的阴性选择过程，也参与外周Ｔ细胞的致耐，ＤＣ可能是唯一具有胸腺Ｔ细胞阴性选择功能的细胞，在外周，ＤＣ通过“否决”效应，诱导Ｔ细胞失能及其他一些机制诱导耐受生成，本文就此方面研究予以综述。     

浆细胞样树突状细胞与免疫耐受

浆细胞样树突状细胞(PDC)来源于淋巴系干细胞,其表面标志、功能有别于髓系DC,不仅在抗病毒免疫中发挥重要作用,而且通过多种途径诱导T细胞失能和调节性T细胞的形成,从而参与免疫耐受的诱导.PDC诱导T细胞免疫耐受的分子机制与吲哚胺2,3-双加氧酶(IDO)-色氨酸代谢通路和具有抑制功能的膜分子密切相关.深入阐明PDC诱导耐受的机制,将为免疫耐受异常相关的疾病的治疗提供新方案.     

树突状细胞诱导外周免疫耐受的机制

树突状细胞既能启动免疫应答 ,又能诱导免疫耐受。目前对树突状细胞诱导外周耐受方面的研究进展迅速 ,本文就未成熟树突状细胞、免疫抑制因子处理的树突状细胞及转基因树突状细胞在诱导外周免疫耐受中的作用作一综述 ,这可能是治疗自身免疫性疾病和移植排斥反应的新途径     

调节性Ｔ细胞与免疫耐受

近年来关于调节Ｔ细胞在移植模型中介导免疫耐受的作用有相当大的进展,免疫调节的机制特别在感染性耐受途径中是通过调节性Ｔ细胞,包括Ｔh2细胞因子（ＩＬ－４、ＩＬ－１０和ＴＧＦ－β）均起着直接或间接的促进作用。胸腺是促进调节性Ｔ细胞产生的微环境,自身免疫性疾病模型中,调节性细胞有不同的胸腺来源的Ｔ细胞亚群,ＣＤ4^ T细胞和CD8^ T细胞都可调节免疫反应,诱导移植免疫耐受。     

树突状细胞和免疫耐受

树突状细胞（DC）是职业抗原递呈细胞，即可触发排斥反应，又能够调节T细胞反应而产生外周免疫耐受。尽管其诱导外周免疫耐受的确切机制尚不清楚，但DC在诱导供体特异性T无反应细胞（Treg）凋亡，供体特异T调整细胞，转基因诱导耐受DC以及T辅助细胞转化方向等方面都取得了明显进展。进一步研究DC在诱导自身抗原耐受的作用机理，可以揭示DC诱导移植免疫耐受，以实现人类在不依赖免疫抑制剂的条件下产生供体特异性免疫耐受，本文拟就有关内容作一综述。     

调节性免疫细胞在诱导移植免疫耐受中的作用

目前,器官移植是许多重大疾病根治的惟一手段,如尿毒症、重症肝衰竭、白血病等。但是器官移植最大的问题是移植排斥反应。现在,临床上防止移植排斥最常用的策略是终生使用免疫抑制剂。但使用免疫抑制剂会出现许多并发症,如机会性感染、发生肿瘤、影响儿童生长发育等,还会给患者     

树突状细胞与移植免疫耐受研究进展

诱导供者特异性免疫耐受是最终克服移植排斥提高受者生存质量的有效途径之一。近年随着对树突状细胞发育成熟过程的认识步步深入，树突状细胞在移植排斥和移植耐受平衡中的双向调节作用引入注目。     

抑制性树突状细胞诱导移植免疫耐受的研究进展

树突状细胞（DC）是功能强大的专职抗原呈递细胞。在器官或细胞移植中，DC通过直接或间接识别途径呈递抗原活化T细胞，引起移植免疫排斥反应，但某些特殊类型的DC也可以产生抑制免疫应答，促进免疫耐受的作用。基于DC这种生物学特性的异质性，目前有多种生物学策略诱生抑制性DC诱导移植免疫耐受。     

基因修饰树突状细胞诱导移植免疫耐受研究进展

在移植免疫反应中 ,树突状细胞 (DC)作为专职抗原提呈细胞 ,既可活化T、B细胞生产免疫应答 ,同时某些类型DC由于缺乏共刺激分子或表达某些抑制性细胞因子而能诱导移植免疫耐受。针对DC提呈抗原及活化T、B细胞的多个环节 ,目前有许多策略将不同目的基因转染不同来源的DC ,让其表达不同的表面分子或分泌免疫抑制因子 ,以诱导移植免疫耐受     

IL-2在免疫耐受中的作用

IL-2是一种具有多种生物学功能的细胞因子,它通过增强T淋巴细胞功能而促进器官移植后免疫排斥反应的发生发展.但新近研究表明IL-2还在维持机体稳定状态、延长移植物存活、以及诱导和维持免疫耐受中起着重要作用.     

Programmed cell death of dendritic cells in immune regulation

Summary: Programmed cell death is essential for the maintenance of lymphocyte homeostasis and immune tolerance. Dendritic cells (DCs), the most efficient antigen-presenting cells, represent a small cell population in the immune system. However, DCs play major roles in the regulation of both innate and adaptive immune responses. Programmed cell death in DCs is essential for regulating DC homeostasis and consequently, the scope of immune responses. Interestingly, different DC subsets show varied turnover rates in vivo. The conventional DCs are relatively short-lived in most lymphoid organs, while plasmacytoid DCs are long-lived cells. Mitochondrion-dependent programmed cell death plays an important role in regulating spontaneous DC turnover. Antigen-specific T cells are also capable of killing DCs, thereby providing a mechanism for negative feedback regulation of immune responses. It has been shown that a surplus of DCs due to defects in programmed cell death leads to overactivation of lymphocytes and the onset of autoimmunity. Studying programmed cell death in DCs will shed light on the roles for DC turnover in the regulation of the duration and magnitude of immune responses in vivo and in the maintenance of immune tolerance.     

Immune privilege induced by regulatory T cells in transplantation tolerance

Summary:  Immune privilege was originally believed to be associated with particular organs, such as the testes, brain, the anterior chamber of the eye, and the placenta, which need to be protected from any excessive inflammatory activity. It is now becoming clear, however, that immune privilege can be acquired locally in many different tissues in response to inflammation, but particularly due to the action of regulatory T cells (Tregs) induced by the deliberate therapeutic manipulation of the immune system toward tolerance. In this review, we consider the interplay between Tregs, dendritic cells, and the graft itself and the resulting local protective mechanisms that are coordinated to maintain the tolerant state. We discuss how both anti-inflammatory cytokines and negative costimulatory interactions can elicit a number of interrelated mechanisms to regulate both T-cell and antigen-presenting cell activity, for example, by catabolism of the amino acids tryptophan and arginine and the induction of hemoxygenase and carbon monoxide. The induction of local immune privilege has implications for the design of therapeutic regimens and the monitoring of the tolerant status of patients being weaned off immunosuppression.     

Mechanisms of peripheral tolerance to allergens

The immune system is regulated to protect the host from exaggerated stimulatory signals establishing a state of tolerance in healthy individuals. The disequilibrium in immune regulatory vs effector mechanisms results in allergic or autoimmune disorders in genetically predisposed subjects under certain environmental conditions. As demonstrated in allergen‐specific immunotherapy and in the healthy immune response to high‐dose allergen exposure models in humans, T regulatory cells are essential in the suppression of Th2‐mediated inflammation, maintenance of immune tolerance, induction of the two suppressive cytokines interleukin‐10 and transforming growth factor‐β, inhibition of allergen‐specific IgE, and enhancement of IgG4 and IgA. Also, suppression of dendritic cells, mast cells, and eosinophils contributes to the construction of peripheral tolerance to allergens. This review focuses on mechanisms of peripheral tolerance to allergens with special emphasis on recent developments in the area of immune regulation.     

Intranasal peptide‐induced tolerance and linked suppression: consequences of complement deficiency

A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B‐cell and T‐cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild‐type C57BL/6 and C1q‐, C3‐, C4‐ and C5‐deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3‐deficient mice failed to generate a functional regulatory T (Treg) –dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3‐deficient DC to up‐regulate the arginine‐consuming enzyme, inducible nitric oxide synthase (Nos‐2), in the presence of antigen‐specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide‐mediated induction of tolerance to HY by modulating DC function.     

Antigen-presenting cells and tolerance induction

T cell tolerance induction to foreign and self-antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though new methods became available to investigate immunoregulatory mechanisms. Antigen-presenting cells play a pivotal role in transferring information from the periphery of the organism to lymphoid organs. There, they initiate not only the activation of naive T cells but seem to deliver important signals which result in T cell unresponsiveness with antigen-specific tolerance induction.     

Dendritic cells,T cell tolerance and therapy of adverse immune reactions

Dendritic cells (DC) are uniquely able to either induce immune responses or to maintain the state of self tolerance. Recent evidence has shown that the ability of DC to induce tolerance in the steady state is critical to the prevention of the autoimmune response. Likewise, DC have been shown to induce several type of regulatory T cells including Th2, Tr1, Ts and NKT cells, depending on the maturation state of the DC and the local microenvironment. DC have been shown to have therapeutic value in models of allograft rejection and autoimmunity, although no success has been reported in allergy. Several strategies, including the use of specific DC subsets, genetic modification of DC and the use of DC at various maturation stages for the treatment of allograft rejection and autoimmune disease are discussed. The challenge for the future use of DC therapy in human disease is to identify the appropriate DC for the proposed therapy; a task made more daunting by the extreme plasticity of DC that has recently been demonstrated. However, the progress achieved to date suggests that these are not insurmountable obstacles and that DC may become a useful therapeutic tool in transplantation and autoimmune disease.