人胃癌肿瘤浸润树突状细胞的形态学观察

目的　探讨人胃癌肿瘤浸润树突状细胞 (TIDC)的形态学特征。方法　应用免疫组织化学、光镜和电镜的方法观察人胃癌TIDC的分布和形态学变化。结果　TIDC主要分布癌周区 ,病变早期TIDC比病变晚期数量 (P <0 0 1)。电镜下 ,TIDC体积较大 ,形态不规则 ,表面有许多树突状突起 ,细胞核不规则 ,可见核仁 ,胞质内有丰富的线粒体、核糖体、高尔基复合体和内质网。TIDC与肿瘤浸润淋巴细胞 (TIL)和肿瘤接触方式和形式上呈多样性 ,一对一 ,一对多 ,或形成簇的接触方式 ,有紧密膜接触、指状膜接触和球状膜接触形式。结论　本实验提示TIDC数量多少与肿瘤的进展有关 ,TIDC与肿瘤浸润淋巴细胞和肿瘤细胞之间关系密切。     

树突状细胞在人类肾炎肾组织中的分布特点及临床意义

目的 研究树突状细胞在人类肾炎肾组织中的分布、特点及临床意义。方法 选择经肾活检和临床资料确诊的不同类型肾炎患者133例。采用免疫荧光双标记染色与低照度荧光显微镜图像分析检测方法，观察树突状细胞在肾炎患者肾组织中分布与改变。结果肾炎患者肾组织中树突状细胞分布的面积、数量及密度均明显增多。从分布特点来看，树突状细胞主要分布于肾小管、肾间质和肾血管，而肾小球基本未见分布。此外，树突状细胞在肾小管间质分布程度随肾炎肾小管间质病变程度加重而明显增加。结论树突状细胞可能参与了肾脏疾病的免疫病理机制，并与肾小管间质病变密切相关。     

基于打破树突状细胞耐受的抗肿瘤免疫治疗

树突状细胞(DC)是专职抗原呈递细胞,具有强大的免疫监视功能.由于在诱导免疫反应中的重要作用,DC已被广泛地应用于抗肿瘤免疫治疗.但是由于肿瘤细胞对荷瘤宿主免疫系统,尤其是对DC功能的抑制,使以DC为基础的抗肿瘤免疫治疗疗效受到了很大的限制.所以,通过调节DC功能,可打破肿瘤对DC的免疫抑制,引导有效的抗肿瘤反应,提高以DC为基础的抗肿瘤免疫效果,这在抗肿瘤免疫治疗中具有重要意义.     

人外周血树状突细胞在体外对LAK杀伤活性的影响

本文采用三因素不同水平的析因设计，研究了人外周血树状突细胞在体外对ＬＡＫ抗肿瘤作用的影响。结果显示，３种浓度的树状突细胞均能增强ＬＡＫ的杀伤活性（Ｐ＜０．００１），以中等浓度的树状突细胞作用最为明显。加入ＩＬ－２后，树状突细胞对ＬＡＫ抗肿瘤活性的增强程度进一步提高。     

PPD Extract Induces the Maturation of Human Monocyte-Derived Dendritic Cells

Dendritic cells (DCs) are the most powerful antigen presenting cells, capable of inducing T-dependent immune responses even in naive T cells. DCs are of special interest as cellular adjuvants for immunity induction in clinical settings and several methods for their generation and maturation are recently under investigation. The present study was set out to define the effects of PPD (Purified Protein Derivative), a mycobacterial extract used in the tuberculin skin test, on in vitro differentiation and maturation of human monocyte derived dendritic cells. Immature DCs were prepared from the peripheral blood monocytes of healthy volunteers by culturing in a medium supplemented with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). The resultant cells were then stimulated with PPD extract and their properties such as cell morphology and the expression of key surface molecules were compared with tumor necrosis factor-α (TNF-α) stimulated immature DCs. Our results suggest that mycobacterial purified extract is as potent as TNF-α, a well-established DC stimulator, in induction of maturation in human monocyte derived DCs. We also ruled out the contribution of lipopolysaccharide (LPS) and beta-glucan contamination in maturation effect of PPD preparations. So, PPD as an examined safe material for in vivo consumption could be used to stimulate DC maturation in DC based immunotherapy protocols.     

树突状细胞在多发性骨髓瘤免疫治疗中的应用进展

多发性骨髓瘤(multiple myeloma,MM)患者在常规治疗达完全缓解后,体内仍会存在微小残留病变(minimal residual disease,MRD),而成为复发的根源,此时依靠机体有效的抗肿瘤免疫反应是消除MRD的一个有效的方法。树突状细胞(dendritic cell,DC)是目前功能最强大、唯一能激活初始型T细胞的抗原递呈细胞(antigen presenting cell,APC),能有效的把MM的肿瘤抗原呈递给T细胞,产生特异性CTL而达到杀灭肿瘤细胞的目的。对DC在MM免疫治疗中的基础研究和临床应用进展的研究很有意义。     

人体上呼吸道内气溶胶沉积的实验研究

研究人体呼吸道内气溶胶沉积规律,对于认识有毒气溶胶对人体健康的影响和提高治疗药物气溶胶的治疗效果具有重要意义.采用激光快速成型技术制作人体上呼吸道的实验模型,在呼吸流量为30 L/min的状态下,分别对粒径为0.3和6.5 μm的气溶胶在人体上呼吸道内的沉积进行实验研究,分析气溶胶在上呼吸道内的沉积规律.研究结果表明;气溶胶在咽、喉和气管位置存留较多;气溶胶粒径对其在上呼吸道内的沉积模式影响较小,两种粒径气溶胶的沉积模式很相似,仅对其在呼吸道内不同部位的沉积率影响较大;惯性碰撞和湍流扩散是气溶胶的主要沉积机制,气溶胶在人体呼吸道内不同部位的沉积率均随惯性参数值的增加而升高.     

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。     

Cytokine-Producing Dendritic Cells in the Pathogenesis of Inflammatory Skin Diseases

Introduction  Inflammatory skin diseases can be examined from many viewpoints. In this review, we consider three distinct cutaneous inflammatory diseases from the point of view of their major lesional dendritic cell (DC) subpopulations. The DC populations considered are Langerhans cells, myeloid DCs, and plasmacytoid DCs (pDCs), with specific attention to the presence and role of the inflammatory counterparts of these cells. From such a “dendritic cell-centric” focus, psoriasis, atopic dermatitis (AD), and cutaneous lupus erythematosus (CLE) are explored. Discussion  In psoriasis, there is a specific population of myeloid “inflammatory” DCs that appears to play an important pathogenic role, while pDCs have been recently implicated in the initiation of psoriatic lesions. In AD, Langerhans cells may be important during initiation, while “inflammatory dendritic epidermal cells” (IDECs) appear to be abundant in lesional epidermis and dermis and contribute to maintenance of AD. These IDECs may actually be analogous to the myeloid inflammatory DCs found in the epidermal and dermal compartments of the skin in psoriasis, although they express distinct surface markers and induce different T cell polarities as a result of different cytokine milieu in which they develop. CLE has been recently characterized as a type I IFN-mediated disease, and pDCs are integral to the pathogenesis of this disease. Conclusion  Thus, these DC subpopulations and their products will be reviewed in the context of these three cutaneous diseases to provide clinico-pathophysiological correlations between the lesional DCs, their products, and the skin diseases.     

血管活性肠肽对树突状细胞免疫调节作用研究进展

神经系统与免疫系统通过神经肽、神经递质和细胞因子相互作用。血管活性肠肽(VIP)作为一种重要的神经肽参与炎症反应和免疫应答的调控。近年研究表明VIP能通过与树突状细胞(DC)表面的受体结合调节DC的表型和功能成熟,在DC体内迁移和功能成熟中发挥重要作用。VIP主要通过调节DC膜表面黏附分子和共刺激分子的表达、趋化因子及其受体的表达和趋化活性,诱导Th细胞分化以及抗原提呈功能发挥作用。     

Dendritic Cells in the Context of Human Tumors: Biology and Experimental Tools

Dendritic cells (DC) are the most potent and versatile antigen-presenting cells (APC) in the immune system. DC have an exceptional ability to comprehend the immune context of a captured antigen based on molecular signals identified from its vicinity. The analyzed information is then conveyed to other immune effector cells. Such capability enables DC to play a pivotal role in mediating either an immunogenic response or immune tolerance towards an acquired antigen. This review summarizes current knowledge on DC in the context of human tumors. It covers the basics of human DC biology, elaborating on the different markers, morphology and function of the different subsets of human DC. Human blood-borne DC are comprised of at least three subsets consisting of one plasmacytoid DC (pDC) and two to three myeloid DC (mDC) subsets. Some tissues have unique DC. Each subset has a different phenotype and function and may induce pro-tumoral or anti-tumoral effects. The review also discusses two methods fundamental to the research of DC on the single-cell level: multicolor flow cytometry (FCM) and image-based cytometry (IC). These methods, along with new genomics and proteomics tools, can provide high-resolution information on specific DC subsets and on immune and tumor cells with which they interact. The different layers of collected biological data may then be integrated using Immune-Cytomics modeling approaches. Such novel integrated approaches may help unravel the complex network of cellular interactions that DC carry out within tumors, and may help harness this complex immunological information into the development of more effective treatments for cancer.     

树突状细胞在人皮肤黑色素瘤组织中抗原提呈效应的形态学观察

目的探讨人皮肤黑色素瘤组织中肿瘤浸润树突状细胞（TIDC）的抗肿瘤效应。方法采用光镜、透射电镜和免疫组化方法观察19例手术切除的人皮肤黑色素瘤中TIDC和肿瘤浸润淋巴细胞（TIL）抗肿瘤效应的形态学表现。结果早期人皮肤黑色素瘤组织中的类高内皮微静脉和淋巴管内、外均可见大量淋巴细胞和树突状细胞集聚和迁移;病变早期TIDC和TIL浸润比晚期明显（P〈0．01）。透射电镜下,TIDC大致有两种形态。一种TIDC体积大,表面有许多树枝状突起,核不规则,胞浆内有丰富的细胞器;另一种TIDC突起较少,细胞器也较少。TIDC与肿瘤细胞、TIDC与TIL、TIL与TIL、TIL与肿瘤细胞之间存在多种形式的膜接触。与TIL接触的肿瘤细胞呈凋亡状态。晚期病变组织中TIDC与TIL数量明显减少,于癌巢内常见凋亡的TIDC与TIL。结论人皮肤黑色素瘤组织中存在不同形态的TIDC与TIL,并通过类高内皮微静脉和淋巴管迁移;TIDC、TIL、癌细胞彼此密切作用,在肿瘤局部即可发生抗肿瘤免疫应答反应,反应程度与肿瘤进展呈负相关。     

奶牛乳腺肥大细胞的粘膜免疫学特征

应用改良甲苯胺蓝染色法 (MTB )和阿尔辛蓝 番红鉴别染色法 (AB S )对静止期和活动期奶牛乳腺肥大细胞的粘膜免疫学性质进行了研究。MTB染色结果显示 ,静止期乳腺中的肥大细胞主要分布于各级输乳管上皮基膜区 ,小血管周围也有肥大细胞分布。在活动期 ,肥大细胞主要分布于腺泡上皮基膜附近 ,上皮内也有极少数肥大细胞分布 ,小叶间结缔组织中的肥大细胞则分布于小叶间导管或输乳管上皮基膜区。AB S染色证实 ,乳腺肥大细胞只被阿尔辛蓝染成蓝色 ,而不被结缔组织型肥大细胞的标志性染料番红着染。这表明 ,乳腺肥大细胞是一种典型的粘膜型肥大细胞 (MMC ) ,并参与构成乳腺粘膜免疫的第一道防线。     

Subset of Vascular Dendritic Cells Transforming into Foam Cells in Human Atherosclerotic Lesions

It has been previously demonstrated that S-100 positive vascular dendritic cells are involved in human atherosclerosis and they usually show a low level of accumulation of lipids in their cytoplasm, even though they located among foam cells and cellular debris in atherosclerotic lesions. During ongoing immunohistochemical investigations, however, we have found that a few S-100 positive cells exhibited a foam cell appearance. Therefore, we undertook an electronmicroscopic examination to see if any foam cells exhibit the distinctive features of vascular dendritic cells such as the presence of dense granules and a tubulovesicular system uniquely found in well differentiated dendritic cells. Foam cells exhibiting the typical characteristics of vascular dendritic cells were indeed found. Their cytoplasm contained a large number of lipid vacuoles and cisterns of the tubulovesicular system as well as dense granules which, in contrast to lysosomes present in macrophages, did not transform into phagolysosomes. The formation of a central lamina inside cisterns of the tubulovesicular system was also detected. These pentalaminal structures, comprised of two parallel limiting membranes and a central lamina, are similar to the Birbeck granules present in human epidermal Langerhans cells. From our present observations we speculate that the defense mechanisms against extensive lipid accumulation may be broken in some vascular dendritic cells, causing them to transform into foam cells.     

Development of Immunogenic Tumor-Loaded Dendritic Cells Through Physical Perturbation and Apoptotic Cell Loading

To improve understanding of the forces that drive monocytes to transition into dendritic cells (), we developed an experimental system that converts monocytes to DC by passage of leukocytes through a 400 μm silica bead column. The results demonstrate that overnight culture of column-treated monocytes causes a phenotypic conversion that is characteristically displayed by immature DC. These phenotypic changes were enhanced when the DC were loaded with apoptotic cells, leading to increased expression of the DC maturation-associated markers CD83, CD80 and the chemokine receptor CCR7. The DC demonstrated potent induction of allogeneic T cell proliferation and the capacity to activate autologous CD8⁺ T cells. The CD8 T cells expressed augmented levels of perforin, IFN-γ and TNF-α and mediated CTCL cell apoptosis. These studies demonstrate that physical contact with silica beads combined with loading of apoptotic tumor cells induces synchronized, rapid conversion of human monocytes to DC, which can efficiently stimulate CD8⁺ T cells. These results may aid in the development of more efficient DC vaccines that can be loaded with the universe of antigens available in apoptotic tumor cells in a rapid, clinically practical fashion.     

树突状细胞在榄香烯复合瘤苗主动免疫效应中的作用

本实验以HCa F或L6 1 5榄香烯复合瘤苗 (H TCV或L TCV )、H TCV溶解物 (TH )、短小棒状菌 (CP )免疫小鼠 ,分离制备其脾脏DC ,在体外分别用相应瘤细胞溶解物 (H或L )和瘤苗溶解物 (TH或TL )冲激后 ,以MTT法检测其诱导同系小鼠脾不粘附细胞增殖的能力。结果表明用榄香烯复合瘤苗或其溶解物免疫DC供鼠和体外冲激DC ,可增强其诱导同系小鼠脾不粘附细胞增殖的作用 ,给DC供鼠注射CP可进一步增强DC的这一作用     

Mucosal Immunity in the Human Female Reproductive Tract: Cytotoxic T Lymphocyte Function in the Cervix and Vagina of Premenopausal and Postmenopausal Women

PROBLEM: To investigate the mucosal immune system in the cervix and vagina of premenopausal women in terms of immune cells present and cytolytic capacity of mucosal CD3+ T cells in the lower reproductive tract. METHODS: Fresh tissue fragments prepared by vibratome sectioning were analyzed for the presence of immune cells by confocal scanning laser microscopy (CSLM). Isolated reproductive tract cells prepared by enzymatic digestion were analyzed for CD3+ T cell phenotype by FACS analysis and for cytolytic function by an anti-CD3 mAb mediated redirected lysis assay. RESULTS: As determined by CSLM, CD3+ cells as well as macrophages and dendritic cells are distributed throughout the lower female reproductive tract in both the epithelium and subepithelial mucosa. It was found that cervical and vaginal tissues from pre- and post-menopausal women contain CD3+ T cells (CTL) that have cytolytic activity, when measured in an antigen non-specific anti-CD3 mAb mediated redirected lysis assay. CONCLUSIONS: These results indicate that the lower reproductive tract of women is immuno-competent as judged by the presence of CD3, CD4, CD8, macrophage, and dendritic cells in the endocervix, ectocervix, and vagina of premenopausal and postmenopausal women. Further, these studies demonstrate that CD3+ T cells with cytolytic activity are present in the cervix and vagina during the proliferative and secretory phases of the menstrual cycle and following menopause.     

The Role of Plasmacytoid and Myeloid Dendritic Cells in Induction of Asthma in a Mouse Model and the Effect of a TLR9 Agonist on Dendritic Cells

Purpose

To determine the role of plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) in priming effector T cells to induce allergy, and to evaluate the effect of immunostimulatory sequences (ISS, TLR9 agonist) on dendritic cells.

Methods

Cultured mDC and pDC with/without ISS were injected intratracheally into sensitized Balb/C mice. Mice were sacrificed, and then pulmonary function tests, bronchoalveolar lavage (BAL), cell counts, and cytokine levels were evaluated. Migration of dendritic cells was also evaluated after ISS administration.

Results

In mice injected with mDC, airway hyperresponsiveness, eosinophil counts, and Th2 cytokine levels in BAL increased with increasing numbers of mDC injected. However, in mice injected with pDC, none of these changed, suggesting poor priming of T cells by pDC. In addition, mDC pulsed with ISS inhibited asthmatic reactions, and ISS administration inhibited migration of DC to the lung.

Conclusions

We suggest that pDC played a limited role in priming T cells in this asthma model and that mDC played a major role in inducing asthma. In addition, ISS inhibited migration of DC to the lung.     

ILT及IDO在树突状细胞介导免疫耐受中的作用及机制

树突状细胞在诱导机体免疫耐受中发挥重要的作用。它可调节其表面免疫球蛋白样转录物3和免疫球蛋白样转录物4的表达,抑制T细胞的活化,并形成“抑制性T细胞级联”,还可上调吲哚胺2,3双加氧酶的表达,通过耗竭局部环境中色氨酸抑制T细胞功能。对树突状细胞诱导免疫耐受机制的研究在自身免疫性疾病、慢性感染性疾病、肿瘤和移植排斥反应的防治方面都具有非常重要的意义。     

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles

Mucosal immune responses are the first‐line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non‐invasiveness; (iii) high‐patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production.