Divergent Effects of Dendritic Cells on Pancreatitis

Science.gov (United States)

2015-09-01

role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller

Intratracheal administration of fullerene nanoparticles activates splenic CD11b+ cells

International Nuclear Information System (INIS)

Ding, Ning; Kunugita, Naoki; Ichinose, Takamichi; Song, Yuan; Yokoyama, Mitsuru; Arashidani, Keiichi; Yoshida, Yasuhiro

2011-01-01

Highlights: → Fullerene administration triggered splenic responses. → Splenic responses occurred at different time-points than in the lung tissue. → CD11b + cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-α. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-κB and NFAT in splenocytes at 6 days post-administration. Finally, CD11b + cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

Splenic littoral cell angioma. Radio pathological correlation in two cases

International Nuclear Information System (INIS)

Asensio, J.; Montero, N.; Perez-Cidoncha, P.

2000-01-01

We present two cases of Littoral Cell Angiomas (LCA), a recently described variant of splenic angioma which originates in the cells that line the sinusoids from the red pulp (littoral cell). The histopathological and immunohistochemical characteristics of this neoplasm verifies its origin in the littoral cell with an intermediate origin between the endothelial and histiocyte cell and makes it possible to consider it as a pathological entity which is differentiated from the hemangiomas. The imaging findings are indistinguishable from the other splenic vascular neoplasms and the role of the Magnetic Resonance (MRI) stands out. (Author) 21 refs

Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

NARCIS (Netherlands)

van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

2005-01-01

Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity.

Science.gov (United States)

Westerterp, Marit; Gautier, Emmanuel L; Ganda, Anjali; Molusky, Matthew M; Wang, Wei; Fotakis, Panagiotis; Wang, Nan; Randolph, Gwendalyn J; D'Agati, Vivette D; Yvan-Charvet, Laurent; Tall, Alan R

2017-06-06

Autoimmune diseases such as systemic lupus erythematosus (SLE) are associated with increased cardiovascular disease and reduced plasma high-density lipoprotein (HDL) levels. HDL mediates cholesterol efflux from immune cells via the ATP binding cassette transporters A1 and G1 (ABCA1/G1). The significance of impaired cholesterol efflux pathways in autoimmunity is unknown. We observed that Abca1/g1-deficient mice develop enlarged lymph nodes (LNs) and glomerulonephritis suggestive of SLE. This lupus-like phenotype was recapitulated in mice with knockouts of Abca1/g1 in dendritic cells (DCs), but not in macrophages or T cells. DC-Abca1/g1 deficiency increased LN and splenic CD11b + DCs, which displayed cholesterol accumulation and inflammasome activation, increased cell surface levels of the granulocyte macrophage-colony stimulating factor receptor, and enhanced inflammatory cytokine secretion. Consequently, DC-Abca1/g1 deficiency enhanced T cell activation and T h 1 and T h 17 cell polarization. Nlrp3 inflammasome deficiency diminished the enlarged LNs and enhanced T h 1 cell polarization. These findings identify an essential role of DC cholesterol efflux pathways in maintaining immune tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells.

Science.gov (United States)

Morelli, Adrian E; Thomson, Angus W

2014-08-01

Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function. Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients. We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.

Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1.

Science.gov (United States)

Sirvent, Sofía; Soria, Irene; Cirauqui, Cristina; Cases, Bárbara; Manzano, Ana I; Diez-Rivero, Carmen M; Reche, Pedro A; López-Relaño, Juan; Martínez-Naves, Eduardo; Cañada, F Javier; Jiménez-Barbero, Jesús; Subiza, Javier; Casanovas, Miguel; Fernández-Caldas, Enrique; Subiza, José Luis; Palomares, Oscar

2016-08-01

Allergen immunotherapy (AIT) is the only curative treatment for allergy. AIT faces pitfalls related to efficacy, security, duration, and patient compliance. Novel vaccines overcoming such inconveniences are in demand. We sought to study the immunologic mechanisms of action for novel vaccines targeting dendritic cells (DCs) generated by coupling glutaraldehyde-polymerized grass pollen allergoids to nonoxidized mannan (PM) compared with glutaraldehyde-polymerized allergoids (P) or native grass pollen extracts (N). Skin prick tests and basophil activation tests with N, P, or PM were performed in patients with grass pollen allergy. IgE-blocking experiments, flow cytometry, confocal microscopy, cocultures, suppression assays, real-time quantitative PCR, ELISAs, and ELISpot assays were performed to assess allergen capture by human DCs and T-cell responses. BALB/c mice were immunized with PM, N, or P. Antibody levels, cytokine production by splenocytes, and splenic forkhead box P3 (FOXP3)(+) regulatory T (Treg) cells were quantified. Experiments with oxidized PM were also performed. PM displays in vivo hypoallergenicity, induces potent blocking antibodies, and is captured by human DCs much more efficiently than N or P by mechanisms depending on mannose receptor- and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated internalization. PM endorses human DCs to generate functional FOXP3(+) Treg cells through programmed death ligand 1. Immunization of mice with PM induces a shift to nonallergic responses and increases the frequency of splenic FOXP3(+) Treg cells. Mild oxidation impairs these effects in human subjects and mice, demonstrating the essential role of preserving the carbohydrate structure of mannan. Allergoids conjugated to nonoxidized mannan represent suitable vaccines for AIT. Our findings might also be of the utmost relevance to development of therapeutic interventions in other immune tolerance-related diseases. Copyright �

Immune monitoring using mRNA-transfected dendritic cells

DEFF Research Database (Denmark)

Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

2016-01-01

Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

Neutrophils, dendritic cells and Toxoplasma.

Science.gov (United States)

Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

2004-03-09

Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

Intratracheal administration of fullerene nanoparticles activates splenic CD11b{sup +} cells

Energy Technology Data Exchange (ETDEWEB)

Ding, Ning [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Kunugita, Naoki [Department of Environmental Health, National Institute of Public Health, 2-3-6, Minami, Wako 351-0197 (Japan); Ichinose, Takamichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201 (Japan); Song, Yuan [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yokoyama, Mitsuru [Bio-information Research Center, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Arashidani, Keiichi [School of Health Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan); Yoshida, Yasuhiro, E-mail: freude@med.uoeh-u.ac.jp [Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555 (Japan)

2011-10-30

Highlights: {yields} Fullerene administration triggered splenic responses. {yields} Splenic responses occurred at different time-points than in the lung tissue. {yields} CD11b{sup +} cells were demonstrated to function as responder cells to fullerene. - Abstract: Fullerene nanoparticles ('Fullerenes'), which are now widely used materials in daily life, have been demonstrated to induce elevated pulmonary inflammation in several animal models; however, the effects of fullerenes on the immune system are not fully understood. In the present study, mice received fullerenes intratracheally and were sacrificed at days 1, 6 and 42. Mice that received fullerenes exhibited increased proliferation of splenocytes and increased splenic production of IL-2 and TNF-{alpha}. Changes in the spleen in response to fullerene treatment occurred at different time-points than in the lung tissue. Furthermore, fullerenes induced CDK2 expression and activated NF-{kappa}B and NFAT in splenocytes at 6 days post-administration. Finally, CD11b{sup +} cells were demonstrated to function as responder cells to fullerene administration in the splenic inflammatory process. Taken together, in addition to the effects on pulmonary responses, fullerenes also modulate the immune system.

Dendritic excitability modulates dendritic information processing in a purkinje cell model.

Science.gov (United States)

Coop, Allan D; Cornelis, Hugo; Santamaria, Fidel

2010-01-01

Using an electrophysiological compartmental model of a Purkinje cell we quantified the contribution of individual active dendritic currents to processing of synaptic activity from granule cells. We used mutual information as a measure to quantify the information from the total excitatory input current (I(Glu)) encoded in each dendritic current. In this context, each active current was considered an information channel. Our analyses showed that most of the information was encoded by the calcium (I(CaP)) and calcium activated potassium (I(Kc)) currents. Mutual information between I(Glu) and I(CaP) and I(Kc) was sensitive to different levels of excitatory and inhibitory synaptic activity that, at the same time, resulted in the same firing rate at the soma. Since dendritic excitability could be a mechanism to regulate information processing in neurons we quantified the changes in mutual information between I(Glu) and all Purkinje cell currents as a function of the density of dendritic Ca (g(CaP)) and Kca (g(Kc)) conductances. We extended our analysis to determine the window of temporal integration of I(Glu) by I(CaP) and I(Kc) as a function of channel density and synaptic activity. The window of information integration has a stronger dependence on increasing values of g(Kc) than on g(CaP), but at high levels of synaptic stimulation information integration is reduced to a few milliseconds. Overall, our results show that different dendritic conductances differentially encode synaptic activity and that dendritic excitability and the level of synaptic activity regulate the flow of information in dendrites.

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

Science.gov (United States)

Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

Science.gov (United States)

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

Science.gov (United States)

Howson, Lauren J; Morris, Katrina M; Kobayashi, Takumi; Tovar, Cesar; Kreiss, Alexandre; Papenfuss, Anthony T; Corcoran, Lynn; Belov, Katherine; Woods, Gregory M

2014-05-01

The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration. © 2014 The Authors. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology Published by Wiley Periodicals, Inc.

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

Directory of Open Access Journals (Sweden)

L.D. Loopuijt

2007-10-01

Full Text Available To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37 on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively. Three cells (4.5% were bistratified, having thick dendrites, and the others (95.5% were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40% and 2 groups with inner (50-100% stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.

Science.gov (United States)

Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

2016-11-15

Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. Currently, the gold standard protocol for generating dendritic cells from monocytes across various species relies upon a combination of GM-CSF and IL-4 added to cell culture medium which is supplemented with FBS. The aim of this study was to substitute FBS with heterologous horse serum. For this purpose, equine monocyte-derived dendritic cells (eqMoDC) were generated in the presence of horse serum or FBS and analysed for the effect on morphology, phenotype and immunological properties. Changes in the expression of phenotypic markers (CD14, CD86, CD206) were assessed during dendritic cell maturation by flow cytometry. To obtain a more complete picture of the eqMoDC differentiation and assess possible differences between FBS- and horse serum-driven cultures, a transcriptomic microarray analysis was performed. Lastly, immature eqMoDC were primed with a primary antigen (ovalbumin) or a recall antigen (tetanus toxoid) and, after maturation, were co-cultured with freshly isolated autologous CD5 + T lymphocytes to assess their T cell stimulatory capacity. The microarray analysis demonstrated that eqMoDC generated with horse serum were indistinguishable from those generated with FBS. However, eqMoDC incubated with horse serum-supplemented medium exhibited a more characteristic dendritic cell morphology during differentiation from monocytes. A significant increase in cell viability was also observed in eqMoDC cultured with horse serum. Furthermore, eqMoDC generated in the presence of horse serum

Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates.

Science.gov (United States)

Franken, Lars; Klein, Marika; Spasova, Marina; Elsukova, Anna; Wiedwald, Ulf; Welz, Meike; Knolle, Percy; Farle, Michael; Limmer, Andreas; Kurts, Christian

2015-08-11

A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen.

Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

Science.gov (United States)

Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

2010-06-01

Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.

Characterization of nonlymphoid cells in rat spleen, with special reference to strongly Ia-positive branched cells in T-cell areas

International Nuclear Information System (INIS)

Dijkstra, C.D.

1982-01-01

By use of a monoclonal antibody against Ia antigen in an immunoperoxidase method, strongly Ia-positive branched cells are found in the T-cell areas of the splenic white pulp of the rat. In order to further characterize these cells, enzyme histochemical characteristics, phagocytic capacity, and irradiation sensitivity have been studied. Evidence is presented that these strongly Ia-positive branched cells represent interdigitating cells. The influence of whole-body irradiation on interdigitating cells is discussed. Comparison with data from the literature on the in vitro dendritic cell isolated from spleen cell suspensions reveals many similarities between the described interdigitating cell in vivo and the dendritic cell in vitro

CD163 positive subsets of blood dendritic cells

DEFF Research Database (Denmark)

Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

2006-01-01

CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important...... for internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...

A Model of Dendritic Cell Therapy for Melanoma

Directory of Open Access Journals (Sweden)

Ami eRadunskaya

2013-03-01

Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

CT imaging of splenic sequestration in sickle cell disease

International Nuclear Information System (INIS)

Sheth, S.; Piomelli, S.; Ruzal-Shapiro, C.; Berdon, W.E.

2000-01-01

Pooling of blood in the spleen is a frequent occurrence in children with sickle cell diseases, particularly in the first few years of life, resulting in what is termed ''splenic sequestration crisis.'' The spectrum of severity in this syndrome is wide, ranging from mild splenomegaly to massive enlargement, circulatory collapse, and even death. The diagnosis is usually clinical, based on the enlargement of the spleen with a drop in hemoglobin level by >2 g/dl, and it is rare that imaging studies are ordered. However, in the patient who presents to the emergency department with non-specific findings of an acute abdomen, it is important to recognize the appearance of sequestration on imaging studies. We studied seven patients utilizing contrast-enhanced CT scans and found two distinct patterns - multiple, peripheral, non-enhancing low-density areas or large, diffuse areas of low density in the majority of the splenic tissue. Although radiological imaging is not always necessary to diagnose splenic sequestration, in those situations where this diagnosis is not immediately obvious, it makes an important clarifying contribution. (orig.)

Controlling T-Cell Activation with Synthetic Dendritic Cells Using the Multivalency Effect

NARCIS (Netherlands)

Hammink, R.; Mandal, S.; Eggermont, L.J.; Nooteboom, M.; Willems, P.H.G.M.; Tel, J.; Rowan, A.E.; Figdor, C.G.; Blank, K.G.

2017-01-01

Artificial antigen-presenting cells (aAPCs) have recently gained a lot of attention. They efficiently activate T cells and serve as powerful replacements for dendritic cells in cancer immunotherapy. Focusing on a specific class of polymer-based aAPCs, so-called synthetic dendritic cells (sDCs), we

Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

LENUS (Irish Health Repository)

Michielsen, Adriana J

2011-01-01

Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

Science.gov (United States)

Nottage, Kerri A; Ware, Russell E; Winter, Bryan; Smeltzer, Matthew; Wang, Winfred C; Hankins, Jane S; Dertinger, Stephen D; Shulkin, Barry; Aygun, Banu

2014-11-01

More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc(99) m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum

OpenAIRE

Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

2016-01-01

BACKGROUND: Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including hor...

Dendritic cell-tumor cell hybrids and immunotherapy

DEFF Research Database (Denmark)

Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

2011-01-01

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

Acute splenic sequestration in a pregnant woman with homozygous sickle-cell anemia.

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Maia, Carolina Bastos; Nomura, Roseli Mieko Yamamoto; Igai, Ana Maria Kondo; Fonseca, Guilherme Hencklain; Gualandro, Sandra Menosi; Zugaib, Marcelo

2013-01-01

Homozygous (SS) sickle-cell anemia complicated by acute splenic sequestration in adults is a rare event, and it has never been reported during pregnancy. A 25-year-old woman with homozygous (SS) sickle-cell disease was hospitalized at 32 weeks' of gestation presenting weakness, abdominal pain, fever and hemoglobin of 2.4 g/dl. Abnormal fetal heart rate was detected by means of cardiotocography, and 5 units of packed red cells were transfused. Cesarean was performed at 37 weeks. Both mother and baby were discharged in a good general condition. This case report demonstrates the importance of immediate blood transfusion for treatment of fetal distress in cases of splenic sequestration during pregnancy. This treatment is essential for avoiding maternal and fetal complications.

[Imiquimod combined with dendritic cell vaccine decreases Treg proportion and enhances anti-tumor responses in mice bearing melanoma].

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Ren, Shurong; Wang, Qiubo; Zhang, Yanli; Lu, Cuixiu; Li, Ping; Li, Yumei

2017-02-01

Objective To investigate the therapeutic effect of Toll-like receptor 7 (TLR7) agonist imiquimod combined with dendritic cell (DC)-based tumor vaccine on melanoma in mice and the potential mechanism. Methods Melanoma-bearing mouse models were established by subcutanous injection of B16-OVA cells into C57BL/6 mice. DCs were isolated from mouse bone marrow and propagated in culture medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant mouse interleukin-4 (rmIL-4). DC vaccine (OVA-DC) was prepared by overnight incubation of DCs added with chicken ovalbumin. C57BL/6 mice were separated into four groups which were treated with PBS, topical imiquimod application, OVA-DC intradermal injection and imiquimod plus OVA-DC, respectively. The tumor size was calculated by digital vernier caliper. Peripheral blood CD4 + FOXP3 + Tregs of the tumor-bearing mice was detected by flow cytometry. The cytotoxicity of splenic lymphocyte against B16-OVA was assessed in vitro by CCK-8 assay. Results Compared with the other three groups, B16-OVA-bearing mice treated with imiquimod plus DC vaccine had the smallest tumor volume. The percentage of CD4 + FOXP3 + Tregs decreased significantly in the combined treated mice. The combined treatment enhanced significantly cytotoxicity of splenic lymphocytes against B16-OVA cells. Conclusion Imiquimod combined with antigen-pulsed-DC vaccine could reduce CD4 + FOXP3 + Treg proportion and promote anti-tumor effect in mice with melanoma.

CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

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Pedersen, Anders E; Ronchese, Franca

2007-01-01

Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

Human intestinal dendritic cells as controllers of mucosal immunity

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David Bernardo

2013-06-01

Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia.

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Audia, Sylvain; Rossato, Marzia; Santegoets, Kim; Spijkers, Sanne; Wichers, Catharina; Bekker, Cornelis; Bloem, Andries; Boon, Louis; Flinsenberg, Thijs; Compeer, Ewoud; van den Broek, Theo; Facy, Olivier; Ortega-Deballon, Pablo; Berthier, Sabine; Leguy-Seguin, Vanessa; Martin, Laurent; Ciudad, Marion; Samson, Maxime; Trad, Malika; Lorcerie, Bernard; Janikashvili, Nona; Saas, Philippe; Bonnotte, Bernard; Radstake, Timothy R D J

2014-10-30

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP. © 2014 by The American Society of Hematology.

In vitro analysis of cytotoxic T cell recruitment mediated by the DC-derived chemokine CCL17

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sprotocols

2015-01-01

Dendritic cell (DC) licensing in cross-priming requires physical interaction of several rare immune cells, i.e. cytotoxic T cells (CTL), and cross-presenting DCs. Here we describe a novel in vitro method of analyzing chemokine effects on complex recruitment events in a multi-cellular system. To study CTL recruitment towards CCL17-producing DCs, we established a co-culture system of murine splenic DCs with polyclonal splenic CTL from donor mice, which enables visualization of cell motility and...

Isolated Splenic Metastasis from Renal Cell Carcinoma: Case Report and Review

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J.A.G. Moir

2011-04-01

Full Text Available This report presents the case of a 70-year-old woman with a previous history of a left nephrectomy for renal cell carcinoma (RCC, who developed general malaise and fatigue. Abdominal computed tomography demonstrated an enhancing 6 × 7 cm necrotic lesion in the lower pole of the spleen suggestive of a metastasis. Given the highly suspicious nature of the lesion we proceeded to splenectomy. The tumour did not breach the splenic capsule, and there was no local diaphragmatic involvement. The mass was concluded to be a true metastasis of the original RCC rather than local recurrence of the disease. The causes of isolated solid splenic lesions are wide and varied, however a past or present history of malignancy should lead to a high index of suspicion for a splenic metastasis. We report an extremely unusual case of spread from a RCC.

Splenic scintigraphy using Tc-99m-labeled heat-denatured red blood cells in pediatric patients: concise communication

International Nuclear Information System (INIS)

Ehrlich, C.P.; Papanicolaou, N.; Treves, S.; Hurwitz, R.A.; Richards, P.

1982-01-01

Ten children underwent splenic imaging with heat-denatured red blood cells labeled with technetium-99m (Tc-99m DRBC). The presenting problems included the heterotaxia syndrome, recurrent idiopathic thrombocytopenic purpura following splenectomy, mass in the left posterior hemithorax, and blunt abdominal trauma. In nine patients, the presence or absence of splenic tissue was established. A splenic hematoma was identified in the tenth patient. All patients were initially scanned with Tc-99m sulfur colloid (Tc-99m SC), and were selected for Tc-99m DRBC scintigraphy only after the results of the SC scans failed to establish the clinical problem beyond doubt. The availability of kits containing stannous ions, essential for efficient and stable labeling of red blood cells with Tc-99m and requiring only a small volume of blood, make splenic scintigraphy in children a relatively simple and definitive diagnostic procedure, when identification of splenic tissue is of clinical importance

Splenic scintigraphy using Tc-99m-labeled heat-denatured red blood cells in pediatric patients: concise communication

Energy Technology Data Exchange (ETDEWEB)

Ehrlich, C.P.; Papanicolaou, N.; Treves, S.; Hurwitz, R.A.; Richards, P.

1982-03-01

Ten children underwent splenic imaging with heat-denatured red blood cells labeled with technetium-99m (Tc-99m DRBC). The presenting problems included the heterotaxia syndrome, recurrent idiopathic thrombocytopenic purpura following splenectomy, mass in the left posterior hemithorax, and blunt abdominal trauma. In nine patients, the presence or absence of splenic tissue was established. A splenic hematoma was identified in the tenth patient. All patients were initially scanned with Tc-99m sulfur colloid (Tc-99m SC), and were selected for Tc-99m DRBC scintigraphy only after the results of the SC scans failed to establish the clinical problem beyond doubt. The availability of kits containing stannous ions, essential for efficient and stable labeling of red blood cells with Tc-99m and requiring only a small volume of blood, make splenic scintigraphy in children a relatively simple and definitive diagnostic procedure, when identification of splenic tissue is of clinical importance.

Acute splenic sequestration in a pregnant woman with homozygous sickle-cell anemia

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Carolina Bastos Maia

Full Text Available CONTEXT Homozygous (SS sickle-cell anemia complicated by acute splenic sequestration in adults is a rare event, and it has never been reported during pregnancy. CASE REPORT A 25-year-old woman with homozygous (SS sickle-cell disease was hospitalized at 32 weeks' of gestation presenting weakness, abdominal pain, fever and hemoglobin of 2.4 g/dl. Abnormal fetal heart rate was detected by means of cardiotocography, and 5 units of packed red cells were transfused. Cesarean was performed at 37 weeks. Both mother and baby were discharged in a good general condition. CONCLUSION This case report demonstrates the importance of immediate blood transfusion for treatment of fetal distress in cases of splenic sequestration during pregnancy. This treatment is essential for avoiding maternal and fetal complications.

Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells

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Fabian eSalazar

2013-11-01

Full Text Available Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells, culminating in mast cell sensitization and triggering. Dendritic cells have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors dendritic cells are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence dendritic cells behaviour through the release of a number of Th2 promoting cytokines. In this review we will summarise current understanding of how allergens are recognised by dendritic cells and epithelial cells and what are the consequences of such interaction in the context of allergic sensitisation and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signalling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitisation hence hindering development or progression of allergic diseases.

Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

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Yi Eunhee S

2010-04-01

Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period.

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Elbe, A; Tschachler, E; Steiner, G; Binder, A; Wolff, K; Stingl, G

1989-10-15

The adult murine epidermis harbors two separate CD45+ bone marrow (BM)-derived dendritic cell systems, i.e., Ia+, ADPase+, Thy-1-, CD3- Langerhans cells (LC) and Ia-, ADPase-, Thy-1+, CD3+ dendritic epidermal T cells (DETC). To clarify whether the maturation of these cells from their ill-defined precursors is already accomplished before their entry into the epidermis or, alternatively, whether a specific epidermal milieu is required for the expression of their antigenic determinants, we studied the ontogeny of CD45+ epidermal cells (EC). In the fetal life, there exists a considerable number of CD45+, Ia-, ADPase+ dendritic epidermal cells. When cultured, these cells become Ia+ and, in parallel, acquire the potential of stimulating allogeneic T cell proliferation. These results imply that CD45+, Ia-, ADPase+ fetal dendritic epidermal cells are immature LC precursors and suggest that the epidermis plays a decisive role in LC maturation. The day 17 fetal epidermis also contains a small population of CD45+, Thy-1+, ADPase-, CD3- round cells. Over the course of 2 to 3 wk, they are slowly replaced by an ever increasing number of round and, finally, dendritic CD45+, Thy-1+, CD3+ EC. Thus, CD45+, Thy-1+, ADPase-, CD3- fetal EC may either be DETC precursors or, alternatively, may represent a distinctive cell system of unknown maturation potential. According to this latter theory, these cells would be eventually outnumbered by newly immigrating CD45+, Thy-1+, CD3+ T cells--the actual DETC.

Burn injury triggered dysfunction in dendritic cell response to TLR9 activation and resulted in skewed T cell functions.

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Haitao Shen

Full Text Available Severe trauma such as burn injury is often associated with a systemic inflammatory syndrome characterized by a hyperactive innate immune response and suppressed adaptive immune function. Dendritic cells (DCs, which sense pathogens via their Toll-like receptors (TLRs, play a pivotal role in protecting the host against infections. The effect of burn injury on TLR-mediated DC function is a debated topic and the mechanism controlling the purported immunosuppressive response remains to be elucidated. Here we examined the effects of burn injury on splenic conventional DC (cDC and plasmacytoid DC (pDC responses to TLR9 activation. We demonstrate that, following burn trauma, splenic cDCs' cytokine production profile in response to TLR9 activation became anti-inflammatory dominant, with high production of IL-10 (>50% increase and low production of IL-6, TNF-α and IL-12p70 (∼25-60% reduction. CD4+ T cells activated by these cDCs were defective in producing Th1 and Th17 cytokines. Furthermore, burn injury had a more accentuated effect on pDCs than on cDCs. Following TLR9 activation, pDCs displayed an immature phenotype with an impaired ability to secrete pro-inflammatory cytokines (IFN-α, IL-6 and TNF-α and to activate T cell proliferation. Moreover, cDCs and pDCs from burn-injured mice had low transcript levels of TLR9 and several key molecules of the TLR signaling pathway. Although hyperactive innate immune response has been associated with severe injury, our data show to the contrary that DCs, as a key player in the innate immune system, had impaired TLR9 reactivity, an anti-inflammatory phenotype, and a dysfunctional T cell-priming ability. We conclude that burn injury induced impairments in DC immunobiology resulting in suppression of adaptive immune response. Targeted DC immunotherapies to promote their ability in triggering T cell immunity may represent a strategy to improve immune defenses against infection following burn injury.

Functional Identification of Dendritic Cells in the Teleost Model, Rainbow Trout (Oncorhynchus mykiss)

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Bassity, Elizabeth; Clark, Theodore G.

2012-01-01

Dendritic cells are specialized antigen presenting cells that bridge innate and adaptive immunity in mammals. This link between the ancient innate immune system and the more evolutionarily recent adaptive immune system is of particular interest in fish, the oldest vertebrates to have both innate and adaptive immunity. It is unknown whether dendritic cells co-evolved with the adaptive response, or if the connection between innate and adaptive immunity relied on a fundamentally different cell type early in evolution. We approached this question using the teleost model organism, rainbow trout (Oncorhynchus mykiss), with the aim of identifying dendritic cells based on their ability to stimulate naïve T cells. Adapting mammalian protocols for the generation of dendritic cells, we established a method of culturing highly motile, non-adherent cells from trout hematopoietic tissue that had irregular membrane processes and expressed surface MHCII. When side-by-side mixed leukocyte reactions were performed, these cells stimulated greater proliferation than B cells or macrophages, demonstrating their specialized ability to present antigen and therefore their functional homology to mammalian dendritic cells. Trout dendritic cells were then further analyzed to determine if they exhibited other features of mammalian dendritic cells. Trout dendritic cells were found to have many of the hallmarks of mammalian DCs including tree-like morphology, the expression of dendritic cell markers, the ability to phagocytose small particles, activation by toll-like receptor-ligands, and the ability to migrate in vivo. As in mammals, trout dendritic cells could be isolated directly from the spleen, or larger numbers could be derived from hematopoietic tissue and peripheral blood mononuclear cells in vitro. PMID:22427987

Massive splenic infarction in Saudi patients with sickle cell anemia: a unique manifestation.

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Jama, Ali Hassan Al; Salem, Ahmed Hassan Al; Dabbous, Ibrahim Abdalla Al

2002-03-01

Splenic infarcts are common in patients with sickle cell anemia (SCA), but these are usually small and repetitive, leading ultimately to autosplenectomy. Massive splenic infarcts on the other hand are extremely rare. This is a report of our experience with 8 (4 males and 4 females) cases of massive splenic infarction in patients with SCA. Their ages ranged from 16 to 36 years (mean 22 years). Three presented with left upper quadrant abdominal pain and massive splenic infarction on admission, while the other 5 developed massive splenic infarction while in hospital. In 5 the precipitating factors were high altitude, postoperative, postpartum, salmonella septicemia, and strenuous exercise in one each, while the remaining 3 had severe generalized vasoocclusive crises. Although both ultrasound and CT scan of the abdomen were of diagnostic value, we found CT scan more accurate in delineating the size of infarction. All our patients were managed conservatively with I.V. fluids, analgesia, and blood transfusion when necessary. Diagnostic aspiration under ultrasound guidance was necessary in two patients to differentiate between massive splenic infarction and splenic abscess. Two patients required splenectomy during the same admission because of suspicion of secondary infection and abscess formation, while a third patient had splenectomy 2 months after the attack because of persistent left upper quadrant abdominal pain. In all the 3 histology of the spleen showed congestive splenomegaly with massive infarction. All of our patients survived. Two patients subsequently developed autosplenectomy while the remaining 3 continue to have persistent but asymptomatic splenomegaly. Massive splenic infarction is a rare and unique complication of SCA in the Eastern Province of Saudi Arabia, and for early diagnosis and treatment, physicians caring for these patients should be aware of such a complication.

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and lymphocytes

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Oluwole, S.F.; Engelstad, K.; De Rosa, C.; Wang, T.S.; Fawwaz, R.A.; Reemtsma, K.; Hardy, M.A. (Columbia Univ., New York, NY (USA))

1991-04-01

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that {sup 111}In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV.

Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

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Julio Aliberti

2016-01-01

Full Text Available Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

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Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

2016-01-01

Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765

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Lifescience Database Archive (English)

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File list: Unc.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

Lifescience Database Archive (English)

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Primary splenic angiosarcoma with liver metastasis: A rare neoplasm diagnosed on fine-needle aspiration cytology and cell block immunocytochemistry

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Saniya Sharma

2018-01-01

Full Text Available Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal origin. The tumor is highly aggressive and has a high metastatic potential. It is usually diagnosed on histopathological examination of splenectomy specimen. Only few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA cytology alone have been reported in the literature. The cytologic features of angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when vasoformative features are present. A 55-year-old female presented with abdominal pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous splenic lesion with liver metastases. FNA from the splenic and liver lesions showed moderately pleomorphic tumor cells closely associated with anastomosing vascular channels. Cell block immunocytochemistry (ICC showed tumor cells positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block ICC can render a definite diagnosis of primary splenic angiosarcoma with liver metastasis.

Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis.

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Alves, C Henrique; Ober-Blöbaum, Julia L; Brouwers-Haspels, Inge; Asmawidjaja, Patrick S; Mus, Adriana M C; Razawy, Wida; Molendijk, Marlieke; Clausen, Björn E; Lubberts, Erik

2015-01-01

Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The β-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of β-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of β-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs) were generated and used to study the maturation profile of these cells in response to a TLR2 or TLR4 ligand stimulation. CIA was induced by intra-dermal immunization with 100 μg chicken type II collagen in complete Freund's adjuvant on days 0 and 21. CIA incidence and severity was monitored macroscopically and by histology. The T cell profile as well as their cytokine production were analysed by flow cytometry. Lack of β-catenin specifically in DCs did not affect the spontaneous, TLR2- or TLR4-induced maturation and activation of BMDCs or their cytokine production. Moreover, no effect on the incidence and severity of CIA was observed in mice lacking β-catenin in CD11c+ cells. A decreased frequency of splenic CD3+CD8+ T cells and of regulatory T cells (Tregs) (CD4+CD25highFoxP3+), but no changes in the frequency of splenic Th17 (CCR6+CXCR3-CCR4+), Th2 (CCR6-CXCR3-CCR4+) and Th1 (CCR6-CXCR3+CCR4-) cells were observed in these mice under CIA condition. Furthermore, the expression of IL-17A, IL-17F, IL-22, IL-4 or IFNγ was also not affected. Our data indicate that ablation of β-catenin expression in DCs did not alter the course and severity of CIA. We conclude that although deletion of β-catenin resulted in a lower frequency of Tregs, this decrease was not sufficient to aggravate the onset and severity of CIA.

Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis.

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C Henrique Alves

Full Text Available Dendritic cells (DCs are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The β-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of β-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA. Deletion of β-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs were generated and used to study the maturation profile of these cells in response to a TLR2 or TLR4 ligand stimulation. CIA was induced by intra-dermal immunization with 100 μg chicken type II collagen in complete Freund's adjuvant on days 0 and 21. CIA incidence and severity was monitored macroscopically and by histology. The T cell profile as well as their cytokine production were analysed by flow cytometry. Lack of β-catenin specifically in DCs did not affect the spontaneous, TLR2- or TLR4-induced maturation and activation of BMDCs or their cytokine production. Moreover, no effect on the incidence and severity of CIA was observed in mice lacking β-catenin in CD11c+ cells. A decreased frequency of splenic CD3+CD8+ T cells and of regulatory T cells (Tregs (CD4+CD25highFoxP3+, but no changes in the frequency of splenic Th17 (CCR6+CXCR3-CCR4+, Th2 (CCR6-CXCR3-CCR4+ and Th1 (CCR6-CXCR3+CCR4- cells were observed in these mice under CIA condition. Furthermore, the expression of IL-17A, IL-17F, IL-22, IL-4 or IFNγ was also not affected. Our data indicate that ablation of β-catenin expression in DCs did not alter the course and severity of CIA. We conclude that although deletion of β-catenin resulted in a lower frequency of Tregs, this decrease was not sufficient to aggravate the onset and severity of CIA.

Sensitivity of Dendritic Cells to Microenvironment Signals

Directory of Open Access Journals (Sweden)

Juliana Maria Motta

2016-01-01

Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

Hepatic natural killer cells exclusively kill splenic/blood natural killer-resistant tumor cells by the perforin/granzyme pathway

NARCIS (Netherlands)

Vermijlen, David; Luo, Dianzhong; Froelich, Christopher J.; Medema, Jan Paul; Kummer, Jean Alain; Willems, Erik; Braet, Filip; Wisse, Eddie

2002-01-01

Hepatic natural killer (NK) cells are located in the liver sinusoids adherent to the endothelium. Human and rat hepatic NK cells induce cytolysis in tumor cells that are resistant to splenic or blood NK cells. To investigate the mechanism of cell death, we examined the capacity of isolated, pure

Chemoresistance of human monocyte-derived dendritic cells is regulated by IL-17A.

Directory of Open Access Journals (Sweden)

Selma Olsson Åkefeldt

Full Text Available Dendritic cells initiate adaptive immune responses, leading either to control cancer by effector T cells or to exacerbate cancer by regulatory T cells that inhibit IFN-γ-mediated Th1-type response. Dendritic cells can also induce Th17-type immunity, mediated by IL-17A. However, the controversial role of this cytokine in cancer requires further investigations. We generated dendritic cells from peripheral blood monocytes to investigate lifespan, phenotype and chemoresistance of dendritic cells, treated with IL-17A with or without IFN-γ. Studying the expression of Bcl-2 family members, we demonstrated that dendritic cells constitutively express one pro-survival Bcl-2 member: MCL1. Immature dendritic cells were CD40(lowHLADR(low CD1a(+ MCL1(+, did not express CD14, CD68 or BCL2A1, and displayed a short 2-day lifespan. IL-17A-treated DC exhibited a semi-mature (CD40(high HLADR(low pre-M2 (CCL22(+ CD206(+ CD163(+ IL1RN(+ IL-10(- CXCL10(- IL-12(- mixed (CD1a(+ CD14+ CD68(+ macrophage-dendritic cell phenotype. They efficiently exerted mannose receptor-mediated endocytosis and did not produce superoxide anions, in the absence of TLR engagement. Interestingly, IL-17A promoted a long-term survival of dendritic cells, beyond 12 days, that correlated to BCL2A1 induction, a pro-survival Bcl-2 family member. BCL2A1 transcription was activated by NF-κB, downstream of IL-17A transduction. Thus, immature dendritic cells only express MCL1, whereas IL-17A-treated dendritic cells concomitantly expressed two pro-survival Bcl-2 family members: MCL1 and BCL2A1. These latter developed chemoresistance to 11 of the 17 chemotherapy agents tested. However, high doses of either vinblastine or cytarabine decreased MCL1 expression and induced dendritic cell death. When IL-17A is produced in vivo, administration of anti-IL-17A biotherapy may impair dendritic cell survival by targeting BCL2A1 expression. Consequently, depending on the effector or regulatory role of dendritic

Splenic abscess after splenic blunt injury angioembolization.

Science.gov (United States)

Tartaglia, Dario; Galatioto, Christian; Lippolis, Piero Vincenzo; Modesti, Matteo; Gianardi, Desirée; Bertolucci, Andrea; Cucinotta, Monica; Zocco, Giuseppe; Seccia, Massimo

2014-11-03

Splenic Angioembolization (SAE), during Nonoperative Management (NOM) of Blunt Splenic Injury (BSI), is an effective therapy for hemodynamically stable patients with grade III, IV, and V OIS splenic injuries. We report a case of a patient with a blunt abdominal trauma due to an accidental fall, who presented splenic abscess a week after SAE and a review of the literature. A 38-year-old male arrived at Emergency after an accidental fall with contusion of the left upper quadrant of the abdomen. Abdominal CT scan revealed the fracture of the lower splenic pole with intraparenchymal pseudoaneurysms (OIS spleen injury scale IV). Considering the hemodynamic stability, NOM was undertaken and SAE was performed. After a week, the patient developed a splenic abscess confirmed by Abdominal CT; therefore, splenectomy was performed. There was no evidence of bacterial growing in the perisplenic hematoma cultures but the histological examination showed multiple abscess and hemorrhagic areas in the spleen. Splenic abscess after SAE during NOM of BSI is a rare major complication. The most frequently cultured organisms include Clostridium perfringens, Alpha-Hemoliticus Streptococcus, gram-positive Staphylococcus, gram-negative Salmonella, Candida, and Aspergillus. This case represents our first reported splenic abscess after SAE. SAE is a very useful tool for BSI managing; splenic abscess can occur in a short time, even if it is a rare major complication, so it may be useful to monitor patients undergoing SAE, focusing not only on the hemodynamic parameters but also on the inflammatory and infectious aspects.

Dendritic branching of olfactory bulb mitral and tufted cells: regulation by TrkB.

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Fumiaki Imamura

2009-08-01

Full Text Available Projection neurons of mammalian olfactory bulb (OB, mitral and tufted cells, have dendrites whose morphologies are specifically differentiated for efficient odor information processing. The apical dendrite extends radially and arborizes in single glomerulus where it receives primary input from olfactory sensory neurons that express the same odor receptor. The lateral dendrites extend horizontally in the external plexiform layer and make reciprocal dendrodendritic synapses with granule cells, which moderate mitral/tufted cell activity. The molecular mechanisms regulating dendritic development of mitral/tufted cells is one of the unsolved important problems in the olfactory system. Here, we focused on TrkB receptors to test the hypothesis that neurotrophin-mediate mechanisms contributed to dendritic differentiation of OB mitral/tufted cells.With immunohistochemical analysis, we found that the TrkB neurotrophin receptor is expressed by both apical and lateral dendrites of mitral/tufted cells and that expression is evident during the early postnatal days when these dendrites exhibit their most robust growth and differentiation. To examine the effect of TrkB activation on mitral/tufted cell dendritic development, we cultured OB neurons. When BDNF or NT4 were introduced into the cultures, there was a significant increase in the number of primary neurites and branching points among the mitral/tufted cells. Moreover, BDNF facilitated filopodial extension along the neurites of mitral/tufted cells.In this report, we show for the first time that TrkB activation stimulates the dendritic branching of mitral/tufted cells in developing OB. This suggests that arborization of the apical dendrite in a glomerulus is under the tight regulation of TrkB activation.

Immunologic effects of whole body ultraviolet (uv) irradiation. II. Defect in splenic adherent cell antigen presentation for stimulation of T cell proliferation

International Nuclear Information System (INIS)

Letvin, N.L.; Fox, I.J.; Greene, M.I.; Benacerraf, B.; Germain, R.N.

1980-01-01

Ultraviolet (uv) irradiation has been shown to alter many parameters of the immunologic reactivity of mice. The altered responsiveness of uv-irradiated mice, as measured by delayed-type hypersensitivity (DTH) and primary in vitro plaque-forming cell (PFC) responses to T-dependent antigens, has recently been correlated with a functional defect in the splenic adherent cell population of these animals. The present studies describe a model of this altered responsiveness, which allows further clarification of the effects of external uv irradiation on the splenic antigen-presenting cell (APC) in its interactions with T cells

Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

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Félicien Moukambi

2015-12-01

Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

Dendritic cells modified by vitamin D

DEFF Research Database (Denmark)

Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

2011-01-01

Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell ...

Resistance to RadLV-induced leukemia: non-participation of splenic natural killer cells

International Nuclear Information System (INIS)

St-Pierre, Y.; Hugo, P.; Lemieux, S.; Lussier, G.; Potworowski, E.F.

1988-01-01

The phenotypic expression of genetically determined resistance to radiation leukemia virus (RadLV)-induced leukemia in mice has been shown to reside in the bone marrow. Because the bone marrow contains precursors of natural killer (NK) cells, known to play a role in retrovirally induced infections, and because these cells have been suggested as participating in resistance to radiation-induced leukemia, it was pertinent to establish whether their levels differed in strains of mice susceptible and resistant to leukemia. We therefore tested splenic NK cell levels in C57BL/Ka (susceptible) and B10.A(5R) (resistant) mice before viral inoculation, immediately after viral inoculation, and throughout the preleukemic period and showed that they were not different. This indicates that splenic NK cell levels have no bearing on the resistance to RadLV-induced leukemia and that other immune or non-immune mechanisms must be sought

Dendritic cells: biology of the skin

NARCIS (Netherlands)

Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

2009-01-01

Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

File list: InP.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.10.AllAg.Dendritic_Cells hg19 Input control Blood Dendritic Cells SRX627429...,SRX627427 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.10.AllAg.Dendritic_Cells.bed ...

Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.

Science.gov (United States)

Philippe, Laure; Ceroi, Adam; Bôle-Richard, Elodie; Jenvrin, Alizée; Biichle, Sabeha; Perrin, Sophie; Limat, Samuel; Bonnefoy, Francis; Deconinck, Eric; Saas, Philippe; Garnache-Ottou, Francine; Angelot-Delettre, Fanny

2017-11-01

Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematologic malignancy with a poor prognosis. No consensus regarding optimal treatment modalities is currently available. Targeting the nuclear factor-kappa B pathway is considered a promising approach since blastic plasmacytoid dendritic cell neoplasm has been reported to exhibit constitutive activation of this pathway. Moreover, nuclear factor-kappa B inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines, achieved using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib, interferes in vitro with leukemic cell proliferation and survival. Here we extended these data by showing that primary blastic plasmacytoid dendritic cell neoplasm cells from seven patients were sensitive to bortezomib-induced cell death. We confirmed that bortezomib efficiently inhibits the phosphorylation of the RelA nuclear factor-kappa B subunit in blastic plasmacytoid dendritic cell neoplasm cell lines and primary cells from patients in vitro and in vivo in a mouse model. We then demonstrated that bortezomib can be associated with other drugs used in different chemotherapy regimens to improve its impact on leukemic cell death. Indeed, when primary blastic plasmacytoid dendritic cell neoplasm cells from a patient were grafted into mice, bortezomib treatment significantly increased the animals' survival, and was associated with a significant decrease of circulating leukemic cells and RelA nuclear factor-kappa B subunit expression. Overall, our results provide a rationale for the use of bortezomib in combination with other chemotherapy for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm. Based on our data, a prospective clinical trial combining proteasome inhibitor with classical drugs could be envisaged. Copyright© Ferrata Storti Foundation.

The clinical significance of T-cells, sIL-2R and TNF in evaluating patients with splenic autotransplantation

International Nuclear Information System (INIS)

Wang Haowei; Wu Haorong; Li Juncheng; Wu Jingchang

2002-01-01

To study the immunological effects of splenic autotransplantation, forty patients with splenic trauma were divided into two groups equally. One group underwent splenic autotransplantation and another underwent splenectomy. Control group included ten cases. Splenic autotransplantation and splenectomy group were compared with the control group. In the group of splenic autotransplantation, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + dropped and sIL-2R, TNF rose after a week of operation. Then CD3 + , CD4 + , CD8 + , CD4 + /CD8 + rose and sIL-2R, TNF dropped three months later. In the group of splenectomy, CD 3+ , CD4 + , CD8 + and CD4 + /CD8 + dropped persistently, while sIL-2R and TNF rose postoperatively. Result showed splenic autotransplantation can help body to maintain T-cells level and improve the anti-infective ability

Xenopus laevis Retinal Ganglion Cell Dendritic Arbors Develop Independently of Visual Stimulation

Directory of Open Access Journals (Sweden)

Barbara Lom

2004-01-01

Full Text Available Newly formed neurons must locate their appropriate target cells and then form synaptic connections with these targets in order to establish a functional nervous system. In the vertebrate retina, retinal ganglion cell (RGC dendrites extend from the cell body and form synapses with nearby amacrine and bipolar cells. RGC axons, however, exit the retina and synapse with the dendrites of midbrain neurons in the optic tectum. We examined how visual stimulation influenced Xenopus RGC dendritic arborization. Neuronal activity is known to be an important factor in shaping dendritic and axonal arborization. Thus, we reared tadpoles in dark and light environments then used rhodamine dextran retrograde labeling to identify RGCs in the retina. When we compared RGC dendritic arbors from tadpoles reared in dark and light environments, we found no morphological differences, suggesting that physiological visual activity did not contribute to the morphological development of Xenopus RGC dendritic arbors.

Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

Directory of Open Access Journals (Sweden)

Hermann Cuntz

2014-03-01

Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

[Effect of electroacupuncture on differentiation and proliferation of hippocampal nerve stem cells in splenic asthenia pedo-rats].

Science.gov (United States)

Zhuo, Yuan-yuan; Yang, Zhuo-xin; Wu, Jia-man

2011-10-01

To observe the effect of electroacupuncture (EA) on the differentiation and proliferation of nerve stem cells in the hippocampal dentate gyrus (DG) in splenic asthenia pedo-rats so as to study its central mechanism. A total of 72 SD male rats were randomly assigned to normal control group (n=24), model group (n=24) and EA group (n=24) which were further divided into 7 d, 14 d, 28 d and 49 d time-points (n=6). Splenic asthenia model was established by intraperitoneal injection of reserpine and gavage of Dahuang (Radix et Rhizoma Rhei) fluid. EA was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 min, once daily for 7, 14, 28 and 49 days respectively. Brdu, Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE) expression in the DG of hippocampus were detected by immunohistochemistry double staining. Compared with the normal control group, the numbers of Brdu, Brdu/GFAP, Brdu/NSE Immunoreactive (IR) positive cells in the DG of hippocampus on day 7 and 14, and that of Brdu/Nestin IR-positive cells on day 7 were decreased considerably in the model group (P 0.05). EA of ST 36 and SP 6 can effectively suppress splenic asthenia syndrome-induced decrease of the numbers of Brdu, Brdu/GFAP, Brdu/Nestin and Brdu/NSE IR-positive cells in the DG of hippocampus at the early stage in the splenic asthenia rats, which may contribute to its effect in improving splenic asthenia symptoms in clinic by promoting the proliferation and differentiation of some nerve stem cells in the hippocampus.

A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

Science.gov (United States)

Hancock, David G; Shklovskaya, Elena; Guy, Thomas V; Falsafi, Reza; Fjell, Chris D; Ritchie, William; Hancock, Robert E W; Fazekas de St Groth, Barbara

2014-01-01

Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS) provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

Antigen dynamics of follicular dendritic cells

NARCIS (Netherlands)

Heesters, B.A.

2015-01-01

Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

File list: InP.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.05.AllAg.Dendritic_Cells mm9 Input control Blood Dendritic Cells SRX885956,...76,SRX122481,SRX667880,SRX667874,SRX667878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Dendritic_Cells.bed ...

p16 expression in follicular dendritic cell sarcoma: a potential mimicker of human papillomavirus-related oropharyngeal squamous cell carcinoma.

Science.gov (United States)

Zhang, Lingxin; Yang, Chen; Lewis, James S; El-Mofty, Samir K; Chernock, Rebecca D

2017-08-01

Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm that most commonly occurs in cervical lymph nodes. It has histologic and clinical overlap with the much more common p16-positive human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx, which characteristically has nonkeratinizing morphology and often presents as an isolated neck mass. Not surprisingly, follicular dendritic cell sarcomas are commonly misdiagnosed as squamous cell carcinoma. Immunohistochemistry is helpful in separating the 2 entities. Follicular dendritic cell sarcoma expresses dendritic markers such as CD21 and CD23 and is almost always cytokeratin negative. However, in many cases of HPV-related oropharyngeal carcinoma, only p16 immunohistochemistry as a prognostic and surrogate marker for HPV is performed. p16 expression in follicular dendritic cell sarcoma has not been characterized. Here, we investigate the expression of p16 in follicular dendritic cell sarcoma and correlate it with retinoblastoma protein expression. A pilot study of dendritic marker expression in HPV-related oropharyngeal squamous cell carcinoma was also performed. We found that 4 of 8 sarcomas expressed p16 with strong and diffuse staining in 2 cases. In 2 of the 4 cases, p16 expression corresponded to loss of retinoblastoma protein expression. Dendritic marker expression (CD21 and CD23) was not found in HPV-related oropharyngeal squamous cell carcinomas. As such, positive p16 immunohistochemistry cannot be used as supportive evidence for the diagnosis of squamous cell carcinoma as strong and diffuse p16 expression may also occur in follicular dendritic cell sarcoma. Cytokeratins and dendritic markers are critical in separating the two tumor types. Copyright © 2017 Elsevier Inc. All rights reserved.

Dendritic cells in peripheral tolerance and immunity

DEFF Research Database (Denmark)

Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

2003-01-01

Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

Anti tumor vaccination with hybrid dendritic-tumour cells

International Nuclear Information System (INIS)

Barbuto, Jose Alexandre M.; Neves, Andreia R.; Ensina, Luis Felipe C.; Anselmo, Luciene B.

2005-01-01

Dendritic cells are the most potent antigen-presenting cells, and the possibility of their use for cancer vaccination has renewed the interest in this therapeutic modality. Nevertheless, the ideal immunization protocol with these cells has not been described yet. In this paper we describe the preliminary results of a protocol using autologous tumor and allogeneic dendritic hybrid cell vaccination every 6 weeks, for metastatic melanoma and renal cell carcinoma (RCC) patients. Thirty-five patients were enrolled between March 2001 and March 2003. Though all patients included presented with large tumor burdens and progressive diseases, 71% of them experienced stability after vaccination, with durations up to 19 months. Among RCC patients 3/22 (14%) presented objective responses. The median time to progression was 4 months for melanoma and 5.7 months for RCC patients; no significant untoward effects were noted. Furthermore, immune function, as evaluated by cutaneous delayed-type hypersensitivity reactions to recall antigens and by peripheral blood proliferative responses to tumor-specific and nonspecific stimuli, presented a clear tendency to recover in vaccinated patients. These data indicate that dendritic cell-tumor cell hybrid vaccination affects the natural history of advanced cancer and provide support for its study in less advanced patients, who should, more likely, benefit even more from this approach. (author)

DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology

NARCIS (Netherlands)

Geijtenbeek, Teunis B. H.; Engering, Anneke; van Kooyk, Yvette

2002-01-01

Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing

Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

Directory of Open Access Journals (Sweden)

Satoko Arai

2013-04-01

Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

Effects of burn with and without Escherichia coli infection in rats on intestinal vs. splenic T-cell responses.

Science.gov (United States)

Ravindranath, T; Al-Ghoul, W; Namak, S; Fazal, N; Durazo-Arvizu, R; Choudhry, M; Sayeed, M M

2001-12-01

To evaluate the effect of burn injury with and without an Escherichia coliseptic complication on T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses in intestinal Peyer's patch and splenic T cells. Prospective, randomized, sham-controlled animal study. University medical center research laboratory. Adult male Sprague-Dawley rats. Rats were subjected to a 30% total body surface area, full skin thickness burn. Infection in rats was induced via intraperitoneal inoculation of E. coli, 10(9) colony forming units/kg, with or without a prior burn. Rat Peyer's patch and splenic T lymphocytes were isolated by using a nylon wool cell purification protocol. T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses were measured after stimulation of cells with the mitogen, concanavalin A. T-cell proliferation was determined by measuring incorporation of (3)H-thymidine into T-cell cultures. Interleukin-2 production by T-cell cultures was measured by using enzyme-linked immunosorbent assay. Intracellular T-cell Ca2(+ )concentration, [Ca(2+)](i), was measured by the use of Ca(2+)-specific fluorescent label, fura-2, and its fluorometric quantification. [Ca(2+)](i) was also evaluated by the use of digital video imaging of fura-2 loaded individual T cells. T-cell proliferation and interleukin-2 production were suppressed substantially in both Peyer's patch and splenic T cells 3 days after either the initial burn alone or burn followed by the E. coli inoculation at 24 hrs after the initial burn. There seemed to be no demonstrable additive effects of E. coli infection on the effects produced by burn injury alone. The T-cell proliferation and interleukin-2 production suppressions with burn or burn-plus-infection insults were correlated with attenuated Ca(2+) signaling. E. coli infection alone suppressed T-cell proliferation in Peyer's patch but not in splenic T cells at 2 days postbacterial inoculation; E. coli infection had no effect on

Tumor-Mediated Suppression of Dendritic Cell Vaccines

National Research Council Canada - National Science Library

Akporiaye, Emmanuel

2004-01-01

.... One of these factors is Transforming Growth Factor-beta (TGF-beta). TGF-beta is produced in large quantities by different types of cancer including breast cancer and inhibits the actions of several immune cells including dendritic cells (DC...

Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells.

Science.gov (United States)

Curti, Antonio; Trabanelli, Sara; Onofri, Chiara; Aluigi, Michela; Salvestrini, Valentina; Ocadlikova, Darina; Evangelisti, Cecilia; Rutella, Sergio; De Cristofaro, Raimondo; Ottaviani, Emanuela; Baccarani, Michele; Lemoli, Roberto M

2010-12-01

The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein. These data identify

Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells.

NARCIS (Netherlands)

Berk, L.C.J. van den; Roelofs, H.; Huijs, T.; Siebers-Vermeulen, K.G.C.; Raymakers, R.A.P.; Kogler, G.; Figdor, C.G.; Torensma, R.

2009-01-01

Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord

Investigations of the functional states of dendritic cells under different conditioned microenvironments by Fourier transformed infrared spectroscopy.

Science.gov (United States)

Dong, Rong; Long, Jinhua; Xu, Xiaoli; Zhang, Chunlin; Wen, Zongyao; Li, Long; Yao, Weijuan; Zeng, Zhu

2014-01-10

Dendritic cells are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. The dendritic cell-based vaccination against cancer has been clinically achieved promising successes. But there are still many challenges in its clinical application, especially for how to identify the functional states. The CD14+ monocytes were isolated from human peripheral blood after plastic adherence and purified to approximately 98% with cocktail immunomagnetic beads. The immature dendritic cells and mature dendritic cells were induced by traditional protocols. The resulting dendritic cells were cocultured with normal cells and cancer cells. The functional state of dendritic cells including immature dendritic cells (imDCs) and mature dendritic cells (mDCs) under different conditioned microenvironments were investigated by Fourier transformed infrared spectroscopy (FTIR) and molecular biological methods. The results of Fourier transformed infrared spectroscopy showed that the gene transcription activity and energy states of dendritic cells were specifically suppressed by tumor cells (P Fourier transformed infrared spectroscopy at given wave numbers were closely correlated with the expression levels of NF-κB (R2:0.69 and R2:0.81, respectively). Our results confirmed that the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were positively correlated with the expression levels of NF-κB, suggesting that Fourier transformed infrared spectroscopy technology could be clinically applied to identify the functional states of dendritic cell when performing dendritic cell-based vaccination. It's significant for the simplification and standardization of dendritic cell-based vaccination clinical preparation protocols.

Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant Arthritis.

Science.gov (United States)

Wang, Yang; Han, Chen-Chen; Cui, Dongqian; Luo, Ting-Ting; Li, Yifan; Zhang, Yuwen; Ma, Yang; Wei, Wei

2018-06-01

Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti-inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA) rats, but the role of the spleen function is still unclear. The aim of this study was to research how CP-25 regulated spleen function of AA rats. Male Sprague-Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29 after immunization. The spleen histopathological changes were analyzed by hematoxylin-eosin staining. G protein-coupled receptor kinases (GRKs) and prostaglandin receptor subtypes (EPs) were screened by Western blot and immunohistochemistry. The co-expression of GRK2 and EP2 as well as GRK2 and EP4 was measured by immunofluorescence and co-immunoprecipitation. The expression of GRK2 and EP4 in splenic T cells was further detected by immunofluorescence. CP-25 was found to relieve the secondary paw swelling, attenuate histopathologic changes, and downregulate GRK2, EP2 and EP4 expression in AA rats. Additionally, CP-25 not only downregulated the co-expression of GRK2 and EP4 but also downregulated GRK2, EP4 expression in splenic T cells of AA rats. From these results, we can infer that CP-25 play an anti-inflammatory and immune function by affecting the function of the splenic T cells.

Using magnetic resonance imaging to evaluate dendritic cell-based vaccination.

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Peter M Ferguson

Full Text Available Cancer immunotherapy with antigen-loaded dendritic cell-based vaccines can induce clinical responses in some patients, but further optimization is required to unlock the full potential of this strategy in the clinic. Optimization is dependent on being able to monitor the cellular events that take place once the dendritic cells have been injected in vivo, and to establish whether antigen-specific immune responses to the tumour have been induced. Here we describe the use of magnetic resonance imaging (MRI as a simple, non-invasive approach to evaluate vaccine success. By loading the dendritic cells with highly magnetic iron nanoparticles it is possible to assess whether the injected cells drain to the lymph nodes. It is also possible to establish whether an antigen-specific response is initiated by assessing migration of successive rounds of antigen-loaded dendritic cells; in the face of a successfully primed cytotoxic response, the bulk of antigen-loaded cells are eradicated on-route to the node, whereas cells without antigen can reach the node unchecked. It is also possible to verify the induction of a vaccine-induced response by simply monitoring increases in draining lymph node size as a consequence of vaccine-induced lymphocyte trapping, which is an antigen-specific response that becomes more pronounced with repeated vaccination. Overall, these MRI techniques can provide useful early feedback on vaccination strategies, and could also be used in decision making to select responders from non-responders early in therapy.

Born-again spleen. Return of splenic function after splenectomy for trauma

International Nuclear Information System (INIS)

Pearson, H.A.; Johnston, D.; Smith, K.A.; Touloukian, R.J.

1978-01-01

We assessed splenic activity after splenectomy by interference phase microscopical examination of circulating red cells. Normal eusplenic children had a low number (<1%) of red cells with surface indentations or pits. About 20% of red cells of children who had electively been subjected to splenectomy for hematologic indications were pitted. Thirteen of 22 children who had had emergency splenectomy because of traumatic injury had a low percentage of pitted red cells, suggesting a return of splenic function. In five of these children a /sup 99m/Tc sulfur colloid scan demonstrated multiple nodules of recurrent splenic tissue. In contrast to the prevailing opinion that splenosis is rare, we have found it to be a frequent occurrence. Return of splenic function may, in part, account for the low frequency with which overwhelming bacterial sepsis and meningitis have been documented after splenectomy for traumatic indications

Comparison of immunological characteristics of peripheral, splenic and tonsilar naïve B cells by differential gene expression meta-analyses.

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Chokeshai-u-saha, Kaj; Lepoivre, Cyrille; Grieco, Luca; Nguyen, Catherine; Ruxrungtham, Kiat

2012-12-01

Naïve B cells isolated from peripheral blood, spleen and tonsil are commonly used in human B cell studies. However, little has been written about their possible variations in immunological properties. This study compared differential gene expression in human naive B subsets by meta-analysis using expression data available in Gene Expression Onimbus (GEO). Gene expression files of the Affymetrix Human Genome U133A Array (Affymetrix) were downloaded to collect 21 total array data samples of peripheral naïve B cells (n=10), splenic naïve B cells (n=2), tonsilar naïve B cells (n=3), peripheral memory B cells (n=4) and splenic memory B cells (n=2). Prior to differential gene expression analyses, data were normalized in order to reduce non-biological variation among the datasets. Comparisons of peripheral naive B cells with their splenic and tonsilar counterparts showed remarkable differences in terms of gene expression (29 and 202 genes, respectively). However, only minor differences were detected between splenic and tonsilar naive B cells (10 genes), consistent with the clustering results classifying both of them as lymphoid naive B cells. Differential gene expression results also implied higher stimulating states of lymphoid naive B cells when compared with peripheral blood naive B cells. These included enhanced expressions of CD27, CR2, EGR1, GADD45B, ICAM1, ICOSLG, IGHA, IL6, MMP9, SAMSN1, SMAD7, TNFAIP3, but reduced HLA-DOB expression. Our findings suggest that results generated from peripheral naive B cells may not always be applicable to the biological activities of other lymphoid naïve B cells. Nonetheless, further biological study is warranted.

RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

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Taylor, Caitlin A.; Yan, Jing; Howell, Audrey S.; Dong, Xintong; Shen, Kang

2015-01-01

The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1. PMID:26633194

Memory CD8+ T cells protect dendritic cells from CTL killing

NARCIS (Netherlands)

Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

2008-01-01

CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in

Spatial distribution of excitatory synapses on the dendrites of ganglion cells in the mouse retina.

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Yin-Peng Chen

Full Text Available Excitatory glutamatergic inputs from bipolar cells affect the physiological properties of ganglion cells in the mammalian retina. The spatial distribution of these excitatory synapses on the dendrites of retinal ganglion cells thus may shape their distinct functions. To visualize the spatial pattern of excitatory glutamatergic input into the ganglion cells in the mouse retina, particle-mediated gene transfer of plasmids expressing postsynaptic density 95-green fluorescent fusion protein (PSD95-GFP was used to label the excitatory synapses. Despite wide variation in the size and morphology of the retinal ganglion cells, the expression of PSD95 puncta was found to follow two general rules. Firstly, the PSD95 puncta are regularly spaced, at 1-2 µm intervals, along the dendrites, whereby the presence of an excitatory synapse creates an exclusion zone that rules out the presence of other glutamatergic synaptic inputs. Secondly, the spatial distribution of PSD95 puncta on the dendrites of diverse retinal ganglion cells are similar in that the number of excitatory synapses appears to be less on primary dendrites and to increase to a plateau on higher branch order dendrites. These observations suggest that synaptogenesis is spatially regulated along the dendritic segments and that the number of synaptic contacts is relatively constant beyond the primary dendrites. Interestingly, we also found that the linear puncta density is slightly higher in large cells than in small cells. This may suggest that retinal ganglion cells with a large dendritic field tend to show an increased connectivity of excitatory synapses that makes up for their reduced dendrite density. Mapping the spatial distribution pattern of the excitatory synapses on retinal ganglion cells thus provides explicit structural information that is essential for our understanding of how excitatory glutamatergic inputs shape neuronal responses.

Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

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Jaworski JM

2015-02-01

Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

Dendritic-cell control of pathogen-driven T-cell polarization

NARCIS (Netherlands)

Kapsenberg, Martien L.

2003-01-01

Dendritic cells (DCs) are central in the orchestration of the various forms of immunity and tolerance. Their immunoregulatory role mainly relies on the ligation of specific receptors that initiate and modulate DC maturation resulting in the development of functionally different effector DC subsets

Clinical application of dendritic cells in cancer vaccination therapy

DEFF Research Database (Denmark)

Svane, Inge Marie; Soot, Mette Line; Buus, Søren

2003-01-01

During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...

Dendrite short-circuit and fuse effect on Li/polymer/Li cells

International Nuclear Information System (INIS)

Rosso, Michel; Brissot, Claire; Teyssot, Anna; Dolle, Mickael; Sannier, Lucas; Tarascon, Jean-Marie; Bouchet, Renaud; Lascaud, Stephane

2006-01-01

We report on experimental and theoretical studies of dendritic growth in Li/polymer/Li symmetric cells. Potential evolution with time, impedance and in situ microscopy experiments enable to characterise the onset and evolution of dendrites. In particular we observe that dendrites may burn when a high enough current goes through them, a thermo-fusible effect predicted in a previous paper and confirmed by SEM experiments. We present a calculation that gives a quantitative description of this effect: our results enable to understand a series of experimental data published in the literature concerning impedance variations observed while cycling lithium-polymer cells

Epidermotropic presentation by splenic B-cell lymphoma: The importance of clinical-pathologic correlation.

Science.gov (United States)

Hedayat, Amin A; Carter, Joi B; Lansigan, Frederick; LeBlanc, Robert E

2018-04-01

There are exceedingly rare reports of patients with epidermotropic B-cell lymphomas. A subset presented with intermittent, variably pruritic papular eruptions and involvement of their spleens, peripheral blood and bone marrow at the time of diagnosis. Furthermore, some experienced an indolent course despite dissemination of their lymphomas. We report a 66-year-old woman with a 12-year history of intermittent eruptions of non-pruritic, salmon-colored papules on her torso and proximal extremities that occurred in winter and resolved with outdoor activity in spring. Skin biopsy revealed an epidermotropic B-cell lymphoma with a non-specific B-cell phenotype and heavy chain class switching with IgG expression. On workup, our patient exhibited mild splenomegaly and low-level involvement of her peripheral blood and bone marrow by a kappa-restricted B-cell population. A splenic B-cell lymphoma was diagnosed. Considering her longstanding history and absences of cytopenias, our patient has been followed without splenectomy or systemic therapy. Furthermore, the papules have responded dramatically to narrowband UVB. Our case and a review of similar rare reports aim to raise awareness among dermatopathologists and dermatologists of a clinically distinct and indolent subset of epidermotropic splenic lymphomas with characteristic clinical and histologic findings. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alkylglycerols modulate the proliferation and differentiation of non-specific agonist and specific antigen-stimulated splenic lymphocytes.

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Linxi Qian

Full Text Available Alkylglycerols (AKGs are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg. Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL transcription of IgG (γ1 mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1/GATA-3 (Th2 flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2. It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1 and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10 were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations*

Science.gov (United States)

Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; de Souza, Mair Pedro; Orti-Raduan, Érica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease. PMID:25054751

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations.

Science.gov (United States)

Botari, Clara Marino Espricigo; Nunes, Adauto José Ferreira; Souza, Mair Pedro de; Orti-Raduan, Erica Sinara Lenharo; Salvio, Ana Gabriela

2014-01-01

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Burn injury suppresses human dermal dendritic cell and Langerhans cell function

NARCIS (Netherlands)

van den Berg, Linda M.; de Jong, Marein A. W. P.; Witte, Lot de; Ulrich, Magda M. W.; Geijtenbeek, Teunis B. H.

2011-01-01

Human skin contains epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) that are key players in induction of adaptive immunity upon infection. After major burn injury, suppressed adaptive immunity has been observed in patients. Here we demonstrate that burn injury affects adaptive

Double negative (CD3+ 4- 8- TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.

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Beverly Duncan

2010-07-01

Full Text Available Double negative CD3(+4(-8(- TCR alphabeta splenic cells (DNCD3 can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic beta-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes.DNCD3 splenic cells from young NOD mice (1 provided long-lasting protection against diabetes transfer in NOD/Scid immunodeficient mice, (2 proliferated and differentiated in the spleen and pancreas of NOD/Scid mice and pre-diabetic NOD mice into IL-10-secreting T(R-1 like cells in a Th2-like environment, and (3 their anti-diabetogenic phenotype is CD3(+(CD4(-CD8(-CD28(+CD69(+CD25(low Foxp3(- iCTLA-4(-TCR alphabeta(+ with a predominant Vbeta13 gene usage.These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4(+CD25(high Foxp3(+T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.

Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.

Science.gov (United States)

Loveland, Bruce E; Zhao, Anne; White, Shane; Gan, Hui; Hamilton, Kate; Xing, Pei-Xiang; Pietersz, Geoffrey A; Apostolopoulos, Vasso; Vaughan, Hilary; Karanikas, Vaios; Kyriakou, Peter; McKenzie, Ian F C; Mitchell, Paul L R

2006-02-01

Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy. Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy. Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment. Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.

Involvement of dendritic cells in allograft rejection new implications of dendritic cell-endothelial cell interactions.

Science.gov (United States)

Schlichting, C L; Schareck, W D; Kofler, S; Weis, M

2007-04-01

For almost half a century immunologists have tried to tear down the MHC barrier, which separates two unrelated individuals during transplantation. Latest experimental data suggest that a breakthrough in vitro is imminent. Dendritic cells (DCs), which activate naïve allo-reactive T-cells (TCs), play a central role in the establishment of allo-antigen-specific immunity. Allograft solid organ rejection is initiated at the foreign endothelial cell (EC) layer, which forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might play a crucial role in antigen-specific allograft rejection. Organ rejection is mediated by host allo-reactive TCs, which are activated by donor DCs (direct activation) or host DCs (indirect activation). Direct allo-antigen presentation by regulatory dendritic cells (DCreg) can play an instructive role towards tolerance induction. Several groups established that, DCregs, if transplanted beforehand, enter host thymus, spleen, or bone marrow where they might eventually establish allo-antigen-specific tolerance. A fundamental aspect of DC function is migration throughout the entire organism. After solid organ transplantation, host DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid vessels and secondary lymphoid organs, where they present allo-antigens to naïve host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo-transplantation tolerance induction. However, the fundamental mechanisms on how such DCregs cause host TCs in the periphery towards tolerance remain unclear. One very promising experimental concept is the simultaneous manipulation of DC direct and indirect TC activation/suppression, towards donor antigen-specific allo-transplantation tolerance. The allo-antigen-specific long-term tolerance induction mediated by DCreg pre-transplantation (with simultaneous short-term immunosuppression) has become reproducible in the laboratory animal setting. Despite the shortcomings

A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

OpenAIRE

Asfaw, Sofya H.; Falk, Gavin A.; Morris-Stiff, Gareth; Tuthill, Ralph J.; Moorman, Matthew L.; Samotowka, Michael A.

2013-01-01

Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem org...

Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

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Der-Yuan Chen

2013-01-01

Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

Delayed splenic vascular injury after nonoperative management of blunt splenic trauma.

Science.gov (United States)

Furlan, Alessandro; Tublin, Mitchell E; Rees, Mitchell A; Nicholas, Dederia H; Sperry, Jason L; Alarcon, Louis H

2017-05-01

Delayed splenic vascular injury (DSVI) is traditionally considered a rare, often clinically occult, harbinger of splenic rupture in patients with splenic trauma that are managed conservatively. The purpose of our study was to assess the incidence of DSVI and associated features in patients admitted with blunt splenic trauma and managed nonoperatively. A retrospective analysis was conducted over a 4-y time. Patients admitted with blunt splenic trauma, managed no-operatively and with a follow-up contrast-enhanced computed tomography (CT) scan study during admission were included. The CT scans were reviewed for American Association for the Surgery of Trauma splenic injury score, amount of hemoperitoneum, and presence of DSVI. Logistic regression models were used to investigate the risk factors associated with DSVI. A total of 100 patients (60 men and 40 women) constituted the study group. Follow-up CT scan demonstrated a 23% incidence of DSVI. Splenic artery angiography validated DSVI in 15% of the total patient population. Most DSVIs were detected only on arterial phase CT scan imaging. The American Association for the Surgery of Trauma splenic injury score (odds ratio = 1.73; P = 0.045) and the amount of hemoperitoneum (odds ratio = 1.90; P = 0.023) on admission CT scan were associated with the development of DSVI on follow-up CT scan. DSVI on follow-up CT scan imaging of patients managed nonoperatively after splenic injury is common and associated with splenic injury score assessed on admission CT scan. Copyright © 2016 Elsevier Inc. All rights reserved.

Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

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Joris D. Veltman

2010-01-01

Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

Genetically engineered dendritic cell-based cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2001-01-01

Roč. 18, č. 3 (2001), s. 475-478 ISSN 1019-6439 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.330, year: 2001

Genetically modified dendritic cell-based cancer vaccines

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2001-01-01

Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

Energy Technology Data Exchange (ETDEWEB)

Santos, Allan [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil); Servico de Medicina Nuclear, Hospital das Clinicas da UNICAMP, Campina (Brazil); Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia [Centro Infantil Domingos A. Boldrini, Campinas (Brazil); Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E. [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil)

2002-04-01

Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with S{beta}{sup 0} haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one S{beta}{sup 0} patient and impaired splenic function in five SS patients and six S{beta}{sup 0} patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

International Nuclear Information System (INIS)

Santos, Allan; Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia; Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E.

2002-01-01

Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with Sβ 0 haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one Sβ 0 patient and impaired splenic function in five SS patients and six Sβ 0 patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

Charged particle mutagenesis at low dose and fluence in mouse splenic T cells

Energy Technology Data Exchange (ETDEWEB)

Grygoryev, Dmytro [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Gauny, Stacey [Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Lasarev, Michael; Ohlrich, Anna [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Kronenberg, Amy [Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Turker, Mitchell S., E-mail: turkerm@ohsu.edu [Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239 (United States); Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239 (United States)

2016-06-15

Highlights: • Densely ionizing forms of space radiation induce mutations in splenic T cells at low fluence. • Large interstitial deletions and discontinuous LOH patterns are radiation signature mutations. • Space radiation mutagenesis suggests a cancer risk from deep space travel. - Abstract: High-energy heavy charged particles (HZE ions) found in the deep space environment can significantly affect human health by inducing mutations and related cancers. To better understand the relation between HZE ion exposure and somatic mutation, we examined cell survival fraction, Aprt mutant frequencies, and the types of mutations detected for mouse splenic T cells exposed in vivo to graded doses of densely ionizing {sup 48}Ti ions (1 GeV/amu, LET = 107 keV/μm), {sup 56}Fe ions (1 GeV/amu, LET = 151 keV/μm) ions, or sparsely ionizing protons (1 GeV, LET = 0.24 keV/μm). The lowest doses for {sup 48}Ti and {sup 56}Fe ions were equivalent to a fluence of approximately 1 or 2 particle traversals per nucleus. In most cases, Aprt mutant frequencies in the irradiated mice were not significantly increased relative to the controls for any of the particles or doses tested at the pre-determined harvest time (3–5 months after irradiation). Despite the lack of increased Aprt mutant frequencies in the irradiated splenocytes, a molecular analysis centered on chromosome 8 revealed the induction of radiation signature mutations (large interstitial deletions and complex mutational patterns), with the highest levels of induction at 2 particles nucleus for the {sup 48}Ti and {sup 56}Fe ions. In total, the results show that densely ionizing HZE ions can induce characteristic mutations in splenic T cells at low fluence, and that at least a subset of radiation-induced mutant cells are stably retained despite the apparent lack of increased mutant frequencies at the time of harvest.

Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

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Wu Kong-Yan

2010-06-01

Full Text Available Abstract Background During cerebellar development, Purkinje cells (PCs form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. Results We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML, the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. Conclusion Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.

Cell Type Preference of a Novel Human Derived Cell-Permeable Peptide dNP2 and TAT in Murine Splenic Immune Cells.

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Sangho Lim

Full Text Available Cell-permeable peptides (CPPs have been widely studied as an attractive drug delivery system to deliver therapeutic macromolecules such as DNA, RNA, and protein into cells. However, its clinical application is still limited and controversial due to the lack of a complete understanding of delivery efficiency in target cells. Previously we identified and characterized the novel and superior CPP, named dNP2, and here we comparatively analyzed intracellular delivery efficiency of dNP2 and TAT in various immune cells of mouse spleen to demonstrate their cell type preference. dNP2- or TAT-conjugated fluorescent proteins were most efficiently taken up by phagocytic cells such as dendritic cells and macrophages while little protein uptake was seen by lymphocytes including T cells, B cells, and NK cells. Interestingly CD8+ lymphoid dendritic cells and CD62LloCD44hi memory like T cell subsets showed significantly better uptake efficiency in vitro and in vivo relative to other dendritic cells or T cells, respectively. In addition, activated macrophages, T cells, and B cells took up the proteins more efficiently relative to when in the resting state. Importantly, only dNP2, not TAT, shows significant intracellular protein delivery efficiency in vivo. Collectively, this study provides important information regarding heterogeneous intracellular delivery efficiency of CPPs such as dNP2 and TAT with cell type preference in the spleen needed for its application in phagocytic cells or activated immune cells.

Large-Scale mRNA Transfection of Dendritic Cells by Electroporation in Continuous Flow Systems

DEFF Research Database (Denmark)

Selmeczi, Dávid; Hansen, Thomas Steen; Met, Özcan

2016-01-01

with high cell survival. Continuous flow of suspended dendritic cells through a channel incorporating spatially separated microporous meshes with a synchronized electrical pulsing sequence can yield dendritic cell transfection rates of >75 % with survival rates of >90 %. This chapter describes...

Targeting nanoparticles to dendritic cells for immunotherapy.

NARCIS (Netherlands)

Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

2012-01-01

Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells.

Science.gov (United States)

Hausselt, Susanne E; Euler, Thomas; Detwiler, Peter B; Denk, Winfried

2007-07-01

Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs) playing a major role. SACs generate larger dendritic Ca(2+) signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS) in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca(2+)] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage-activated Ca(2+) channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination.

A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells.

Directory of Open Access Journals (Sweden)

Susanne E Hausselt

2007-07-01

Full Text Available Detection of image motion direction begins in the retina, with starburst amacrine cells (SACs playing a major role. SACs generate larger dendritic Ca(2+ signals when motion is from their somata towards their dendritic tips than for motion in the opposite direction. To study the mechanisms underlying the computation of direction selectivity (DS in SAC dendrites, electrical responses to expanding and contracting circular wave visual stimuli were measured via somatic whole-cell recordings and quantified using Fourier analysis. Fundamental and, especially, harmonic frequency components were larger for expanding stimuli. This DS persists in the presence of GABA and glycine receptor antagonists, suggesting that inhibitory network interactions are not essential. The presence of harmonics indicates nonlinearity, which, as the relationship between harmonic amplitudes and holding potential indicates, is likely due to the activation of voltage-gated channels. [Ca(2+] changes in SAC dendrites evoked by voltage steps and monitored by two-photon microscopy suggest that the distal dendrite is tonically depolarized relative to the soma, due in part to resting currents mediated by tonic glutamatergic synaptic input, and that high-voltage-activated Ca(2+ channels are active at rest. Supported by compartmental modeling, we conclude that dendritic DS in SACs can be computed by the dendrites themselves, relying on voltage-gated channels and a dendritic voltage gradient, which provides the spatial asymmetry necessary for direction discrimination.

Dendritic cells support production of IgA and other non-IgM isotypes in clonal microculture.

Science.gov (United States)

Schrader, C E; George, A; Kerlin, R L; Cebra, J J

1990-01-01

Microcultures of helper T (Th) cells and a few appropriately primed murine B cells can be used to detect cognate T-B interactions which lead to clonal production of IgM, IgG1, and IgE. However, IgG2, IgG3, and IgA are very rarely expressed. We have found that the addition of dendritic cells to such cultures creates an extremely supportive environment for clones expressing IgA with other isotypes, as well as clones expressing only detectable IgA. Typically, 400 dendritic cells were added to 3000 conalbumin-specific Th cells (D10.G4.1) and 30 hapten-specific Peyer's patch (PP) B cells with antigen in 15 microliters. The response was antigen dependent and clonal. Almost half of the clones expressed only non-IgM isotypes, 43% expressed some IgA, and 14% expressed some IgG3; isotype diversity increased over time. Dendritic cells from PP and spleen were found to be equally supportive, and allowed the number of T cells required in microculture to be decreased from 3000 to 400. However, T cell proliferation was not required for the supportive effect of dendritic cells. Surface IgD-bearing cells were also found to switch to IgA production in microculture as judged by their generating clones expressing IgM along with IgA and other isotypes. Again, IgA was usually expressed only in the presence of dendritic cells. The mechanism may involve dendritic cell-induced T cell activation and/or dendritic cell factors, and is under investigation.

Modulation of Dendritic Cell Responses by Parasites: A Common Strategy to Survive

Directory of Open Access Journals (Sweden)

César A. Terrazas

2010-01-01

Full Text Available Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved.

Dendritic cell fate is determined by BCL11A

Science.gov (United States)

Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

2014-01-01

The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

Directory of Open Access Journals (Sweden)

Kathleen Marie Kokolus

2014-02-01

Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

Polysaccharide purified from Ganoderma atrum induced activation and maturation of murine myeloid-derived dendritic cells.

Science.gov (United States)

Wang, Hui; Yu, Qiang; Nie, Shao-Ping; Xiang, Quan-Dan; Zhao, Ming-Ming; Liu, Shi-Yu; Xie, Ming-Yong; Wang, Shun-Qi

2017-10-01

Ganoderma atrum (G. atrum), a member of the genus Ganoderma, is an edible and medicinal fungus. In this study, we investigated the direct and indirect effects of G. atrum polysaccharide (PSG-1) on dendritic cells (DCs). Firstly, flow cytometric and ELISA analysis showed that PSG-1 increased cell surface molecule expression of MHC-II, CD80 and CD86, and enhanced the production of IL-12 p70, IL-6, IL-10, RANTES, MIP-1α and MCP-1 in DCs. PSG-1-treated DCs promoted the proliferation of splenic T lymphocyte of mouse in mixed lymphocyte reaction. The above results demonstrated that PSG-1 induced the maturation of DCs. Secondly, PSG-1 increased the phosphorylation of p38, ERK and JNK determined by western blot. Inhibitors of p38, ERK and JNK decreased PSG-1-induced expression of MHC-II, CD80 and CD86 and production of IL-6 and IL-10 by DCs. These results suggested that PSG-1 induced mitogen-activated protein kinase (MAPK) activation was involved in the regulation of maturation markers and cytokines expression in DCs. Finally, PSG-1 increased expression of MHC-II of DCs in a DCs-Caco-2 co-culture model, suggesting that PSG-1 could indirectly influence DCs. In summary, our data suggested that PSG-1 directly induced DCs maturation via activating MAPK pathways, and indirectly stimulated DCs separated by intestinal epithelial cells. Copyright © 2017. Published by Elsevier Ltd.

Insulin radioreceptor assay on murine splenic leukocytes and peripheral erythrocytes

International Nuclear Information System (INIS)

Shimizu, F.; Kahn, R.

1982-01-01

Insulin radioreceptor assays were developed using splenic leukocytes and peripheral erythrocytes from individual mice. Splenic leukocytes were prepared using an NH 4 Cl buffer which did not alter insulin binding, but gave much higher yields than density gradient methods. Mouse erythrocytes were isolated from heparinized blood by three passages over a Boyum gradient, and a similar buffer was used to separate cells from free [ 125 I]iodoinsulin at the end of the binding incubation. Insulin binding to both splenic leukocytes and peripheral erythrocytes had typical pH, temperature, and time dependencies, and increased linearly with an increased number of cells. Optimal conditions for the splenic leukocytes (6 x 10 7 /ml) consisted of incubation with [ 125 I]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.0. In cells from 20 individual mice, the specific [ 125 I]iodoinsulin binding was 2.6 +/- 0.1% (SEM), and nonspecific binding was 0.3 +/- 0.04% (10.6% of total binding). Erythrocytes (2.8 x 10 9 /ml) were incubated with [ 125 ]iodoinsulin at 15 C for 2 h in Hepes buffer, pH 8.2. In cells from 25 individual mice, the specific [ 125 I]iodoinsulin binding was 4.5 +/- 0.2%, and nonspecific binding was 0.7 +/- 0.03% (13.6% of total binding). In both splenic leukocytes and peripheral erythrocytes, analysis of equilibrium binding data produced curvilinear Scatchard plots with approximately 3500 binding sites/leukocyte and 20 binding sites/erythrocyte. These data demonstrate that adequate numbers of splenic leukocytes and peripheral erythrocytes can be obtained from individual mice to study insulin binding in a precise and reproducible manner

CT of splenic trauma

International Nuclear Information System (INIS)

Griffiths, B.G.; Federle, M.P.; Minagi, H.; Jeffrey, R.B.

1986-01-01

Fifty-five consecutive cases of surgically proved splenic injuries were evaluated by CT. CT correctly identified 54 splenic injuries, with one false-negative and three false-positive studies. In the single false-negative study and in two of the three false-positive studies, CT correctly indicated the presence of a large hemoperitoneum and other abdominal visceral lacerations and so correctly indicated the need for surgery. Of the 55 proved cases of splenic injury, CT revealed hemoperitoneum in 54 (99%), perisplenic clot in 47 (85%), splenic laceration in 39 (71%), and subcapsular hematoma in 13 (24%). Perisplenic clot can be distinguished from lysed blood in the peritoneal cavity and is a sensitive and specific sign of splenic trauma, even in the absence of visible splenic laceration. The authors conclude that CT is highly reliable means of evaluating splenic trauma

Commensal oral bacteria antigens prime human dendritic cells to induce Th1, Th2 or Treg differentiation.

Science.gov (United States)

Kopitar, A N; Ihan Hren, N; Ihan, A

2006-02-01

In various immunopathologic conditions, bacterial flora induce an immune response which results in inflammatory manifestations, e.g. periapical granuloma. Dendritic cells provide the main orchestration of specific immune responses. The aim of our study was to test the capacity of distinct oral bacterial antigens (prepared from Streptococcus mitis, Propionibacterium acnes, and Bacteroides spp.) to prime human dendritic cells for stimulation of the T-lymphocyte response. To assess the T-lymphocyte response, the expression of CD25, CD69, intracellular interferon gamma (cIFN-gamma), and intracellular interleukin 4 (cIL-4) was determined. Dendritic cells were prepared from leukocyte buffy coat from healthy blood donors. Monocytes were stimulated with IL-4 and GM-CSF and dendritic cells activated with bacterial lysates. Cell suspensions contained up to 90% dendritic cells, which represented 2-12% of the initial number of mononuclear cells. Lymphocyte subsets that developed in lymphocyte cultures after 1 week of stimulation were analyzed by flow cytometry. Dendritic cells, primed with antigens of Bacteroides fragilis have shown significantly higher activation and expression of intercellular IFN-gamma by T lymphocytes compared to negative controls. The dendritic cells primed with antigens of P. acnes had no effect on T-lymphocyte activation or cytokine production; instead they induced differentiation of T lymphocytes into CD25bright cells (regulatory T cells) with a potentially inhibitory effect on immune response. Dendritic cells primed with antigens of S. mitis induced increased expression of cIL-4. We conclude that commensal oral bacteria antigens prepared from B. fragilis, S. mitis, and P. acnes prime human dendritic cells to induce Th1, Th2, and T(reg) differentiation, respectively. This may advance our understanding of immunopathologic manifestations in the oral cavity and offer new possibilities for redirecting immune responses in mucosal vaccination.

DMPD: Proximal effects of Toll-like receptor activation in dendritic cells. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17142025 Proximal effects of Toll-like receptor activation in dendritic cells. Watt...) (.svg) (.html) (.csml) Show Proximal effects of Toll-like receptor activation in dendritic cells. PubmedID... 17142025 Title Proximal effects of Toll-like receptor activation in dendritic ce

Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy

Directory of Open Access Journals (Sweden)

Sabine eKuhn

2015-11-01

Full Text Available Tumors harbor several populations of dendritic cells with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor site can activate anti-tumor immune responses, and is associated with the appearance of a population of monocyte-derived dendritic cells in the tumor and tumor-draining lymph node. Here we use dendritic cell or monocyte depletion and monocyte transfer to show that these monocyte-derived dendritic cells are critical to the activation of anti-tumor immune responses. Treatment with the immunostimulatory agents Monosodium Urate crystals and Mycobacterium smegmatis induced the accumulation of monocytes in the draining lymph node, their upregulation of CD11c and MHCII, and expression of iNOS, TNFα and IL12p40. Blocking monocyte entry into the lymph node and tumor through neutralization of the chemokine CCL2 or inhibition of Colony Stimulating Factor-1 receptor signaling prevented the generation of monocyte-derived dendritic cells, the infiltration of tumor-specific T cells into the tumor, and anti-tumor responses. In a reciprocal fashion, monocytes transferred into mice depleted of CD11c+ cells were sufficient to rescue CD8+ T cell priming in lymph node and delay tumor growth. Thus monocytes exposed to the appropriate conditions become powerful activators of tumor-specific CD8+ T cells and anti-tumor immunity.

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling.

Science.gov (United States)

Arribas, Alberto J; Gómez-Abad, Cristina; Sánchez-Beato, Margarita; Martinez, Nerea; Dilisio, Lorena; Casado, Felipe; Cruz, Miguel A; Algara, Patrocinio; Piris, Miguel A; Mollejo, Manuela

2013-07-01

Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

Full restoration of Brucella-infected dendritic cell functionality through Vγ9Vδ2 T helper type 1 crosstalk.

Directory of Open Access Journals (Sweden)

Ming Ni

Full Text Available Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate Vγ9Vδ2 T cells through contact-dependent mechanisms, 2/activated Vγ9Vδ2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated Vγ9Vδ2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated Vγ9Vδ2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies.

Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

KAUST Repository

Zibellini, S.

2010-05-29

Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin\\'s lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

KAUST Repository

Zibellini, S.; Capello, D.; Forconi, F.; Marcatili, P.; Rossi, D.; Rattotti, S.; Franceschetti, S.; Sozzi, E.; Cencini, E.; Marasca, R.; Baldini, L.; Tucci, A.; Bertoni, F.; Passamonti, F.; Orlandi, E.; Varettoni, M.; Merli, M.; Rizzi, S.; Gattei, V.; Tramontano, A.; Paulli, M.; Gaidano, G.; Arcaini, L.

2010-01-01

Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin's lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells

Directory of Open Access Journals (Sweden)

Afsson shariat

2015-11-01

Full Text Available Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Blood samples were taken from 5 healthy volunteers. Following the generation of monocyte-derived dendritic cells on the fifth day of cell culture, half of the immature dendritic cells were treated with cytomegalovirus glycoprotein B, and the rest of them were induced to mature dendritic untreated cells and were used as the control group. The maturation and function of dendritic cells were evaluated in these two groups. Results: The gene expression level of toll-like receptor-4 significantly increased in the group treated with glycoprotein B (p < 0.05, whereas there were no significant differences in the expression rates of CD83, CD86, CD1a, and HLA-DR and the secretion of IL-23 from monocyte-derived dendritic cells between the treated groups and the controls. Conclusion: The increase in the gene expression of toll-like receptor-4 in monocyte-derived dendritic cells treated with cytomegalovirus glycoprotein B showed that cell contact is required to elicit cellular antiviral response and toll-like receptor activation. Thus, it is critical to recognize the viral and cellular determinants of the immune system in order to develop new therapeutic strategies against cytomegalovirus.

Evaluation of two different dendritic cell preparations with BCG reactivity

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Fol Marek

2016-01-01

Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

Activation-induced cell death of dendritic cells is dependent on sphingosine kinase 1

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Anja eSchwiebs

2016-04-01

Full Text Available Sphingosine 1-phosphate (S1P is an immune modulatory lipid mediator and has been implicated in numerous pathophysiological processes. S1P is produced by sphingosine kinase 1 (Sphk1 and Sphk2. Dendritic cells (DCs are central for the direction of immune responses and crucially involved in autoimmunity and cancerogenesis. In this study we examined the function and survival of bone marrow-derived DCs under long-term inflammatory stimulation. We observed that differentiated cells undergo activation-induced cell death upon LPS stimulation with an increased metabolic activity shortly after stimulation, followed by a rapid activation of caspase 3 and subsequent augmented apoptosis. Importantly, we highlight a profound role of Sphk1 in secretion of inflammatory cytokines and survival of dendritic cells that might be mediated by a change in sphingolipid levels as well as by a change in STAT3 expression. Cell growth during differentiation of Sphk1-deficient cells treated with the functional S1P receptor antagonist FTYP was reduced. Importantly, in dendritic cells we did not observe a compensatory regulation of Sphk2 mRNA in Sphk1-deficient cells. Instead, we discovered a massive increase in Sphk1 mRNA concentration upon long-term stimulation with LPS in wild type cells that might function as an attempt to rescue from inflammation-caused cell death. Taken together, in this investigation we describe details of a crucial involvement of sphingolipids and Sphk1 in activation-induced cell death during long-term immunogenic activity of DCs that might play an important role in autoimmunity and might explain the differences in immune response observed in in vivo studies of Sphk1 modulation.

Bulk protein biosynthesis of the spleen and some splenic cell populations after induction of splenomegaly by application of Bordetella pertussis

International Nuclear Information System (INIS)

Krammenschneider, D.

1980-01-01

Autoradiographic studies and liquid scintillation counting were carried out in female NMRI mice just reaching maturity. All animals had received a single injection, either of bovine serum albumin (BSA) or of pertussis organism (PO) or BSA + PO. The animals were sacrificed 4 d and 10 d after this pretreatment. 2 h before decapitation, a single dose of 3 H-l phenyl alamine was applied intraperitoneally. The following results were obtained: The splenic index (splenic weight in mg/mouse weight in g) increased as a result of splenomegaly caused by PO. Morphometric data suggested an enlarged cell and nuclear area with enhanced cellular amino acid turnover and migration of RNP-containing matter into the nucleus, especially in the megakaryocytes and in lymphocytoid blastic cells. Incorporation of 3 H-l-phenylalanine per unit of dry weight of the spleen is slowed down during the experiment while amiro acid incorporation by the total spleen increases with PO-induced splenomegaly. Incorporation of amino acid per unit of dry weight is constant in all experimental and control animals. The increased amino acid incorporation in lymphocytoid blastic cells is probably caused by the immunological situations during the experiment. An explanation of total cell increase and cell increase of megakaryocytic splenic cells is attempted. (orig./MG) [de

Identification of human tissue cross-presenting dendritic cells

OpenAIRE

Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

2013-01-01

Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

Science.gov (United States)

Zhang, Bin; Liu, Rui; Shi, Dan; Liu, Xingxia; Chen, Yuan; Dou, Xiaowei; Zhu, Xishan; Lu, Chunhua; Liang, Wei; Liao, Lianming; Zenke, Martin; Zhao, Robert C H

2009-01-01

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

The effects of renal transplantation on circulating dendritic cells

NARCIS (Netherlands)

D.A. Hesselink (Dennis); L.M.B. Vaessen (Leonard); W.C.J. Hop (Wim); W. Schoordijk-Verschoor (Wenda); J.N.M. IJzermans (Jan); C.C. Baan (Carla); W. Weimar (Willem)

2005-01-01

textabstractThe effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in

Unimpaired dendritic cell functions in MVP/LRP knockout mice.

NARCIS (Netherlands)

Mossink, MH; Groot, de J.; Zon, van A; Franzel-Luiten, E; Schoester, M.; Scheffer, G.L.; Sonneveld, P.; Scheper, R.J.; Wiemer, EA

2003-01-01

Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

International Nuclear Information System (INIS)

Gratwohl, A.; Hermans, J.; Biezen, A.V.

1996-01-01

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

Use of radionuclide techniques for assessment of splenic function and detection of splenic remnants

International Nuclear Information System (INIS)

Ganguly, S.; Sinha, S.; Sarkar, B.R.; Basu, S.; Ghosh, S.

1998-01-01

Full text: The spleen is often involved in hematological malignancies; it is also the site of RBC destruction in thalassemia and ITP. In latter cases, splenectomy is often performed and postoperatively, detection of functioning splenic remnants affect the prognosis adversely. In this study, we assessed the usefulness of radionuclide techniques in : a) assessment of splenic function in primarily non-splenic diseases (benign or malignant), and b) detection of splenic remnant after splenectomy. 12 patients of splenomegaly and 5 patients after splenectomy underwent splenic imaging; imaging was performed using both 99m Tc-sulphur colloid (with first pass) and 99m Tc labelled heat denatured RBCs as tracers. Thus splenic perfusion, morphology and RBC trapping functions were all assessed. The colloid images usually matched the RBC images except in 2 cases where photogenic areas (presumably infarcts) were visualized on RBC scans that were missed on colloid scans. Three of the post splenectomy cases revealed functioning splenic remnants, which was also better visualized on RBC scans. It is concluded that radionuclide imaging could be used regularly for assessing function of spleen, or detecting splenic remnants

Thy-1+ dendritic cells in murine epidermis are bone marrow-derived

International Nuclear Information System (INIS)

Breathnach, S.M.; Katz, S.I.

1984-01-01

Thy-1+, Ly-5+ dendritic cells have recently been described as a resident cell population in murine epidermis, but their ontogeny and function are unknown. The origin and turnover of epidermal Thy-1+ cells utilizing chimeric mice were investigated. Lethally x-irradiated AKR/J (Thy-1.1+) and AKR/Cum (Thy-1.2+) mice were reconstituted with allogeneic bone marrow cells with or without thymocytes from congenic AKR/Cum or AKR/J mice, respectively. The density of residual indigenous Thy-1.1+ cells in AKR/J chimeras and Thy-1.2+ cells in AKR/Cum chimeras was substantially reduced following x-irradiation, as determined by immunofluorescence staining of epidermal sheets. Epidermal repopulation by allogeneic Thy-1+ dendritic epidermal cells was first observed at 5 weeks in AKR/J chimeras and at 7 weeks in AKR/Cum chimeras and progressed slowly. Repopulation was not enhanced by increasing the number of allogeneic bone marrow cells injected from 2 X 10(7) to 10(8) cells or by the addition of 8 X 10(7) allogeneic thymocytes to the donor inoculate. Epidermal repopulation by allogeneic Thy-1.2+ cells was not seen in AKR/J mice reconstituted with syngeneic bone marrow cells and allogeneic Thy-1.2+ AKR/Cum thymocytes. Taken together, these results indicate that Thy-1+ dendritic epidermal cells are derived from the bone marrow and suggest that they are not related to conventional peripheral T-lymphocytes

Evaluation of accessory cell heterogeneity. III. Role of dendritic cells in the in vitro activation of the antibody response to soluble antigens.

Science.gov (United States)

Erb, P; Ramila, G; Sklenar, I; Kennedy, M; Sunshine, G H

1985-05-01

Dendritic cells and macrophages obtained from spleen and peritoneal exudate were tested as accessory cells for the activation of lymphokine production by T cells, for supporting T-B cooperation and for the induction of antigen-specific T helper cells. Dendritic cells as well as macrophages were able to activate T cells for interleukin-2 secretion and functioned as accessory cells in T-B cooperation, but only macrophages induced T helper cells, which cooperate with B cells by a linked recognition interaction, to soluble antigens. Dendritic cell- and antigen-activated T cells also did not help B cells in the presence of Con A supernatants which contained various T cell- and B cell-stimulatory factors. The failure of dendritic cells to differentiate memory into functional T helper cells, but their efficient accessory cell function in T-B cooperation, where functional T helper cells are already present, can be best explained by a differential accessory cell requirement for T helper cell activation dependent on the differentiation stage of the T helper cell.

[Saccharomyces boulardii modulates dendritic cell properties and intestinal microbiota disruption after antibiotic treatment].

Science.gov (United States)

Collignon, A; Sandré, C; Barc, M-C

2010-09-01

Saccharomyces boulardii is a non-pathogenic yeast with biotherapeutic properties that has been used successfully to prevent and to treat various infectious and antibiotic-associated diarrheas. The intestinal microbiota is responsible for colonization resistance and immune response to pathogens but can be disrupted by antibiotics and lose its barrier effect. Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to initiate a primary immune response or immune tolerance. In a human microbiota-associated mouse model, we evaluated the influence of S. boulardii on the composition of the microbiota and on the properties of dendritic cells in normal homeostatic conditions and after antibiotic-induced stress. The DCs were derived from splenic precursors. Membrane antigen expression and phagocytosis of FITC-latex beads by DCs were evaluated by flow cytometry. The molecular analysis of the microbiota was performed with fluorescence in situ hybridization (FISH) combined with flow cytometry or confocal microscopy using group specific 16S rRNA targeted probes. This evaluation was conducted during and after a 7-day oral treatment with amoxicillin-clavulanic acid alone and in combination with the administration of the yeast. The antibiotic treatment increased the phagocytic activity of DCs. Their antigen presenting function (MHC class II antigen and CD 86 costimulatory molecule membrane expression) was up-regulated. This reflects a functional activation of DCs. In the presence of S. boulardii, the modification of membrane antigen expression was down regulated. To correlate these modifications to the microbiota disruption, we analyzed in parallel the composition of the intestinal microbiota. As previously shown, the amoxicillin-clavulanic acid treatment, both alone and with S. boulardii, did not quantitatively alter the total microbiota. In contrast, after one day of the antibiotic treatment the Clostridium coccoides group decreased

Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+ dendritic cells.

Science.gov (United States)

Parekh, Vrajesh V; Pabbisetty, Sudheer K; Wu, Lan; Sebzda, Eric; Martinez, Jennifer; Zhang, Jianhua; Van Kaer, Luc

2017-08-01

The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34 -deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways. Surprisingly, these animals displayed a defect in the homeostatic maintenance of splenic CD8α + DCs and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor. Importantly, mice deficient in the Vps34-associated protein Rubicon, which is critical for a noncanonical form of autophagy called "Light-chain 3 (LC3)-associated phagocytosis" (LAP), lacked such defects. Finally, consistent with their defect in the cross-presentation of apoptotic cells, DC-specific Vps34 -deficient animals developed increased metastases in response to challenge with B16 melanoma cells. Collectively, our studies have revealed a critical role of Vps34 in the regulation of CD8α + DC homeostasis and in the capacity of these cells to process and present antigens associated with apoptotic cells to MHC class I-restricted T cells. Our findings also have important implications for the development of small-molecule inhibitors of Vps34 for therapeutic purposes.

Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

Science.gov (United States)

Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

2014-01-01

Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

Science.gov (United States)

Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

1999-03-01

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

CD56 marks human dendritic cell subsets with cytotoxic potential

NARCIS (Netherlands)

Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

2013-01-01

Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56(+) DCs are endowed with an unconventional cytotoxic capacity.

Blastic plasmacytoid dendritic cell neoplasm: report of two pediatric cases.

Science.gov (United States)

Dharmani, Preeti Ashok; Mittal, Neha Manish; Subramanian, P G; Galani, Komal; Badrinath, Yajamanam; Amare, Pratibha; Gujral, Sumeet

2015-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of acute leukemia that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited. We report cases of two children in whom bone marrow showed infiltration by large atypical monocytoid 'blast-like' cells which on immunophenotyping expressed CD4, CD56, HLA-DR and CD33 while were negative for CD34 other T-cell, B-cell and myeloid markers. The differential diagnoses considered were AML, T/NK-cell leukemia and acute undifferentiated leukemia. Additional markers CD303/BDCA-2 and CD123 which are recently validated plasmacytoid dendritic cell markers were done which helped us clinch the diagnosis of this rare neoplasm. An accurate diagnosis of BPDCN is essential in order to provide prompt treatment. Due to its rarity and only recent recognition as a distinct clinicopathological entity, no standardized therapeutic approach has been established for BPDCN.

Harnessing Dendritic Cells for Tumor Antigen Presentation

Energy Technology Data Exchange (ETDEWEB)

Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

2011-04-26

Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

Antibody response to a T-cell-independent antigen is preserved after splenic artery embolization for trauma

NARCIS (Netherlands)

Olthof, D. C.; Lammers, A. J. J.; van Leeuwen, E. M. M.; Hoekstra, J. B. L.; ten Berge, I. J. M.; Goslings, J. C.

2014-01-01

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function

Dendritic cell-associated immune inflammation of cardiac mucosa: a possible factor in the formation of Barrett's esophagus.

Science.gov (United States)

Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-03-01

The development of Barrett's esophagus is poorly understood, but it has been suggested that cardiac mucosa is a precursor of intestinal type metaplasia and that inflammation of cardiac mucosa may play a role in the formation of Barrett's esophagus. The present study was undertaken to examine the presence and distribution of immune-inflammatory cells in cardiac mucosa, specifically focusing on dendritic cells because of their importance as regulators of immune reactions. Endoscopic biopsy specimens were obtained from 12 patients with cardiac mucosa without Barrett's esophagus or adenocarcinoma and from 21 patients with Barrett's esophagus without dysplasia (intestinal metaplasia). According to histology, in nine of the 21 specimens with Barrett's esophagus, areas of mucosa composed of cardiac type epithelium-lined glands were present as well. Immunohistochemical staining and electron microscopy were used to examine immune-inflammatory cells in paraffin-embedded sections. Immune-inflammatory cells, including T cells, B cells, dendritic cells, macrophages, and mast cells, were present in the connective tissue matrix that surrounded cardiac type epithelium-lined glands in all patients with cardiac mucosa. Clustering of dendritic cells with each other and with lymphocytes and the intrusion of dendritic cells between glandular mucus cells were observed. In the Barrett's esophagus specimens that contained cardiac type glands, computerized CD83 expression quantitation revealed that there were more dendritic cells in cardiac mucosa than in intestinal metaplasia. Immune-inflammatory infiltrates containing dendritic cells are consistently present in cardiac mucosa. The finding of a larger number of dendritic cells in areas of cardiac mucosa in Barrett's esophagus biopsies suggests that the immune inflammation of cardiac mucosa might play a role in modifying the local tissue environment to promote the development of specialized intestinal type metaplasia.

Multiple splenic abscesses

Directory of Open Access Journals (Sweden)

Harish Kumar

2015-01-01

Full Text Available Splenic abscess is a rare clinical entity with poor prognosis. But owing to imaging technique, diagnosis and prognosis have improved nowadays. Most patients who are presented with splenic abscess are immunocompromised due to predisposing risk factors like diabetes mellitus, intravenous drug abuse, trauma, bacterial endocarditis, human immunodeficiency virus (HIV, chemotherapy, or steroids. Here, we are presenting a rarer case of multiple splenic abscesses with its complication in an immunocompetent healthy adult male without any risk factor.

Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

DEFF Research Database (Denmark)

Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

2002-01-01

recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

Exploiting the role of endogenous lymphoid-resident dendritic cells in the priming of NKT cells and CD8+ T cells to dendritic cell-based vaccines.

Directory of Open Access Journals (Sweden)

Troels R Petersen

2011-03-01

Full Text Available Transfer of antigen between antigen-presenting cells (APCs is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs, were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs, suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT cells. In fact, injection of α-GalCer-loaded CD1d-/- BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose.

Antibody response to a T-cell-independent antigen is preserved after splenic artery embolization for trauma.

Science.gov (United States)

Olthof, D C; Lammers, A J J; van Leeuwen, E M M; Hoekstra, J B L; ten Berge, I J M; Goslings, J C

2014-11-01

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Intrasplenic masses of ``preserved`` functioning splenic tissue in sickle cell disease: correlation of imaging findings (CT, ultrasound, MRI, and nuclear scintigraphy)

Energy Technology Data Exchange (ETDEWEB)

Levin, T.L. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Berdon, W.E. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Haller, J.O. [Department of Radiology, SUNY Downstate Medical Center, Brooklyn, New York (United States); Ruzal-Shapiro, C. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Hurlet-Jenson, A. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, New York (United States)

1996-09-01

Purpose. We studied six patients with sickle cell disease (SSD), five homozygous for sickle cell anemia and one with sickle beta-thalassemia, in whom rounded intrasplenic masses proved to be preserved functioning splenic tissue. Materials and methods. Available images including computed tomography, ultrasonography, bone scans (Tc-99m MDP), liver spleen scans (Tc-99m sulfur colloid), and MRI were evaluated. Results. The masses were low density on CT (in an otherwise calcified spleen), hypoechoic relative to the echogenic spleen on US, and had the imaging characteristics of normal spleen on MRI. They failed to accumulate Tc-99m MDP but did demonstrate uptake of Tc-99m sulfur colloid. Conclusion. In a patient with SSD and intrasplenic masses, proper correlation of multiple imaging modalities will establish the diagnosis of functioning splenic tissue and avoid mistaken diagnosis of splenic abscess or infarction. (orig.). With 2 figs., 1 tab.

Intrasplenic masses of ''preserved'' functioning splenic tissue in sickle cell disease: correlation of imaging findings (CT, ultrasound, MRI, and nuclear scintigraphy)

International Nuclear Information System (INIS)

Levin, T.L.; Berdon, W.E.; Haller, J.O.; Ruzal-Shapiro, C.; Hurlet-Jenson, A.

1996-01-01

Purpose. We studied six patients with sickle cell disease (SSD), five homozygous for sickle cell anemia and one with sickle beta-thalassemia, in whom rounded intrasplenic masses proved to be preserved functioning splenic tissue. Materials and methods. Available images including computed tomography, ultrasonography, bone scans (Tc-99m MDP), liver spleen scans (Tc-99m sulfur colloid), and MRI were evaluated. Results. The masses were low density on CT (in an otherwise calcified spleen), hypoechoic relative to the echogenic spleen on US, and had the imaging characteristics of normal spleen on MRI. They failed to accumulate Tc-99m MDP but did demonstrate uptake of Tc-99m sulfur colloid. Conclusion. In a patient with SSD and intrasplenic masses, proper correlation of multiple imaging modalities will establish the diagnosis of functioning splenic tissue and avoid mistaken diagnosis of splenic abscess or infarction. (orig.). With 2 figs., 1 tab

The splenomegaly of myeloproliferative and lymphoproliferative disorders: splenic cellularity and vascularity

Energy Technology Data Exchange (ETDEWEB)

Zhang, B (Capital Hospital, Peking University Medical College, Beijing (China)); Lewis, S.M. (Department of Haematology, Royal Postgraduate Medical School, London (UK))

1989-01-01

Employing radionuclide scanning, the volume of the spleen, its red cell pool and plasma pool have been measured in vivo, and the relative proportions of cellularity and vascularity of the spleen have been calcualted in 51 patients with myeloproliferactive and lymphoproliferative disorders. In primary proliferative polycythaemia (polycythaemia vera), the increase of spleen size was attributed mainly to the increase of splenic vascularity; in myelofibrosis and in hairy cell leukaemia, the increase of spleen size was associated with increase in both splenic vascularity and cellularity, whilst in size was associated with increase in both splenic vascularity and cellularity, whilst in CGL and CLL the increase was attributed more to cellularity than to vascularity. (author).

Difficult preoperative diagnosis of a patient with sclerosing splenic hemangioma

International Nuclear Information System (INIS)

Edoute, Y.; Ben-Haim, S.A.; Ben-Arie, Y.; Fishman, A.; Barzilai, D.

1989-01-01

We present a young asymptomatic woman with splenomegaly and a large isolated splenic mass demonstrated by ultrasonography, 99m Tc sulfur colloid, and gallium scintigraphy studies. Computerized tomography (CT) and three-phase 99mTc-labeled red blood cell imaging suggested a malignant lesion. Repeated sonographically guided fine needle aspiration (FNA) obtained only blood, suggesting the possible vascular nature of the tumor. Splenectomy established the diagnosis of splenic hemangioma (SH) with marked sclerotic changes. We conclude from this case that (1) the sclerotic and cystic changes in the SH and the abdominal lymphadenopathy could explain why the three-phase red blood cell and CT scanning, respectively, suggested that the lesion was malignant rather than benign; (2) guided FNA of a splenic mass suspected to be hemangioma may be an additional safe and useful diagnostic procedure. Multiple aspirations yielding blood alone suggest hemangioma and may prevent an unnecessary operation. To the best of our knowledge, this is the first reported case in the literature of FNA of splenic hemangioma

Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses.

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Sandra J van Vliet

2009-10-01

Full Text Available Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS molecule correlates with altered disease states. Here, we investigated the interaction of different stable gonoccocal LOS phenotypes with human dendritic cells and demonstrate that each variant targets a different set of receptors on the dendritic cell, including the C-type lectins MGL and DC-SIGN. Neisseria gonorrhoeae LOS phenotype C constitutes the first bacterial ligand to be described for the human C-type lectin receptor MGL. Both MGL and DC-SIGN are locally expressed at the male and female genital area, the primary site of N. gonorrhoeae infection. We show that targeting of different C-type lectins with the N. gonorrhoeae LOS variants results in alterations in dendritic cell cytokine secretion profiles and the induction of distinct adaptive CD4(+ T helper responses. Whereas N. gonorrhoeae variant A with a terminal N-acetylglucosamine on its LOS was recognized by DC-SIGN and induced significantly more IL-10 production, phenotype C, carrying a terminal N-acetylgalactosamine, primarily interacted with MGL and skewed immunity towards the T helper 2 lineage. Together, our results indicate that N. gonorrhoeae LOS variation allows for selective manipulation of dendritic cell function, thereby shifting subsequent immune responses in favor of bacterial survival.

Human antibodies to dendritic cells : generation, analysis and use in vaccination

NARCIS (Netherlands)

Lekkerkerker, A.N.

2002-01-01

Dendritic cells (DCs) are widely recognized as professional antigen presenting cells (APCs) that play a pivotal role in directing the immune response. DCs are a heterogeneous cell population that continuously derive from bone marrow cells and reside as sentinels in an immature stage in the

Embolisation of the splenic artery

Energy Technology Data Exchange (ETDEWEB)

Essler, G; Duex, A

1982-09-01

In bleeding of oesophageal varices with resistance to common treatment embolisation of the splenic artery causes depression of the portal hypertension by forty per cent. Thrombosis of the splenic or portal vein as in splenectomies are not to be expected. The splenic vein remains open for later spleno-renal anastomosis. By occlusion of the splenic artery we were successful in stopping oesophageal bleeding. In a patient with dominant hypersplenism in portal hypertension the severity of the syndrome decreased after embolisation of the splenic artery. Thrombocytes, leukocytes and gammaglobulin increased.

The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis.

Science.gov (United States)

Pizzi, Marco; Gergis, Usama; Chaviano, Felicia; Orazi, Attilio

2016-09-01

Hematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples. This study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna-Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis. Compared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna-Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis. HSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna-Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

The Effect of Traditional Chinese Formula Danchaiheji on the Differentiation of Regulatory Dendritic Cells

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Yingxi Li

2016-01-01

Full Text Available Recently, regulatory dendritic cells (DCregs, a newly described dendritic cell subset with potent immunomodulatory function, have attracted increased attention for their utility in treating immune response-related diseases, such as graft-versus-host disease, hypersensitivity, and autoimmune diseases. Danchaiheji (DCHJ is a traditional Chinese formula that has been used for many years in the clinic. However, whether DCHJ can program dendritic cells towards a regulatory phenotype and the underlying mechanism behind this process remain unknown. Herein, we investigate the effects of traditional Chinese DCHJ on DCregs differentiation and a mouse model of skin transplantation. The current study demonstrates that DCHJ can induce dendritic cells to differentiate into DCregs, which are represented by high CD11b and low CD86 and HLA-DR expression as well as the secretion of IL-10 and TGF-β. In addition, DCHJ inhibited DC migration and T cell proliferation, which correlated with increased IDO expression. Furthermore, DCHJ significantly prolonged skin graft survival time in a mouse model of skin transplantation without any liver or kidney toxicity. The traditional Chinese formula DCHJ has the potential to be a potent immunosuppressive agent with high efficiency and nontoxicity.

The Effect of Traditional Chinese Formula Danchaiheji on the Differentiation of Regulatory Dendritic Cells

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Wang, Xiaodong; Tong, Jingzhi; Li, Keqiu; Jing, Yaqing

2016-01-01

Recently, regulatory dendritic cells (DCregs), a newly described dendritic cell subset with potent immunomodulatory function, have attracted increased attention for their utility in treating immune response-related diseases, such as graft-versus-host disease, hypersensitivity, and autoimmune diseases. Danchaiheji (DCHJ) is a traditional Chinese formula that has been used for many years in the clinic. However, whether DCHJ can program dendritic cells towards a regulatory phenotype and the underlying mechanism behind this process remain unknown. Herein, we investigate the effects of traditional Chinese DCHJ on DCregs differentiation and a mouse model of skin transplantation. The current study demonstrates that DCHJ can induce dendritic cells to differentiate into DCregs, which are represented by high CD11b and low CD86 and HLA-DR expression as well as the secretion of IL-10 and TGF-β. In addition, DCHJ inhibited DC migration and T cell proliferation, which correlated with increased IDO expression. Furthermore, DCHJ significantly prolonged skin graft survival time in a mouse model of skin transplantation without any liver or kidney toxicity. The traditional Chinese formula DCHJ has the potential to be a potent immunosuppressive agent with high efficiency and nontoxicity. PMID:27525028

Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

Science.gov (United States)

Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

2008-02-01

Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

Splenic trauma: three pronged diagnosis

International Nuclear Information System (INIS)

Owens, M.L.; Brantigan, J.; Chang, F.

1975-01-01

Peritoneal lavage, splenic scan, and splenic arteriography can vastly increase the speed and accuracy of patient evaluation when splenic injury is suspected. Although certain pitfalls exist, their wider use is advocated

Regulatory dendritic cell therapy: from rodents to clinical application

OpenAIRE

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

2013-01-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant...

Induction and identification of rabbit peripheral blood derived dendritic cells

Science.gov (United States)

Zhou, Jing; Yang, FuYuan; Chen, WenLi

2012-03-01

Purpose: To study a method of the induction of dendritic cells (DCs) from rabbit peripheral blood. Methods: Peripheral blood cells were removed from rabbit, filtered through nylon mesh. Peripheral blood mononuclear cells (PBMC) were isolated from the blood cells by Ficoll-Hypaque centrifugation (density of 1.077g/cm3).To obtain DCs, PBMC were cultured in RPMI1640 medium containing 10% fetal calf serum, 50U/mL penicillin and streptomycin, referred to subsequently as complete medium, at 37°C in 5% CO2 atmosphere for 4 hours. Nonadherent cells were aspirated, adherent cells were continued incubated in complete medium, supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF, 50ng/ml),and interleukin 4 (IL-4, 50ng/ml) for 9 days. Fluorescein labeled antibodies(anti-CD14, anti-HLA-DR, anti-CD86) were used to sign cells cultured for 3,6,9 days respectively, Then flow cytometry was performed. Results: Ratio of anti-HLA-DR and anti-CD86 labeled cells increased with induction time extension, in contrast with anti-CD14. Conclusion: Dendritic cells can be effectively induced by the method of this experiment, cell maturation status increased with induction time extension.

Collagen I-induced dendritic cells activation is regulated by TNF-α ...

Indian Academy of Sciences (India)

2015-02-04

Feb 4, 2015 ... tion factor IRF4, when compared to collagen I only treated cells. Collectively, our ... and multiple scelerosis, use of TNF-α inhibitors is an important treatment ..... sclerosis complex 1 in dendritic cell activation of CD4 T cells by.

Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1

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Abediankenari Saeid

2009-10-01

Full Text Available During antigen capture and processing, mature dendritic cells (DC express large amounts of peptide-MHC complexes and accessory molecules on their surface. We investigated the role of IFN-β in induction HLA-G expression on the monocyte derived DC and cytokine profile in diabetes type 1. We accomplished secretary pattern and total cytokine production of the Th1 cytokine (IL-2, γIFN and Th2 cytokines (IL-4, IL-10 before and after mixed leukocyte reaction (MLR of 30 diabetic patients and 30 normal subjects.   In this study a significant increase of IL-10 and γIFN reduction after IFN-β Therapy in culture in presence of HLA-G bearing DC as compared to control were seen. It is seen that dendritic cell causes IL-10 production of T cell in vitro that reduce T cell activation from diabetes patients and normal subjects resulted to the production and expression of HLA-G on these cells from both groups. Using mixed leukocyte reaction, it was found that IFN-β-treated dendritic cell mediated the inhibition of autologous T cell activation via IL-10 production and level of HLA-G on dendritic cell may be correlated to disease activity in diabetes patients and it could also serve as a useful marker for disease progress and treatment.

Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice.

Science.gov (United States)

Heuss, Neal D; Pierson, Mark J; Montaniel, Kim Ramil C; McPherson, Scott W; Lehmann, Ute; Hussong, Stacy A; Ferrington, Deborah A; Low, Walter C; Gregerson, Dale S

2014-08-13

Immune system cells are known to affect loss of neurons due to injury or disease. Recruitment of immune cells following retinal/CNS injury has been shown to affect the health and survival of neurons in several models. We detected close, physical contact between dendritic cells and retinal ganglion cells following an optic nerve crush, and sought to understand the underlying mechanisms. CD11c-DTR/GFP mice producing a chimeric protein of diphtheria toxin receptor (DTR) and GFP from a transgenic CD11c promoter were used in conjunction with mice deficient in MyD88 and/or TRIF. Retinal ganglion cell injury was induced by an optic nerve crush, and the resulting interactions of the GFPhi cells and retinal ganglion cells were examined. Recruitment of GFPhi dendritic cells to the retina was significantly compromised in MyD88 and TRIF knockout mice. GFPhi dendritic cells played a significant role in clearing fluorescent-labeled retinal ganglion cells post-injury in the CD11c-DTR/GFP mice. In the TRIF and MyD88 deficient mice, the resting level of GFPhi dendritic cells was lower, and their influx was reduced following the optic nerve crush injury. The reduction in GFPhi dendritic cell numbers led to their replacement in the uptake of fluorescent-labeled debris by GFPlo microglia/macrophages. Depletion of GFPhi dendritic cells by treatment with diphtheria toxin also led to their displacement by GFPlo microglia/macrophages, which then assumed close contact with the injured neurons. The contribution of recruited cells to the injury response was substantial, and regulated by MyD88 and TRIF. However, the presence of these adaptor proteins was not required for interaction with neurons, or the phagocytosis of debris. The data suggested a two-niche model in which resident microglia were maintained at a constant level post-optic nerve crush, while the injury-stimulated recruitment of dendritic cells and macrophages led to their transient appearance in numbers equivalent to or greater

A rare case of splenic littoral cell angioma in a child

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Recep Bedir

2014-01-01

Full Text Available Littoral cell angioma (LCA is a rare, benign primary vascular neoplasm of the spleen. The tumor originates from the littoral cells lining the sinuses of the red pulp of the spleen. Preoperative distinction of this tumor from other benign or malign splenic lesions is difficult. Radiologically most cases present as multiple nodules. Definitive diagnosis can only be made histopathologically and immunohistochemically following splenectomy. This clinical situation can coexist with various malignancies and autoimmune disorders. Even though, it is mostly benign, since it has the potential to become malignant after splenectomy, long-term follow-up is required. We present an LCA case, which appeared as a solitary mass in the spleen of an 11-year-old girl with abdominal pain admitted to our hospital.

Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates corticotropin-releasing hormone expression

NARCIS (Netherlands)

Zhou, Tian; Wang, Shanshan; Ren, Haigang; Qi, Xin-Rui; Luchetti, Sabina; Kamphuis, Willem; Zhou, Jiang-Ning; Wang, Guanghui; Swaab, Dick F.

2010-01-01

The recently discovered dendritic cell nuclear protein-1 is the product of a novel candidate gene for major depression. The A allele encodes full-length dendritic cell nuclear protein-1, while the T allele encodes a premature termination of translation at codon number 117 on chromosome 5. In the

Isolation of dendritic-cell-like S100β-positive cells in rat anterior pituitary gland.

Science.gov (United States)

Horiguchi, Kotaro; Fujiwara, Ken; Yoshida, Saishu; Higuchi, Masashi; Tsukada, Takehiro; Kanno, Naoko; Yashiro, Takashi; Tateno, Kozue; Osako, Shunji; Kato, Takako; Kato, Yukio

2014-07-01

S100β-protein-positive cells in the anterior pituitary gland appear to possess multifunctional properties. Because of their pleiotropic features, S100β-positive cells are assumed to be of a heterogeneous or even a non-pituitary origin. The observation of various markers has allowed these cells to be classified into populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. The isolation and characterization of each heterogeneous population is a prerequisite for clarifying the functional character and origin of the cells. We attempt to isolate two of the subpopulations of S100β-positive cells from the anterior lobe. First, from transgenic rats that express green fluorescent protein (GFP) driven by the S100β protein promoter, we fractionate GFP-positive cells with a cell sorter and culture them so that they can interact with laminin, a component of the extracellular matrix. We observe that one morphological type of GFP-positive cells possesses extended cytoplasmic processes and shows high adhesiveness to laminin (process type), whereas the other is round in shape and exhibits low adherence to laminin (round type). We successfully isolate cells of the round type from the cultured GFP-positive cells by taking advantage of their low affinity to laminin and then measure mRNA levels of the two cell types by real-time polymerase chain reaction. The resultant data show that the process type expresses vimentin (mesenchymal cell marker) and glial fibrillary acidic protein (astrocyte marker). The round type expresses dendritic cell markers, CD11b and interleukin-6. Thus, we found a method for isolating dendritic-cell-like S100β-positive cells by means of their property of adhering to laminin.

Splenic function after angioembolization for splenic trauma in children and adults: A systematic review

NARCIS (Netherlands)

Schimmer, J. A. G.; van der Steeg, A. F. W.; Zuidema, W. P.

2016-01-01

Splenic artery embolization (SAE), proximal or distal, is becoming the standard of care for traumatic splenic injury. Theoretically the immunological function of the spleen may be preserved, but this has not yet been proven. A parameter for measuring the remaining splenic function must therefore be

Splenic function after angioembolization for splenic trauma in children and adults: A systematic review.

Science.gov (United States)

Schimmer, J A G; van der Steeg, A F W; Zuidema, W P

2016-03-01

Splenic artery embolization (SAE), proximal or distal, is becoming the standard of care for traumatic splenic injury. Theoretically the immunological function of the spleen may be preserved, but this has not yet been proven. A parameter for measuring the remaining splenic function must therefore be determined in order to decide whether or not vaccinations and/or antibiotic prophylaxis are necessary to prevent an overwhelming post-splenectomy infection (OPSI). A systematic review of the literature was performed July 2015 by searching the Embase and Medline databases. Articles were eligible if they described at least two trauma patients and the subject was splenic function. Description of procedure and/or success rate of SAE was not necessary for inclusion. Two reviewers independently assessed the eligibility and the quality of the articles and performed the data extraction. Twelve studies were included, eleven with adult patients and one focusing on children. All studies used different parameters to assess splenic function. None of them reported a OPSI after splenic embolization. Eleven studies found a preserved splenic function after SAE, in both adults and children. All but one studies on the long term effects of SAE indicate a preserved splenic function. However, there is still no single parameter or test available which can demonstrate that unequivocally. Copyright © 2015 Elsevier Ltd. All rights reserved.

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

Science.gov (United States)

Rudolph, Stephanie; Hull, Court; Regehr, Wade G

2015-11-25

Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). GoCs are excited by mossy fibers (MFs) and grcs and provide feedforward and feedback inhibition to grcs. Here we investigate two important aspects of GoC physiology: the properties of GoC dendrites and the role of calcium signaling in regulating GoC spontaneous activity. Although GoC dendrites are extensive, previous studies concluded they are devoid of voltage-gated ion channels. Hence, the current view holds that somatic voltage signals decay passively within GoC dendrites, and grc synapses onto distal dendrites are not amplified and are therefore ineffective at firing GoCs because of strong passive attenuation. Using whole-cell recording and calcium imaging in rat slices, we find that dendritic voltage-gated sodium channels allow somatic action potentials to activate voltage-gated calcium channels (VGCCs) along the entire dendritic length, with R-type and T-type VGCCs preferentially located distally. We show that R- and T-type VGCCs located in the dendrites can boost distal synaptic inputs and promote burst firing. Active dendrites are thus critical to the regulation of GoC activity, and consequently, to the processing of input to the cerebellar cortex. In contrast, we find that N-type channels are preferentially located near the soma, and control the frequency and pattern of spontaneous firing through their close association with calcium-activated potassium (KCa) channels. Thus, VGCC types are differentially distributed and serve specialized functions within GoCs. Interneurons are essential to neural processing because they modulate excitability, timing, and synaptic integration within circuits. At the input layer of the cerebellar cortex, a single type of interneuron, the Golgi cell (GoC), carries these functions. The

Overview of Nonoperative Blunt Splenic Injury Management with Associated Splenic Artery Pseudoaneurysm.

Science.gov (United States)

Morrison, Chet A; Gross, Brian W; Kauffman, Matthew; Rittenhouse, Katelyn J; Rogers, Frederick B

2017-06-01

The delayed development of splenic artery pseudoaneurysm (SAP) can complicate the nonoperative management of splenic injuries. We sought to determine the utility of repeat imaging in diagnosing SAP in patients managed nonoperatively without angioembolization. We hypothesized that a significant rate of SAPs would be found in this population on repeat imaging. Patients undergoing nonoperative splenic injury management from January 2011 to June 2015 were queried from the trauma registry. Rates of repeat imaging, angioembolization, readmission, and SAP development were analyzed. Further, subanalyses investigating the incidence of SAP in patients managed nonoperatively without angioembolization were conducted. A total of 133 patients met inclusion criteria. Repeat imaging rate was 40 per cent, angioembolization rate was 26 per cent, and readmission rate was 6 per cent. Within the study population, nine SAPs were found (8/9 in patients with splenic injury grade ≥III). Of these nine SAPs, three (33%) were identified on initial scans and embolized, whereas six (67%) were found on repeat imaging in patients not initially receiving angioembolization. Splenic injuries are typically managed nonoperatively without serious complications. Our results suggest patients with splenic injuries grade ≥III managed nonoperatively without angioembolization should have repeat imaging within 48 hours to rule out the possibility of SAP.

Generation of blood-derived dendritic cells in dogs with oral malignant melanoma.

Science.gov (United States)

Catchpole, B; Stell, A J; Dobson, J M

2002-01-01

Advances in treatment of human melanoma indicate that immunotherapy, particularly dendritic cell (DC) immunization, may prove useful. The aim of this study was to investigate whether blood-derived DCs could be generated from canine melanoma patients. Peripheral blood mononuclear cells were isolated from three such dogs and cultured with recombinant canine granulocyte-macrophage colony stimulating factor (GM-CSF), canine interleukin 4 and human Flt3-ligand for 7 days. The resulting cells demonstrated a typical dendritic morphology, and were enriched for cells expressing CD1a, CD11c and MHC II by flow cytometric analysis. Thus, canine blood-derived DCs can be generated in vitro and DC immunization should be feasible in dogs. Copyright Harcourt Publishers Ltd.

Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

Science.gov (United States)

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

The microRNA bantam regulates a developmental transition in epithelial cells that restricts sensory dendrite growth

OpenAIRE

Jiang, Nan; Soba, Peter; Parker, Edward; Kim, Charles C.; Parrish, Jay Z.

2014-01-01

As animals grow, many early born structures grow by cell expansion rather than cell addition; thus growth of distinct structures must be coordinated to maintain proportionality. This phenomenon is particularly widespread in the nervous system, with dendrite arbors of many neurons expanding in concert with their substrate to sustain connectivity and maintain receptive field coverage as animals grow. After rapidly growing to establish body wall coverage, dendrites of Drosophila class IV dendrit...

Evaluation of in vivo labelled dendritic cell migration in cancer patients.

Science.gov (United States)

Ridolfi, Ruggero; Riccobon, Angela; Galassi, Riccardo; Giorgetti, Gianluigi; Petrini, Massimiliano; Fiammenghi, Laura; Stefanelli, Monica; Ridolfi, Laura; Moretti, Andrea; Migliori, Giuseppe; Fiorentini, Giuseppe

2004-07-30

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with 99mTc-HMPAO or 111In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20-60 min after inoculation and the maximum concentration was reached after 48-72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC.

Role of Natural Killer and Dendritic Cell Crosstalk in Immunomodulation by Commensal Bacteria Probiotics

DEFF Research Database (Denmark)

Rizzello, Valeria; Bonaccorsi, Irene; Dongarra, Maria Luisa

2011-01-01

A cooperative dialogue between natural killer (NK) cells and dendritic cells (DCs) has been elucidated in the last years. They help each other to acquire their complete functions, both in the periphery and in the secondary lymphoid organs. Thus, NK cells' activation by dendritic cells allows the ......-dependent immunomodulatory effects. We particularly aim to highlight the ability of distinct species of commensal bacterial probiotics to differently affect the outcome of DC/NK cross-talk and consequently to differently influence the polarization of the adaptive immune response....

A unique cause of intestinal and splenic infarction in a sickle cell trait patient.

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Asfaw, Sofya H; Falk, Gavin A; Morris-Stiff, Gareth; Tuthill, Ralph J; Moorman, Matthew L; Samotowka, Michael A

2013-01-01

Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies.

A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

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Sofya H. Asfaw

2013-01-01

Full Text Available Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies.

CD11c-targeted Delivery of DNA to Dendritic Cells Leads to cGAS- and STING-dependent Maturation

DEFF Research Database (Denmark)

Laursen, Marlene F.; Christensen, Esben; Degn, Laura L.T.

2018-01-01

monocyte-derived dendritic cells (moDC) and human monocytic THP-1 cells to targeted and untargeted DNA. We used an anti-CD11c antibody conjugated with double-stranded DNA to analyze the maturation status of human moDCs, as well as maturation using a cGAS KO and STING KO THP-1 cell maturation model. We...... with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of dangerassociated molecular patterns...... derived from the tumor cells. Doublestranded DNA play a particularly important role in the activation of the dendritic cells, through engagement of intracellular DNAsensors, and signaling through the adaptor protein STING. In the present study, we have investigated the maturational response of human...

Dendritic cells during Epstein Barr virus infection

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Christian eMunz

2014-06-01

Full Text Available Epstein Barr virus (EBV causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This -herpesvirus infects primarily human B and epithelial cells, but has been reported to be sensed by dendritic cells (DCs during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV specific vaccine development will be discussed in this review.

Massive splenic infarction in children with sickle cell anemia and the role of splenectomy.

Science.gov (United States)

Al-Salem, Ahmed H

2013-03-01

Massive splenic infarction (MSI) is a very rare condition. Few reports of splenic infarction of various etiologies including hematological and non-hematological causes have been published. On the other hand, MSI in patients with sickle cell anemia (SCA) is extremely rare. This report describes our experience with 15 children with SCA and MSI outlining aspects of presentation, diagnosis and management. The records of all children with MSI were retrospectively reviewed for age at diagnosis, sex, clinical features, precipitating factors, investigations, management and outcome. 15 children (11 M: 4 F) with SCA were treated for MSI. Their mean age was 10.9 years (6-17 years). All presented with severe left upper quadrant abdominal pain. In nine, this was associated with nausea and vomiting. Three were febrile and all had a tender splenomegaly. Their mean hemoglobin was 8.2 g/dl (5.7-11.3 g/dl), mean WBC was 10.97 × 10(3) mm(-3) (3.6 × 10(3)-22.3 × 10(3) mm(-3)) and mean platelet count was 263.3 × 10(3) mm(-3) (40 × 10(3)-660 × 10(3) mm(-3)). In seven, there was a precipitating cause including high altitude in two, acute chest syndrome in two, septicemia in two and severe vasooclusive crisis in one. Abdominal ultrasound and CT scan confirmed the diagnosis of MSI which involved more than half of the spleen in 12 and whole spleen in 3. All were treated with IV fluids, analgesia and blood transfusion where appropriate. Eleven had splenectomy because of persistent abdominal pain, three developed splenic abscess and underwent splenectomy and one settled on conservative treatment. Histology confirmed the diagnosis of splenic infarction in 11 and infarction with abscess in the remaining 3. MSI is extremely rare in children with SCA. It can develop spontaneously or precipitated by other factors namely high altitude, acute chest syndrome and severe stress. Most reported cases of splenic infarction are small in size, focal and can be treated conservatively. MSI, on the other

Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules

DEFF Research Database (Denmark)

Bech, Rikke; Jalilian, Babak; Agger, Ralf

2016-01-01

BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part...... influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed...

B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

Directory of Open Access Journals (Sweden)

Larimore Kevin

2012-06-01

Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

Science.gov (United States)

Sonobe, Yoshifumi; Li, Hua; Jin, Shijie; Kishida, Satoshi; Kadomatsu, Kenji; Takeuchi, Hideyuki; Mizuno, Tetsuya; Suzumura, Akio

2012-03-15

Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg-mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.

Role of Dendritic Cells in Immune Dysfunction

Science.gov (United States)

Savary, Cherylyn A.

1997-01-01

Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

A phagocytotic inducer from herbal constituent, pentagalloylglucose enhances lipoplex-mediated gene transfection in dendritic cells.

Science.gov (United States)

Kato, Shinichiro; Koizumi, Keiichi; Yamada, Miyuki; Inujima, Akiko; Takeno, Nobuhiro; Nakanishi, Tsuyoshi; Sakurai, Hiroaki; Nakagawa, Shinsaku; Saiki, Ikuo

2010-01-01

Antigen-presenting cells are key vehicles for delivering antigens in tumor immunotherapy, and the most potent of them are dendritic cells (DCs). Recent studies have demonstrated the usefulness of DCs genetically modified by lipofection in tumor immune therapy, although sufficient gene transduction into DCs is quite difficult. Here, we show that Paeoniae radix, herbal medicine, and the constituent, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), have an attractive function to enhance phagocytosis in murine dendritic cell lines, DC2.4 cells. In particular, PGG in combination with lipofectin (LPF) enhanced phagocytic activity. Furthermore, PGG enhanced lipofection efficacy in DC2.4 cells, but not in colorectal carcinoma cell lines, Colon26. In other words, PGG synergistically enhanced the effect of lipofectin-dependent phagocytosis on phagocytic cells. Hence, according to our data, PGG could be an effective aid in lipofection using dendritic cells. Furthermore, these findings provide an expectation that constituents from herbal plant enhance lipofection efficacy.

Dendritic cell neurofibroma sine pseudorosettes: report of a case with a granulomatous appearance.

Science.gov (United States)

Petersson, Fredrik

2011-10-01

An unusual variant of dendritic cell neurofibroma is reported. In contrast to previous cases, the formation of pseudorosettes was lacking. The tumor was located on the anterior aspect of the thigh in a previously healthy 71-year-old woman with no evidence of neurofibromatosis. The tumor was composed of type-1 and type-2 cells, which were immunoreactive for S-100 protein and CD57. The granulomatous appearance was due to the zonal accumulation of CD34-positive dendritic cells and type-1 cells in a serpiginous fashion surrounding large areas with lesser cellularity featuring type-2 cells with scattered type-1 cells arranged in a haphazard fashion. Intralesional small neurites positive for neurofilament and perilesional perineural cells positive for epithelial membrane antigen were documented immunohistochemically.

CD1 and major histocompatibility complex II molecules follow a different course during dendritic cell maturation

NARCIS (Netherlands)

van der Wel, Nicole N.; Sugita, Masahiko; Fluitsma, Donna M.; Cao, Xaiochun; Schreibelt, Gerty; Brenner, Michael B.; Peters, Peter J.

2003-01-01

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class IT compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

International Nuclear Information System (INIS)

Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

2010-01-01

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4 + CD25 high Foxp3 + regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase.

Science.gov (United States)

Patil, Sonali; Pincas, Hanna; Seto, Jeremy; Nudelman, German; Nudelman, Irina; Sealfon, Stuart C

2010-10-07

Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks. We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to pathogen detection. This map represents a navigable

Splenic B cells and antigen-specific B cells process anti-Ig in a similar manner

International Nuclear Information System (INIS)

Myers, C.D.; Vitetta, E.S.

1989-01-01

B lymphocytes can process and present antigen to T cells. However, the fate of native antigen after its binding to specific B cells, i.e., the intracellular events involved in the processing and recycling of the antigenic fragments to the cell surface for antigen presentation, are not well understood. In the present study, we demonstrate that murine B cells degrade anti-Ig molecules bound to their surface and release acid soluble fragments into the supernatant. We also demonstrate that the kinetics of this process are identical for anti-mu, anti-delta, and anti-light chain antibodies, indicating that both surface IgM and surface IgD are equally effective in binding antigen and directing its processing. We also describe the effects of azide, chloroquine, and irradiation on this process. To extend these studies to the processing of specifically bound antigen, we demonstrate that highly purified trinitrophenyl antigen-binding cells degrade anti-Ig molecules with the same kinetics as unpurified splenic B cells. Thus, this purified population provides a suitable model system for the analysis of antigen degradation by antigen-specific cells

Thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism.

Science.gov (United States)

Duan, Ya-Qi; Liang, Ping

2013-05-01

Many studies have been conducted on splenic thermal ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In this article, we review the evolution and current status of radiofrequency and microwave ablation in the treatment of spleen diseases. All publications from 1990 to 2011 on radiofrequency and microwave ablation for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism were retrieved by searching PubMed. Thermal ablation in the spleen for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism can preserve part of the spleen and maintain splenic immunologic function. Thermal ablation for assisting hemostasis in partial splenectomy minimizes blood loss during operation. Thermal ablation for spleen trauma reduces the number of splenectomy and the amount of blood transfusion. Thermal ablation for splenic metastasis is minimally invasive and can be done under the guidance of an ultrasound, which helps shorten the recovery time. Thermal ablation for hypersplenism increases platelet (PLT) and white blood cell (WBC) counts and improves liver function. It also helps to maintain splenic immunologic function and even improves splenic immunologic function in the short-term. In conclusion, thermal ablative approaches are promising for partial splenectomy hemostasis, spleen trauma, splenic metastasis and hypersplenism. In order to improve therapeutic effects, directions for future studies may include standardized therapeutic indications, prolonged observation periods and enlarged sample sizes.

Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients

DEFF Research Database (Denmark)

Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan

2008-01-01

The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1...... polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC......-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza...

Dendritic cells and skin sensitization: Biological roles and uses in hazard identification

International Nuclear Information System (INIS)

Ryan, Cindy A.; Kimber, Ian; Basketter, David A.; Pallardy, Marc; Gildea, Lucy A.; Gerberick, G. Frank

2007-01-01

Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development of cellular assays (using DC and DC-like cells) for skin sensitization hazard identification. These alternative approaches to the identification and characterization of skin sensitizing chemicals were the focus of a Workshop entitled 'Dendritic Cells and Skin Sensitization: Biological Roles and Uses in Hazard Identification' that was given at the annual Society of Toxicology meeting held March 6-9, 2006 in San Diego, California. This paper reports information that was presented during the Workshop

Targeting dendritic cells in vivo for cancer therapy

Directory of Open Access Journals (Sweden)

Irina eCaminschi

2012-02-01

Full Text Available Monoclonal antibodies that recognise cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC for induction of immune responses. The encouraging anti-tumour immunity elicited using this immunisation strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialisation of DC-subsets, the immunological outcomes of targeting different DC-subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumour immunity. Finally, we review preclinical experiments and the progress towards targeting human DC in vivo.

Dendritic cell populations in patients with self-reported food hypersensitivity

Directory of Open Access Journals (Sweden)

Lied GA

2011-05-01

Full Text Available Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

Science.gov (United States)

Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

2011-01-01

Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

Higher incidence of major complications after splenic embolization for blunt splenic injuries in elderly patients.

Science.gov (United States)

Wu, Shih-Chi; Fu, Chih-Yuan; Chen, Ray-Jade; Chen, Yung-Fang; Wang, Yu-Chun; Chung, Ping-Kuei; Yu, Shu-Fen; Tung, Cheng-Cheng; Lee, Kun-Hua

2011-02-01

Nonoperative management (NOM) of blunt splenic injuries has been widely accepted, and the application of splenic artery embolization (SAE) has become an effective adjunct to NOM. However, complications do occur after SAE. In this study, we assess the factors leading to the major complications associated with SAE. Focusing on the major complications after SAE, we retrospectively studied patients who received SAE and were admitted to 2 major referral trauma centers under the same established algorithm for management of blunt splenic injuries. The demographics, angiographic findings, and factors for major complications after SAE were examined. Major complications were considered to be direct adverse effects arising from SAE that were potentially fatal or were capable of causing disability. There were a total of 261 patients with blunt splenic injuries in this study. Of the 261 patients, 53 underwent SAE, 11 (21%) of whom were noted to have 12 major complications: 8 cases of postprocedural bleeding, 2 cases of total infarction, 1 case of splenic abscess, and 1 case of splenic atrophy. Patients older than 65 years were more susceptible to major complications after SAE. Splenic artery embolization is considered an effective adjunct to NOM in patients with blunt splenic injuries. However, risks of major complications do exist, and being elderly is, in part, associated with a higher major complication incidence. Copyright © 2011 Elsevier Inc. All rights reserved.

Splenic abscess: a rare presentation

Directory of Open Access Journals (Sweden)

Mohit Bhatia

2015-01-01

Full Text Available Splenic abscess is a rare clinical entity with an incidence of 0.2-0.7% in autopsy-based studies. When untreated, splenic abscess is associated with nearly 100% mortality; in treated patients, the mortality rate is 16.6% during the first 90 days. It mostly occurs in patients with neoplasia, immunodeficiency, trauma, diabetes or splenic infarct. The incidence of splenic abscess is thought to be growing because of the increase in the number of immunocompromised patients who are particularly at risk for this disease and also because of the widespread use of diagnostic modalities. However, the optimal treatment for this remains unclear. We present a case of a 42-year-old man diagnosed with multiloculated splenic abscess and was subjected to splenectomy.

Differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses to single epicutaneous immunization.

Science.gov (United States)

Lee, Chih-Hung; Chen, Jau-Shiuh; Chiu, Hsien-Ching; Hong, Chien-Hui; Liu, Ching-Yi; Ta, Yng-Cun; Wang, Li-Fang

2016-12-01

Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice. We characterized dermal dendritic cells by flow cytometric analysis. We measured the induced Th1/Th2 responses by measuring the IFN-γ/IL-13 contents of supernatants of antigen reactivation cultures of lymph node cells. We demonstrate that more dermal dendritic cells with higher activation status migrate into draining lymph nodes of B6 mice compared to BALB/c mice. Dermal dendritic cells of B6 mice have a greater ability to capture protein antigen than those of BALB/c mice. Moreover, increasing the activation status or amount of captured antigen in dermal dendritic cells induced a Th1 response in BALB/c mice. Further, differential activation behavior, but not antigen-capturing ability of dermal dendritic cells between BALB/c and B6 mice is dendritic cell-intrinsic. These results show that the differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses following single epicutaneous immunization. Furthermore, our findings highlight the potential differences between human atopics and non-atopics and provide useful information for the prediction and prevention of atopic diseases. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

National Research Council Canada - National Science Library

Mule, James

1998-01-01

The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene-modified fibroblasts with breast tumor-pulsed dendritic cells (DC...

Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

National Research Council Canada - National Science Library

Mule, James

1997-01-01

The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene modified fibroblasts with breast tumor pulsed dendritic cells (DC...

Macrophage-mediated gliadin degradation and concomitant IL-27 production drive IL-10- and IFN-γ-secreting Tr1-like-cell differentiation in a murine model for gluten tolerance.

Science.gov (United States)

van Leeuwen, M A; Costes, L M M; van Berkel, L A; Simons-Oosterhuis, Y; du Pré, M F; Kozijn, A E; Raatgeep, H C; Lindenbergh-Kortleve, D J; van Rooijen, N; Koning, F; Samsom, J N

2017-05-01

Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process. In vivo depletion of macrophages caused reduced differentiation of splenic IFN-γ- and IL-10-producing Tr1-like cells after CT-TG2-gliadin but not gliadin peptide feed. Splenic macrophages, rather than dendritic cells, constitutively expressed increased mRNA levels of the endopeptidase Cathepsin D; macrophage depletion significantly reduced splenic Cathepsin D expression in vivo and Cathepsin D efficiently degraded recombinant γ-gliadin in vitro. In response to CT-TG2-gliadin uptake, macrophages enhanced the expression of Il27p28, a cytokine that favored differentiation of gliadin-specific Tr1-like cells in vitro, and was previously reported to increase Cathepsin D activity. Conversely, IL-27 neutralization in vivo inhibited splenic IFN-γ- and IL-10-secreting Tr1-like-cell differentiation after CT-TG2-gliadin feed. Our data infer that endopeptidase mediated gliadin degradation by macrophages and concomitant IL-27 production drive differentiation of splenic gliadin-specific Tr1-like cells.

Blastic Plasmacytoid Dendritic Cell Leukemia in a Black Malian

African Journals Online (AJOL)

2017-06-28

Jun 28, 2017 ... BPDCN in Mali. KEYWORDS: Acute Leukemia, black african, dendritic cell, Mali ... myeloid neoplasm by the 2008 world health organization classification of .... There are many standardized treatment regimens, and many protocols with ... leukemia chemotherapy regimen[7,11] or chronic leukemia treatment ...

Evaluation of in vivo labelled dendritic cell migration in cancer patients

Directory of Open Access Journals (Sweden)

Ridolfi Laura

2004-07-01

Full Text Available Abstract Background Dendritic Cell (DC vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC with that of immature Dendritic Cells (iDC and also assessed intradermal versus subcutaneous administration. Methods DC were labelled with 99mTc-HMPAO or 111In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma. Results It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20–60 min after inoculation and the maximum concentration was reached after 48–72 h. Conclusions These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC.

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

DEFF Research Database (Denmark)

Sørensen, C.M.; Holmskov, U.; Aalbæk, B.

2005-01-01

, the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of p...... and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.......Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic...

Effects of Aedes aegypti salivary components on dendritic cell and lymphocyte biology

Czech Academy of Sciences Publication Activity Database

Bizzarro, B.; Barros, M.S.; Maciel, C.; Gueroni, D.I.; Lino, C.N.; Campopiano, J.; Kotsyfakis, Michalis; Amarante-Mendes, G.P.; Calvo, E.; Capurro, M.L.; Sa-Nunes, A.

2013-01-01

Roč. 6, NOV 2013 (2013), s. 329 ISSN 1756-3305 Institutional support: RVO:60077344 Keywords : dendritic cells * T-cells * Aedes aegypti * saliva * apoptosis Subject RIV: EC - Immunology Impact factor: 3.251, year: 2013

[Splenic infarction].

Science.gov (United States)

Cuquerella, J; Ferrer, L; Rivera, P; Tuset, J A; Medina, E; Pamós, S; Ariete, V; Tomé, A; García, V

1996-06-01

A 53-year-old male suffered splenic infarction etiologically related to atrial fibrillation and non-obstructive hypertrophic cardiomyopathy. The main clinical manifestations were a one-month history of epigastric and left upper quadrant pain, with tenderness to palpation in the later zone. Laboratory tests revealed a slight leucocytosis (14.700) with left shift and a marked increase in LDH concentration (945 IU). Abdominal CAT and arteriography established the diagnosis, Echography proved normal. Patient evolution was satisfactory with conservative medical treatment. We conclude that splenic infarction should be considered in all cases of acute or chronic pain in the left hypochondrium. The diagnosis is established by CAT, arteriography and hepatosplenic gammagraphy. Medical management is initially advocated, surgery being reserved for those cases involving complications or in which diagnosis is not clear. Emphasis is placed on the main etiological, clinical, diagnostic and management characteristics of splenic infarction.

Resistivity and thickness effects in dendritic web silicon solar cells

Science.gov (United States)

Meier, D. L.; Hwang, J. M.; Greggi, J.; Campbell, R. B.

1987-01-01

The decrease of minority carrier lifetime as resistivity decreases in dendritic-web silicon solar cells is addressed. This variation is shown to be consistent with the presence of defect levels in the bandgap which arise from extended defects in the web material. The extended defects are oxide precipitates (SiOx) and the dislocation cores they decorate. Sensitivity to this background distribution of defect levels increases with doping because the Fermi level moves closer to the majority carrier band edge. For high-resistivity dendritic-web silicon, which has a low concentration of these extended defects, cell efficiencies as high as 16.6 percent (4 sq cm, 40 ohm-cm boron-doped base, AM1.5 global, 100 mW/sq cm, 25 C JPL LAPSS1 measurement) and a corresponding electron lifetime of 38 microsec have been obtained. Thickness effects occur in bifacial cell designs and in designs which use light trapping. In some cases, the dislocation/precipitate defect can be passivated through the full thickness of web cells by hydrogen ion implantation.

Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways

International Nuclear Information System (INIS)

Laxmanan, Sreenivas; Robertson, Stuart W.; Wang Enfeng; Lau, Julie S.; Briscoe, David M.; Mukhopadhyay, Debabrata

2005-01-01

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that plays an important role in tumor growth and progression. Recent evidence suggests an alternate, albeit indirect, role of VEGF on host immune response to tumors. VEGF appears to diminish host immunity by altering the function of major antigen-presenting cells such as dendritic cells (DCs) [D.I. Gabrilovich, T. Ishida, S. Nadaf, J.E. Ohm, D.P. Carbone, Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function, Clin. Cancer Res. 5 (1999) 2963-2970, D. Gabrilovich, T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, D.P. Carbone, Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo, Blood 92 (1998) 4150-4166, T. Oyama, S. Ran, T. Ishida, S. Nadaf, L. Kerr, D.P. Carbone, D.I. Gabrilovich, Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells, J. Immunol. 160 (1998) 1224-1232.]. DCs are prime initiators of host immunity as they are known to activate both primary as well as secondary immune responses [J. Banchereau, F. Briere, C. Caux, J. Davoust, S. Lebecque, Y.J. Liu, B. Pulendran, K. Palucka, Immunobiology of dendritic cells, Ann. Rev. Immunol. 18 (2000) 767-811.]. However, the exact nature of how VEGF suppresses DC function is not fully clear. In this report, we show that DCs cultured in the presence of VEGF are less potent in stimulating antigen-specific T-cells. Furthermore, by using DCs derived from Id1 -/- mice that are defective in Flt-1 signaling, we demonstrated that the inhibitory function of VEGF on DC function is most likely mediated by Flt-1. Thus, the role of VEGF in downregulating host immunity may highlight a unique role of VEGF in the pathogenesis of cancer

Circulating dendritic cells in pediatric patients with nephrotic syndrome

African Journals Online (AJOL)

Background: Dendritic cells (DCs) represent one of the most extensively studied topics in immunology, because of their central role in the induction and regulation of adaptive immunity, and because of their therapeutic potential for manipulating immune responses. Objectives: To evaluate circulating DC levels in pediatric ...

Embolization Therapy for Traumatic Splenic Lacerations

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Niloy; Matsumoto, Alan H., E-mail: ahm4d@virginia.edu; Arslan, Bulent; Turba, Ulku C.; Sabri, Saher; Angle, John F. [University of Virginia Health System, Division of Vascular and Interventional Radiology, Department of Radiology (United States)

2012-08-15

Purpose: This study was designed to evaluate the clinical success, complications, and transfusion requirements based on the location of and agents used for splenic artery embolization in patients with splenic trauma. Methods: A retrospective study was performed of patients with splenic trauma who underwent angiography and embolization from September 2000 to January 2010 at a level I trauma center. Electronic medical records were reviewed for demographics, imaging data, technical aspects of the procedure, and clinical outcomes. Results: Fifty patients were identified (34 men and 16 women), with an average age of 48 (range, 16-80) years. Extravasation was seen on initial angiography in 27 (54%) and was absent in 23 (46%). All 27 patients with extravasation were embolized, and 18 of 23 (78.2%) without extravasation were embolized empirically. Primary clinical success was similar (>75%) across all embolization locations, embolic agents, and grades of laceration treated. Of 45 patients treated, 9 patients (20%) were embolized in the main splenic artery, 34 (75.6%) in the splenic hilum, and 2 (4.4%) were embolized in both locations. Partial splenic infarctions developed in 47.3% treated in the splenic hilum compared with 12.5% treated in the main splenic artery. There were four (8.9%) mortalities: two occurred in patients with multiple critical injuries and two from nonbleeding etiologies. Conclusions: Embolization of traumatic splenic artery injuries is safe and effective, regardless of the location of treatment. Embolization in splenic hilar branches may have a higher incidence of infarction. The grade of laceration and agents used for embolotherapy did not impact the outcomes.

Embolization Therapy for Traumatic Splenic Lacerations

International Nuclear Information System (INIS)

Dasgupta, Niloy; Matsumoto, Alan H.; Arslan, Bulent; Turba, Ulku C.; Sabri, Saher; Angle, John F.

2012-01-01

Purpose: This study was designed to evaluate the clinical success, complications, and transfusion requirements based on the location of and agents used for splenic artery embolization in patients with splenic trauma. Methods: A retrospective study was performed of patients with splenic trauma who underwent angiography and embolization from September 2000 to January 2010 at a level I trauma center. Electronic medical records were reviewed for demographics, imaging data, technical aspects of the procedure, and clinical outcomes. Results: Fifty patients were identified (34 men and 16 women), with an average age of 48 (range, 16–80) years. Extravasation was seen on initial angiography in 27 (54%) and was absent in 23 (46%). All 27 patients with extravasation were embolized, and 18 of 23 (78.2%) without extravasation were embolized empirically. Primary clinical success was similar (>75%) across all embolization locations, embolic agents, and grades of laceration treated. Of 45 patients treated, 9 patients (20%) were embolized in the main splenic artery, 34 (75.6%) in the splenic hilum, and 2 (4.4%) were embolized in both locations. Partial splenic infarctions developed in 47.3% treated in the splenic hilum compared with 12.5% treated in the main splenic artery. There were four (8.9%) mortalities: two occurred in patients with multiple critical injuries and two from nonbleeding etiologies. Conclusions: Embolization of traumatic splenic artery injuries is safe and effective, regardless of the location of treatment. Embolization in splenic hilar branches may have a higher incidence of infarction. The grade of laceration and agents used for embolotherapy did not impact the outcomes.

Dendritic Cell-Based Immunotherapy of Breast Cancer: Modulation by CpG

National Research Council Canada - National Science Library

Baar, Joseph

2004-01-01

... in the United States in 2004. Thus, patients with MBC who fail conventional therapies are candidates for clinical trials using novel therapeutic approaches, including immunotherapy. Dendritic cells (DC...

Intestinal dendritic cells in the regulation of mucosal immunity

DEFF Research Database (Denmark)

Bekiaris, Vasileios; Persson, Emma K.; Agace, William Winston

2014-01-01

immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive....... The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality...

Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells

International Nuclear Information System (INIS)

Schwarz, Sebastian; Fernandes, Fabiana; Sanroman, Laura; Hodenius, Michael; Lang, Claus; Himmelreich, Uwe; Schmitz-Rode, Thomas; Schueler, Dirk; Hoehn, Mathias

2009-01-01

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3 + stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

Directory of Open Access Journals (Sweden)

Sperling Rhoda

2011-08-01

Full Text Available Abstract Background During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response. Methods We compare culture-generated monocyte derived DCs (MDDCs with directly isolated myeloid dendritic cells (mDCs and plasmacytoid dendritic cells (pDCs and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy. Results We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients. Conclusions Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

Gliadin fragments promote migration of dendritic cells

Czech Academy of Sciences Publication Activity Database

Chládková, Barbara; Kamanová, Jana; Palová-Jelínková, Lenka; Cinová, Jana; Šebo, Peter; Tučková, Ludmila

2011-01-01

Roč. 15, č. 4 (2011), 938-948 ISSN 1582-1838 R&D Projects: GA ČR GA310/07/0414; GA ČR GD310/08/H077; GA ČR GA310/08/0447; GA AV ČR IAA500200801; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : celiac disease * gliadin * dendritic cell Subject RIV: EC - Immunology Impact factor: 4.125, year: 2011

Campylobacter jejuni, an uncommon cause of splenic abscess diagnosed by 16S rRNA gene sequencing

Directory of Open Access Journals (Sweden)

Piseth Seng

2014-12-01

Full Text Available Splenic abscess is a rare disease that primarily occurs in patients with splenic trauma, endocarditis, sickle cell anemia, or other diseases that compromise the immune system. This report describes a culture-negative splenic abscess in an immunocompetent patient caused by Campylobacter jejuni, as determined by 16S rRNA gene sequencing.

DMPD: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18641647 Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune dise... (.csml) Show Plasmacytoid dendritic cells: sensing nucleic acids in viral infection andautoimmune diseases....iral infection andautoimmune diseases. Authors Gilliet M, Cao W, Liu YJ. Publication Nat Rev Immunol. 2008 A

Clinical study on embolization syndromes after splenic arterial embolization

International Nuclear Information System (INIS)

Liu Minhua; Zhou Rumin

2004-01-01

Objective: To analyze the reaction of splenic arterial embolization (embolization syndromes) using 3 different materials together with the therapeutic methods. Methods: Thirty nine patients of cirrhosis with hypersplenism and hypersplenotrophy, 11 of them were treated with steel coils, 15 with gelfoam, 13 with the PVA. The embolized area was approximately 60% of the whole splenic area. Results: Thirty nine cases obtained the curative effect. The blood white cell and platelet counts were normal or close to normal. The rates of splenic pain in steel coils group, gelfoam group and PVA group were 81.8%, 100% and 100% respectively. The duration of serious pain were 2-5 d, 1-7 d and 1-7 d in coil group, gelfoam group and PVA group respectively. 33 patients had moderate fever around 38.5 degree C and 8 patients had eructation after embolization. The symptoms disappeared after using antibiotics, dexamethasone and analgesic. Conclusions: The algetic grade of splenic arterial embolization was inverse proportional with the size of embolus. The correct management could effectively control the symptoms of postembolization of the spleen

Splenic contraction in patients with various disorders

Energy Technology Data Exchange (ETDEWEB)

Iio, Atsushi; Murase, Kenya; Ito, Hisao; Watanabe, Yuji; Kawamura, Masashi; Hamamoto, Ken

1986-03-01

To investigate the pathophysiology of human spleen, splenic contraction following subcutaneous injection of epinephrine was measured in 45 patients with various disorders using single photon emission computed tomography (SPECT). The splenic contraction rates and percent decreases in splenic counts (ejection rates) in 5 controls were 34.5 +- 10.0 percent (mean +- SD) and 16.4 +- 6.9 percent respectively. With regard to non-Hodgkin lymphoma, the splenic contraction and ejection rates in 8 patients with no splenic involvement diagnosed by CT and/or /sup 67/Ga scintigraphy were 27.3 +- 7.0 percent and 9.4 +- 7.0 percent respectively, while these values in 6 patients with splenic involvement diagnosed by presence of splenomegaly, CT and/or /sup 67/Ga scintigraphy were 12.8 +- 5.8 percent and 2.5 +- 1.6 percent respectively. Both the values in the patients with splenic involvement were low (p < 0.01, p < 0.1) compared with those in the patients without splenic involvement. The splenic contraction and ejection rates in 7 patients with splenomegaly due to portal hypertension were averaged 33.5 +- 6.7 percent and 13.8 +- 4.5 percent respectively. These values were comparable to those in controls. All 3 patients with leukemia and splenomegaly showed exceedingly low values of the splenic contraction and ejection rates. The values were also remarkably low in a patient with splenic metastasis of unknown origin.

Signaling network of dendritic cells in response to pathogens: a community-input supported knowledgebase

Directory of Open Access Journals (Sweden)

Nudelman Irina

2010-10-01

Full Text Available Abstract Background Dendritic cells are antigen-presenting cells that play an essential role in linking the innate and adaptive immune systems. Much research has focused on the signaling pathways triggered upon infection of dendritic cells by various pathogens. The high level of activity in the field makes it desirable to have a pathway-based resource to access the information in the literature. Current pathway diagrams lack either comprehensiveness, or an open-access editorial interface. Hence, there is a need for a dependable, expertly curated knowledgebase that integrates this information into a map of signaling networks. Description We have built a detailed diagram of the dendritic cell signaling network, with the goal of providing researchers with a valuable resource and a facile method for community input. Network construction has relied on comprehensive review of the literature and regular updates. The diagram includes detailed depictions of pathways activated downstream of different pathogen recognition receptors such as Toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors and nucleotide-binding oligomerization domain-like receptors. Initially assembled using CellDesigner software, it provides an annotated graphical representation of interactions stored in Systems Biology Mark-up Language. The network, which comprises 249 nodes and 213 edges, has been web-published through the Biological Pathway Publisher software suite. Nodes are annotated with PubMed references and gene-related information, and linked to a public wiki, providing a discussion forum for updates and corrections. To gain more insight into regulatory patterns of dendritic cell signaling, we analyzed the network using graph-theory methods: bifan, feedforward and multi-input convergence motifs were enriched. This emphasis on activating control mechanisms is consonant with a network that subserves persistent and coordinated responses to

Studies on the control mechanism and the degenerative immune function of dendritic cells using radiation

International Nuclear Information System (INIS)

Yee, Sung Tae; Kim, Jong Jin; Choi, Ji Na; Park, Jung Eun; Jeong, Young Ran

2010-05-01

Dendritic cells are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and costimulatory molecule expression of spleen or bone marrow-derived CD11c + DCs of C57BL/6 mice. In the first year, we compared various function of dendritic cells isolated from young and gamma-irradiated 57BL/6 mice(5 weeks after γ-radiation) for the development of aging models using radiation. In the second year, we also compared the function of spleen- and bone marrow-derived dendritic cells of young(2-3 months) and old(23-24 months) 57BL/6 mice. And we studied the differences of spleen- and bone marrow-derived dendritic cells of young and gamma-irradiated 57BL/6 mice(2, 4, 6 months after γ-radiation) for the development of aging models in third year. And we obtained various differences between spleen- and bone marrow-derived dendritic cells of normal and old(23-24 months) or γ-irradiated 57BL/6 mice. It is possible to use our results as age-associated model for modulation of the declined immunity and hematopoiesis for treatment of cancer, adult diseases and stress in aging. Such studies on the mechanism of aging model would further lead to new avenues for the development of functional foods which effect such as pathogenesis, inflammatory and autoimmune disorders. It will contributed to activation of related industry conforming quality and diversity of radiation industry. The techniques developed in our research may provide novel therapeutic modalities for age-associated immune dysfunctions

Image guided percutaneous splenic interventions

International Nuclear Information System (INIS)

Kang, Mandeep; Kalra, Naveen; Gulati, Madhu; Lal, Anupam; Kochhar, Rohit; Rajwanshi, Arvind

2007-01-01

Aim: The objective of this study is to evaluate the efficacy and safety of image-guided percutaneous splenic interventions as diagnostic or therapeutic procedures. Materials and methods: We performed a retrospective review of our interventional records from July 2001 to June 2006. Ninety-five image-guided percutaneous splenic interventions were performed after informed consent in 89 patients: 64 men and 25 women who ranged in age from 5 months to 71 years (mean, 38.4 years) under ultrasound (n = 93) or CT (n = 2) guidance. The procedures performed were fine needle aspiration biopsy of focal splenic lesions (n = 78) and aspiration (n = 10) or percutaneous catheter drainage of a splenic abscess (n = 7). Results: Splenic fine needle aspiration biopsy was successful in 62 (83.78%) of 74 patients with benign lesions diagnosed in 43 (58.1%) and malignancy in 19 (25.67%) patients. The most common pathologies included tuberculosis (26 patients, 35.13%) and lymphoma (14 patients, 18.91%). Therapeutic aspiration or pigtail catheter drainage was successful in all (100%) patients. There were no major complications. Conclusions: Image-guided splenic fine needle aspiration biopsy is a safe and accurate technique that can provide a definitive diagnosis in most patients with focal lesions in the spleen. This study also suggests that image-guided percutaneous aspiration or catheter drainage of splenic abscesses is a safe and effective alternative to surgery

IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

DEFF Research Database (Denmark)

Luda, Katarzyna M.; Joeris, Thorsten; Persson, Emma K.

2016-01-01

The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence...... dependent DCs in the maintenance of intestinal T cell homeostasis....

Follicular dendritic cell-specific prion protein (PrP expression alone is sufficient to sustain prion infection in the spleen.

Directory of Open Access Journals (Sweden)

Laura McCulloch

2011-12-01

Full Text Available Prion diseases are characterised by the accumulation of PrP(Sc, an abnormally folded isoform of the cellular prion protein (PrP(C, in affected tissues. Following peripheral exposure high levels of prion-specific PrP(Sc accumulate first upon follicular dendritic cells (FDC in lymphoid tissues before spreading to the CNS. Expression of PrP(C is mandatory for cells to sustain prion infection and FDC appear to express high levels. However, whether FDC actively replicate prions or simply acquire them from other infected cells is uncertain. In the attempts to-date to establish the role of FDC in prion pathogenesis it was not possible to dissociate the Prnp expression of FDC from that of the nervous system and all other non-haematopoietic lineages. This is important as FDC may simply acquire prions after synthesis by other infected cells. To establish the role of FDC in prion pathogenesis transgenic mice were created in which PrP(C expression was specifically "switched on" or "off" only on FDC. We show that PrP(C-expression only on FDC is sufficient to sustain prion replication in the spleen. Furthermore, prion replication is blocked in the spleen when PrP(C-expression is specifically ablated only on FDC. These data definitively demonstrate that FDC are the essential sites of prion replication in lymphoid tissues. The demonstration that Prnp-ablation only on FDC blocked splenic prion accumulation without apparent consequences for FDC status represents a novel opportunity to prevent neuroinvasion by modulation of PrP(C expression on FDC.

The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

Science.gov (United States)

Rumfelt, L L; McKinney, E C; Taylor, E; Flajnik, M F

2002-08-01

Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

DEFF Research Database (Denmark)

Sichien, Dorine; Scott, Charlotte L; Martens, Liesbet

2016-01-01

Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the ide...

Transcriptional Changes during Naturally Acquired Zika Virus Infection Render Dendritic Cells Highly Conducive to Viral Replication.

Science.gov (United States)

Sun, Xiaoming; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Einkauf, Kevin; Tse, Samantha; Ard, Kevin; Ciaranello, Andrea; Yawetz, Sigal; Sax, Paul; Rosenberg, Eric S; Lichterfeld, Mathias; Yu, Xu G

2017-12-19

Although dendritic cells are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with the Zika virus (ZIKV). Using highly purified myeloid dendritic cells isolated from individuals with naturally acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to healthy donors. Interestingly, we noted a remarkable downregulation of antiviral interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV; SOCS3, a negative regulator of ISG expression; and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection. Published by Elsevier Inc.

Ebola virus infection induces irregular dendritic cell gene expression.

Science.gov (United States)

Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

2015-02-01

Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48 h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors.

[Sub capsular splenic hematoma in a sickle cell trait carrier. Case report].

Science.gov (United States)

Ugalde, Diego; Conte, Guillermo; Ugalde, Héctor; Figueroa, Gastón; Cuneo, Marianela; Muñoz, Macarena; Mayor, Javiera

2011-09-01

Drepanocytic anemia is an uncommon hereditary disease in Chile. The heterozygous state of drepanocytic anemia or "sickle trait" has a frequency of 8% among Afro-Americans. A small number of patients carrying hemoglobin S are homozygous, with clinical manifestations of hemolytic anemia and thrombotic disease. Sickle trait is usually asymptomatic. We report a 59-year-old male who presented an acute abdominal pain and dyspnea while staying at high altitude. Six days later, an angio CAT scan showed the presence of a subcapsular splenic hematoma that was managed conservatively. Sickle cell induction with sodium metabisulphite was positive. Hemoglobin electrophoresis confirmed the sickle trait.

Splenic epithelial cyst

International Nuclear Information System (INIS)

Yousuf, M.; Jalali, U.

2011-01-01

Cysts of spleen are rare entities. Congenital splenic cysts are even more uncommon comprising of only 10% of benign non-parasitic cysts. We report a case of 22 years old female who presented with history of 2 years abdominal pain and gradual distension. Ultrasound and computed tomography (CT) both were suggestive of splenic cyst. Laboratory tests show thrombocytopenia with platelets count of 97000 per cubic millimeter and anemia with hemoglobin 8.7 gram per deciliter. Serological tests were negative for parasitic infection. Splenectomy was done and the weight of the spleen was found to be 1.5 kilogram. Histopathological findings are consistent with splenic epithelial cyst. The aetiology, diagnostic modalities and treatment options are discussed in the case report. (author)

Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.

NARCIS (Netherlands)

Hegmans, J.P.; Veltman, J.D.; Lambers, M.E.; Vries, I.J.M. de; Figdor, C.G.; Hendriks, R.W.; Hoogsteden, H.C.; Lambrecht, B.N.; Aerts, J.G.

2010-01-01

RATIONALE: We previously demonstrated that dendritic cell-based immunotherapy induced protective antitumor immunity with a prolonged survival rate in mice. However, the clinical relevance is still in question. To examine this, we designed a clinical trial using chemotherapy followed by

Aggressive natural killer-cell leukemia with jaundice and spontaneous splenic rupture: a case report and review of the literature.

Science.gov (United States)

Gao, Li-min; Liu, Wei-ping; Yang, Qun-pei; Li, Hui-fang; Chen, Jun-jie; Tang, Yuan; Zou, Yan; Liao, Dian-Ying; Liu, Yan-mei; Zhao, Sha

2013-03-11

Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare aggressive form of NK-cell neoplasm. We report an uncommon case of 36-year-old male who showed jaundice and spontaneous splenic rupture. The diagnosis was established by the biopsy of liver and spleen. The monomorphous medium-size neoplastic cells infiltrated into portal areas and sinus of liver as well as the cords and sinus of the spleen. Necrosis, mitotic figures and significant apoptosis could be seen easily. These neoplastic cells demonstrated a typical immunophenotype of CD3ε+, CD56+, CD16+, Granzyme B+, TIA-1+. T-cell receptor γ (TCR-γ) gene rearrangement analysis showed germline configuration and the result of in situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was positive. The patient has undergone an aggressive clinical course and died of multi-organ function failure 14 days later after admission. To the best of our knowledge, this is the first case of ANKL with spontaneous splenic rupture, and we should pay more attention to recognize it. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2048154883890867.

Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

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C.M.F. Lima

2010-10-01

Full Text Available A better understanding of dendritic cell (DC involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC and myeloid DC (mDC. β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6 production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

Bone marrow dendritic cell-based anticancer vaccines

Czech Academy of Sciences Publication Activity Database

Indrová, Marie; Mendoza, Luis; Reiniš, Milan; Vonka, V.; Šmahel, M.; Němečková, Š.; Jandlová, Táňa; Bubeník, Jan

2001-01-01

Roč. 495, - (2001), s. 355-358 ISSN 0065-2598 R&D Projects: GA MZd NC5526; GA ČR GA312/98/0826; GA ČR GA312/99/0542; GA ČR GA301/00/0114; GA ČR GA301/01/0985; GA AV ČR IAA7052002 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV16 * dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.513, year: 2000

Murid herpesvirus-4 exploits dendritic cells to infect B cells.

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Miguel Gaspar

2011-11-01

Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

SPLENIC INFARCTION: an intriguing and important cause of pain abdomen in high altitude

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P. K. Hota

2015-01-01

Full Text Available Background: Patients with Sickle cell trait (SCT are usually asymptomatic. They are usually unaware of their condition unless they have a family history. There are specific situations, where these people suffer from the effects of sickle cell trait. Splenic syndrome at high altitude is one of the specific problems. It is usually seen after a patient with SCT has been inducted to high altitude like in case of mountaineers and military personnel deployed in high altitude warfare. Pain abdomen due to splenic infarction in individuals with SCT is one of the manifestations. These patients, if diagnosed in time, they can be spared from unnecessary surgical interventions. We present herewith our experience of splenic infarction due to SCT in high altitude and their management.

Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

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Andoh Y

2013-01-01

Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

Studies on mRNA electroporation of immature and mature dendritic cells

DEFF Research Database (Denmark)

Met, Ozcan; Eriksen, Jens; Svane, Inge Marie

2008-01-01

Previous studies have shown that mRNA-electroporated dendritic cells (DCs) are able to process and present tumor-associated antigens, leading to the activation of tumor-specific T cells in vitro and in vivo. However, the optimal maturation state of antigen loading and half-life of the mRNA-transl...

Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression.

Science.gov (United States)

Han, Yanmei; Liu, Qiuyan; Hou, Jin; Gu, Yan; Zhang, Yi; Chen, Zhubo; Fan, Jia; Zhou, Weiping; Qiu, Shuangjian; Zhang, Yonghong; Dong, Tao; Li, Ning; Jiang, Zhengping; Zhu, Ha; Zhang, Qian; Ma, Yuanwu; Zhang, Lianfeng; Wang, Qingqing; Yu, Yizhi; Li, Nan; Cao, Xuetao

2018-04-19

Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119 + CD45 - CD71 + phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor artemin into the blood. Transforming growth factor β (TGF-β) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells' tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications. Copyright © 2018 Elsevier Inc. All rights reserved.

Escherichia coli clearance after splenic autotransplants

International Nuclear Information System (INIS)

Marques, R.G.; Petroianu, A.; Oliveira, M.B.N.; Bernardo-Filho, M.; Portela, M.C.

2002-01-01

Background: Splenic autotransplantation seems to be the only alternative for preservation of splenic tissue, after total splenectomy. The present study was carried out to analyze Escherichia coli depuration by mononuclear phagocyte system organs after total splenectomy and splenic autotransplantation. Methods: We utilized an experimental model including young and adult Wistar rats, of both sexes, submitted to total splenectomy and splenic autotransplantation. The evaluation method was intravenous inoculation of a suspension of Escherichia coli labeled with technetium-99m. We analyzed bacteria uptake by mononuclear phagocyte system organs and bacteria remnant in the bloodstream. Results: There was no difference between young and adult animals in bacteria uptake by mononuclear phagocyte system organs. In the comparison of groups, it was found out that the mean percent uptake by spleen and liver of animals in the control group was higher than that observed for animals with splenic implants. However, bacteria uptake in the lung was higher in the splenic implant group than in the control group. Although spleen bacteria uptake in the control group animals has been higher than that of animals in the splenic implant group, the remnant bacteria in the bloodstream was similar. Animals submitted to isolated total splenectomy showed higher bacteria remnant in the bloodstream than animals of the control group or the group submitted to total splenectomy combined with splenic autotransplantation. Conclusion: Our results indicate that autogenous splenic implant is efficacious in bacteria depuration in rats, by means of their macrophages phagocytosis. In addition, it does not modify bacteria removal function of liver and lung

CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses.

Science.gov (United States)

Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J

2018-05-15

Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.

Studies on the control mechanism and the degenerative immune function of dendritic cells using radiation

Energy Technology Data Exchange (ETDEWEB)

Yee, Sung Tae; Kim, Jong Jin; Choi, Ji Na; Park, Jung Eun; Jeong, Young Ran [Sunchon National University, Sunchon (Korea, Republic of)

2010-05-15

Dendritic cells are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and costimulatory molecule expression of spleen or bone marrow-derived CD11c{sup +} DCs of C57BL/6 mice. In the first year, we compared various function of dendritic cells isolated from young and gamma-irradiated 57BL/6 mice(5 weeks after {gamma}-radiation) for the development of aging models using radiation. In the second year, we also compared the function of spleen- and bone marrow-derived dendritic cells of young(2-3 months) and old(23-24 months) 57BL/6 mice. And we studied the differences of spleen- and bone marrow-derived dendritic cells of young and gamma-irradiated 57BL/6 mice(2, 4, 6 months after {gamma}-radiation) for the development of aging models in third year. And we obtained various differences between spleen- and bone marrow-derived dendritic cells of normal and old(23-24 months) or {gamma}-irradiated 57BL/6 mice. It is possible to use our results as age-associated model for modulation of the declined immunity and hematopoiesis for treatment of cancer, adult diseases and stress in aging. Such studies on the mechanism of aging model would further lead to new avenues for the development of functional foods which effect such as pathogenesis, inflammatory and autoimmune disorders. It will contributed to activation of related industry conforming quality and diversity of radiation industry. The techniques developed in our research may provide novel therapeutic modalities for age-associated immune dysfunctions

Maraba MG1 Virus Enhances Natural Killer Cell Function via Conventional Dendritic Cells to Reduce Postoperative Metastatic Disease

Science.gov (United States)

Zhang, Jiqing; Tai, Lee-Hwa; Ilkow, Carolina S; Alkayyal, Almohanad A; Ananth, Abhirami A; de Souza, Christiano Tanese; Wang, Jiahu; Sahi, Shalini; Ly, Lundi; Lefebvre, Charles; Falls, Theresa J; Stephenson, Kyle B; Mahmoud, Ahmad B; Makrigiannis, Andrew P; Lichty, Brian D; Bell, John C; Stojdl, David F; Auer, Rebecca C

2014-01-01

This study characterizes the ability of novel oncolytic rhabdoviruses (Maraba MG1) to boost natural killer (NK) cell activity. Our results demonstrate that MG1 activates NK cells via direct infection and maturation of conventional dendritic cells. Using NK depletion and conventional dendritic cells ablation studies in vivo, we established that both are required for MG1 efficacy. We further explored the efficacy of attenuated MG1 (nonreplicating MG1-UV2min and single-cycle replicating MG1-Gless) and demonstrated that these viruses activate conventional dendritic cells, although to a lesser extent than live MG1. This translates to equivalent abilities to remove tumor metastases only at the highest viral doses of attenuated MG1. In tandem, we characterized the antitumor ability of NK cells following preoperative administration of live and attenuated MG1. Our results demonstrates that a similar level of NK activation and reduction in postoperative tumor metastases was achieved with equivalent high viral doses concluding that viral replication is important, but not necessary for NK activation. Biochemical characterization of a panel of UV-inactivated MG1 (2–120 minutes) revealed that intact viral particle and target cell recognition are essential for NK cell–mediated antitumor responses. These findings provide mechanistic insight and preclinical rationale for safe perioperative virotherapy to effectively reduce metastatic disease following cancer surgery. PMID:24695102

Immune responses of dendritic cells after acquiring antigen from apoptotic hepatocholangioma cells caused by γ-ray

International Nuclear Information System (INIS)

Wu Gang; Gu Hongguang; Han Benli; Pei Xuetao

2002-01-01

Objective: To investigate the induction of cytotoxic T lymphocytes (CTLs) in antitumor responsiveness and therapeutic effects after dendritic cells (DCs) acquired antigen from apoptotic hepatocholangioma cells. Methods: DCs from blood mononuclear cells that maintain the characteristics of immaturity-anti-gen-capturing and-processing capacity were established in vitro by using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Then, apoptosis in hepatocholangioma cells was induced with γ-radiation. The experimental groups included (1) co-culture of DCs, and apoptotic cancer cells and T cells; (2) co-culture of DCs necrotic cancer cells and T cells; (3) co-culture of DCs-cultured cancer cell and T cells. These cells were co-cultured for 7 days. DCs and T cell were enriched separately. Finally, antitumor response test was carried out. Results: These cells had typical dendritic morphology, expressed high levels of CD1a, B7 and acquired antigen from apoptotic cells caused by γ-rays and induced an increased T cell-stimulatory capacity in MLR. Conclusions: DCs obtained from blood mononuclear cells using GM-CSF and IL-4 and DCs can efficiently present antigen driven from apoptotic cells caused by γ-rays and induce T cells increasing obviously. It can probably become an effective approach of DC transduction with antigen

A Rare Case of Retroperitoneal Follicular Dendritic Cell Sarcoma Identified by 99mTc-HYNIC-TOC SPECT/CT.

Science.gov (United States)

Li, Yi; Xu, Xiaoping; Xu, Junyan; Huang, Dan

2018-05-31

Follicular dendritic cell sarcoma is a very rare neoplasm, which is not lymphoma, but originates from a type of immune cells called follicular dendritic cells. We presented a 37-year-old woman who has suffered from obstructive jaundice, weight loss and right upper abdominal pain for 2 months. The contrast CT revealed masses located in the region of pancreatic head and lots of enlarged retroperitoneal lymph nodes, both of which were enhanced on the artery phase of CT images. Meanwhile, Tc-HYNIC-TOC SPECT/CT revealed high activity in the corresponding lesions. After biopsy, the masses were pathologically confirmed as retroperitoneal follicular dendritic cell sarcoma.

Computed tomography of splenic trauma

Energy Technology Data Exchange (ETDEWEB)

Jeffrey, R.B.; Laing, F.C.; Federle, M.P.; Goodman, P.C.

1981-12-01

Fifty patients with abdominal trauma and possible splenic injury were evaluated by computed tomography (CT). CT correctly diagnosed 21 of 22 surgically proved traumatic sesions of the spleen (96%). Twenty-seven patients had no evidence of splenic injury. This was confirmed at operation in 1 patient and clinical follow-up in 26. There were one false negative and one false positive. In 5 patients (10%), CT demonstrated other clinically significant lesions, including hepatic or renal lacerations in 3 and large retroperitoneal hematomas in 2. In adolescents and adults, CT is an accurate, noninvasive method of rapidly diagnosing splenic trauma and associated injuries. Further experience is needed to assess its usefulness in evaluating splenic injuries in infants and small children.

Computed tomography of splenic trauma

International Nuclear Information System (INIS)

Jeffrey, R.B.; Laing, F.C.; Federle, M.P.; Goodman, P.C.

1981-01-01

Fifty patients with abdominal trauma and possible splenic injury were evaluated by computed tomography (CT). CT correctly diagnosed 21 of 22 surgically proved traumatic sesions of the spleen (96%). Twenty-seven patients had no evidence of splenic injury. This was confirmed at operation in 1 patient and clinical follow-up in 26. There were one false negative and one false positive. In 5 patients (10%), CT demonstrated other clinically significant lesions, including hepatic or renal lacerations in 3 and large retroperitoneal hematomas in 2. In adolescents and adults, CT is an accurate, noninvasive method of rapidly diagnosing splenic trauma and associated injuries. Further experience is needed to assess its usefulness in evaluating splenic injuries in infants and small children

Splenic microenvironment and self recognition as factors in allograft rejection in rats. A study using indium-111-labeled cells

International Nuclear Information System (INIS)

Pollak, R.; Blanchard, J.M.; Lazda, V.A.

1986-01-01

Splenectomy facilitates organ allograft survival in some rat strains, and in weak donor-recipient histoincompatible pairs. We have found using a heart spleen twin graft model, using ACI rats as recipients and Lewis rats as donors, that the transplanted heart will survive in most recipients after delayed host splenectomy. The presence of a viable mass of splenic tissue will allow rejection to proceed only when the transplanted spleen is of host origin, and not when it comes from the donor (i.e., when it is allogeneic). The use of 111In-labeled cells has allowed us to show that lymphocyte traffic and trapping is markedly altered in the transplanted allogeneic spleens, when compared with control transplanted syngeneic spleens. Thus, despite the presence of the splenic ''microenvironment,'' cardiac allograft rejection does not occur in the absence of syngeneic splenic tissue. We conclude that the role of the spleen in the immune response is to facilitate the recognition of self and the acquisition of alloreactivity in weak responder rat strains and donor-recipient pairs

Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy

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Andy Petroianu

Full Text Available OBJECTIVE: To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy. METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative and peripheral blood (immediately pre and postoperative periods. RESULTS: the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood. CONCLUSION: hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy.

Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

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Fabrice Ango

2008-04-01

Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology.

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Guy eElston

2014-08-01

Full Text Available Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1 prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE and granular prefrontal cortex (gPFC; Brodmann’s area 12 grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the use it or lose it notion of synaptic reinforcement may speak to only part of the story, use it but you still might lose it may be just as prevalent in the cerebral cortex.

An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

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Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

2010-01-01

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

Dynein and EFF-1 control dendrite morphology by regulating the localization pattern of SAX-7 in epidermal cells.

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Zhu, Ting; Liang, Xing; Wang, Xiang-Ming; Shen, Kang

2017-12-01

Our previous work showed that the cell adhesion molecule SAX-7 forms an elaborate pattern in Caenorhabditis elegans epidermal cells, which instructs PVD dendrite branching. However, the molecular mechanism forming the SAX-7 pattern in the epidermis is not fully understood. Here, we report that the dynein light intermediate chain DLI-1 and the fusogen EFF-1 are required in epidermal cells to pattern SAX-7. While previous reports suggest that these two molecules act cell-autonomously in the PVD, our results show that the disorganized PVD dendritic arbors in these mutants are due to the abnormal SAX-7 localization patterns in epidermal cells. Three lines of evidence support this notion. First, the epidermal SAX-7 pattern was severely affected in dli-1 and eff-1 mutants. Second, the abnormal SAX-7 pattern was predictive of the ectopic PVD dendrites. Third, expression of DLI-1 or EFF-1 in the epidermis rescued both the SAX-7 pattern and the disorganized PVD dendrite phenotypes, whereas expression of these molecules in the PVD did not. We also show that DLI-1 functions cell-autonomously in the PVD to promote distal branch formation. These results demonstrate the unexpected roles of DLI-1 and EFF-1 in the epidermis in the control of PVD dendrite morphogenesis. © 2017. Published by The Company of Biologists Ltd.

Lactobacillus delbrueckii subsp lactis CIDCA 133 modulates response of human epithelial and dendritic cells infected with Bacillus cereus.

Science.gov (United States)

Rolny, I S; Tiscornia, I; Racedo, S M; Pérez, P F; Bollati-Fogolín, M

2016-11-30

It is known that probiotic microorganisms are able to modulate pathogen virulence. This ability is strain dependent and involves multiple interactions between microorganisms and relevant host's cell populations. In the present work we focus on the effect of a potentially probiotic lactobacillus strain (Lactobacillus delbrueckii subsp. lactis CIDCA 133) in an in vitro model of Bacillus cereus infection. Our results showed that infection of intestinal epithelial HT-29 cells by B. cereus induces nuclear factor kappa B (NF-κB) pathway. Noteworthy, the presence of strain L. delbrueckii subsp.lactis CIDCA 133 increases stimulation. However, B. cereus-induced interleukin (IL)-8 production by epithelial cells is partially abrogated by L. delbrueckii subsp. lactis CIDCA 133. These findings suggest that signalling pathways other than that of NF-κB are involved. In a co-culture system (HT-29 and monocyte-derived dendritic cells), B. cereus was able to translocate from the epithelial (upper) to the dendritic cell compartment (lower). This translocation was partially abrogated by the presence of lactobacilli in the upper compartment. In addition, infection of epithelial cells in the co-culture model, led to an increase in the expression of CD86 by dendritic cells. This effect could not be modified in the presence of lactobacilli. Interestingly, infection of enterocytes with B. cereus triggers production of proinflammatory cytokines by dendritic cells (IL-8, IL-6 and tumour necrosis factor alpha (TNF-α)). The production of TNF-α (a protective cytokine in B. cereus infections) by dendritic cells was increased in the presence of lactobacilli. The present work demonstrates for the first time the effect of L. delbrueckii subsp. lactis CIDCA 133, a potentially probiotic strain, in an in vitro model of B. cereus infection. The presence of the probiotic strain modulates cell response both in infected epithelial and dendritic cells thus suggesting a possible beneficial effect of

The role of dendritic cells in cancer

DEFF Research Database (Denmark)

Hansen, Morten; Andersen, Mads Hald

2017-01-01

Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8+ T-cells and Th1 helper CD4+ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when...... infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103+ DCs, which have been shown to be experts in cross-priming and the induction...... of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E2 and β-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized...

Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation

Directory of Open Access Journals (Sweden)

Jessberger Sebastian

2006-11-01

Full Text Available Abstract Background In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. Results We found that (1 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2 the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3 positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. Conclusion These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed by dendritic cells.

NARCIS (Netherlands)

Hartgers, F.C.; Vissers, J.L.M.; Looman, M.W.G.; Zoelen, C. van; Huffine, C.; Figdor, C.G.; Adema, G.J.

2000-01-01

Dendritic cells (DC) are unique in their ability to present antigen to naive T cells, and therefore play a central role in the initiation of immune responses. Characterization of DC-specific genes may help to unravel the mechanism underlying their potent antigen presenting capacity. Here we describe

Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells.

Science.gov (United States)

Jung, Tae-Young; Pham, Thanh Nhan Nguyen; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

2010-09-25

Ursolic acid is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cell maturation is critical for the induction of Ag-specific T-lymphocyte response and may be essential for the development of human vaccine relying on T cell immunity. In this study, we investigated that the effect of Ursolic acid on the phenotypic and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells harvested on day 8 were examined using functional assay. The expression levels of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 on Ursolic acid-primed dendritic cells was slightly enhanced. Ursolic acid dose-dependently enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte reaction, as measured by T cell proliferation. The production of IL-12p70 induced by Ursolic acid-primed dendritic cells was inhibited by the anti-Toll-like receptor-2 (TLR2) mAb and anti-TLR4 mAb. Moreover, Ursolic acid-primed dendritic cells expressed levels of mRNA coding for both TLR2 and TLR4. The majority of cells produced considerable interferon-gamma (IFN-gamma), but also small amounts of interleukin (IL-4)-4. Ursolic acid-primed dendritic cells have an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that Ursolic acid modulates human dendritic cells function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR2 and/or TLR4, and may be used on dendritic cells-based vaccines for cancer immunotherapy. 2010 Elsevier B.V. All rights reserved.

Morphophysiological changes in the splenic extracellular matrix of Leishmania infantum-naturally infected dogs is associated with alterations in lymphoid niches and the CD4+ T cell frequency in spleens.

Directory of Open Access Journals (Sweden)

Aurea Virginia Andrade da Silva

2018-04-01

Full Text Available The spleen is one of the main affected organs in canine visceral leishmaniasis (CVL. Disorganization of the splenic white pulp (SWP has been associated with immunosuppression and disease progression. This study aims to assess structural and cellular changes in the splenic extracellular matrix of dogs with CVL, correlating these changes with the parasite load and clinical signs. Splenic fragments were collected from 41 naturally infected animals for parasite load quantification by quantitative PCR, histopathological analysis and immunohistochemistry for CD3+, CD4+, and CD8+ T cells; CD21+ B cells; Ki-67+, IFN-γ+, and IL-10+ cells; and the MMP-9 and ADAM-10 enzymes. Laminin, collagen and fibronectin deposition were also evaluated. The animals were grouped according to the level of SWP organization. SWP disorganization was accompanied by a reduction in the quantity of lymphoid follicles/mm2 (p > 0.0001. Animals with moderate to intense SWP disorganization showed more clinical signs (p = 0.021, higher laminin (p = 0.045 and collagen deposition (p = 0.036, higher MMP-9 expression (p = 0.035 and lower numbers of CD4+ T cells (p = 0.027 in the spleen than the animals with organized SWP. These data suggest that splenic structure and function are drastically altered and compromised during CVL.

A Simulation Study on the Effects of Dendritic Morphology on Layer V Prefontal Pyramidal Cell Firing Behavior

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Maria ePsarrou

2014-09-01

Full Text Available Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1 repetitive action potentials (Regular Spiking - RS, and (2 an initial cluster of 2-5 action potentials with short ISIs followed by single spikes (Intrinsic Bursting - IB. A correlation between firing behavior and dendritic morphology has recently been reported. In this work we use computational modeling to investigate quantitatively the effects of the basal dendritic tree morphology on the firing behavior of 112 three-dimensional reconstructions of layer V PFC rat pyramidal cells. Particularly, we focus on how different morphological (diameter, total length, volume and branch number and passive (Mean Electrotonic Path length features of basal dendritic trees shape somatic firing when the spatial distribution of ionic mechanisms in the basal dendritic trees is uniform or non-uniform. Our results suggest that total length, volume and branch number are the best morphological parameters to discriminate the cells as RS or IB, regardless of the distribution of ionic mechanisms in basal trees. The discriminatory power of total length, volume and branch number remains high in the presence of different apical dendrites. These results suggest that morphological variations in the basal dendritic trees of layer V pyramidal neurons in the PFC influence their firing patterns in a predictive manner and may in turn influence the information processing capabilities of these neurons.

Primary splenic torsion in a Boston terrier

International Nuclear Information System (INIS)

Ohta, H.; Takagi, S.; Murakami, M.; Sasaki, N.; Yoshikawa, M.; Nakamura, K.; Hwang, S.J.; Yamasaki, M.; Takiguchi, M.

2009-01-01

A 7-year-old female Boston terrier was referred to Hokkaido University Veterinary Teaching Hospital with a history of hemoglobinuria and anemia for several days. Abdominal radiographs showed splenomegaly, and ultrasonography revealed a hypoechoic splenic parenchyma with interspersed linear echoes consistent with the ultrasonographic appearance of splenic torsion. Ultrasonography and computed tomography (CT) indicated a C-shaped spleen. Exploratory laparotomy confirmed the diagnosis of splenic torsion. A splenectomy was performed, and the dog recovered well without complications. This is the first report of splenic torsion in Boston terriers, and the usefulness of ultrasonographic and CT findings of the splenic torsion was also confirmed

Primary splenic torsion in a Boston terrier.

Science.gov (United States)

OHTA, Hiroshi; TAKAGI, Satoshi; MURAKAMI, Masahiro; SASAKI, Noboru; YOSHIKAWA, Muneyoshi; NAKAMURA, Kensuke; HWANG, Shiang-Jyi; YAMASAKI, Masahiro; TAKIGUCHI, Mitsuyoshi

2009-11-01

A 7-year-old female Boston terrier was referred to Hokkaido University Veterinary Teaching Hospital with a history of hemoglobinuria and anemia for several days. Abdominal radiographs showed splenomegaly, and ultrasonography revealed a hypoechoic splenic parenchyma with interspersed linear echoes consistent with the ultrasonographic appearance of splenic torsion. Ultrasonography and computed tomography (CT) indicated a C-shaped spleen. Exploratory laparotomy confirmed the diagnosis of splenic torsion. A splenectomy was performed, and the dog recovered well without complications. This is the first report of splenic torsion in Boston terriers, and the usefulness of ultrasonographic and CT findings of the splenic torsion was also confirmed.

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

OpenAIRE

Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

Characterization of monocyte-derived dendritic cells maturated with IFN-alpha

DEFF Research Database (Denmark)

Svane, I M; Nikolajsen, K; Walter, M R

2006-01-01

Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required......, maturation with IFN-alpha has only a small effect on induction of autologous T-cell stimulatory capacity of the DC. However, an increase in DC allogeneic T-cell stimulatory capacity was observed. These data suggest that IFN-alpha has a potential as a maturation agent used in DC-based cancer vaccine trials...

Hematological and splenic Doppler ultrasonographic changes in dogs sedated with acepromazine or xylazine.

Science.gov (United States)

Sutil, Dienifer V; Mattoso, Cláudio R S; Volpato, Julieta; Weinert, Nádia C; Costa, Ádson; Antunes, Rozyanne R; Muller, Thiago R; Beier, Suzane L; Tochetto, Ronise; Comassetto, Felipe; Saito, Mere E

2017-07-01

To evaluate the onset and duration of hematological changes and the use of Doppler ultrasound (spleen) in dogs sedated with acepromazine or xylazine. Clinical study. A total of 24 mixed breed dogs aged 1-4 years and weighing 15-25 kg. Dogs were randomly distributed into two groups: acepromazine group (AG) which were administered acepromazine (0.05 mg kg -1 ) intramuscularly and xylazine group (XG) administered xylazine (0.5 mg kg -1 ) intramuscularly. Sonographic evaluations (morphologic and hemodynamic splenic vascularization) and hematologic tests were performed before drug administration (baseline) and 5, 15, 30, 60, 120, 240, 360, 480 and 720 minutes after drug administration. A significant reduction occurred in erythrogram variables in AG at 15-720 minutes corresponding with a significant enlargement of the spleen. In XG, a significant reduction was observed in the erythrogram variables at 30-60 minutes without a significant enlargement of the spleen. Hilar diameter did not change over time in either group. Flow alterations were found only in the splenic artery in AG, with a decreased final diastolic velocity observed at 60-120 minutes. Administration of acepromazine resulted in decreased red blood cell count, hemoglobin, packed cell volume and an increased diameter of the spleen. Xylazine administration resulted in similar hematologic changes but of smaller magnitude and duration and without splenic changes. The absence of significant changes in the Doppler flow parameters of the splenic artery and vein and the hilar diameter suggests that the splenomegaly that was observed in AG was not due to splenic vasodilation. No splenic sequestration occurred after xylazine administration. The results indicate that acepromazine decreases the erythrocyte concentrations by splenic erythrocyte sequestration and concomitant splenomegaly. Xylazine can cause slight hematologic changes, but without splenic changes. Copyright © 2017 Association of Veterinary

Immunodetection of myeloid and plasmacytoid dendritic cells in mammary carcinomas of female dogs

Directory of Open Access Journals (Sweden)

Mayara C. Rosolem

2015-11-01

Full Text Available ABSTRACT: Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group, in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment.

Treatment outcomes and prognostic factors of feline splenic mast cell tumors: A multi-institutional retrospective study of 64 cases.

Science.gov (United States)

Evans, B J; O'Brien, D; Allstadt, S D; Gregor, T P; Sorenmo, K U

2018-03-01

Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited information on treatment outcomes of cats with this disease. This retrospective study evaluated treatment outcomes in 64 cats with splenic MCT. Cats were categorized into the following treatment groups: splenectomy (A, n = 20); splenectomy with chemotherapy (B, n = 20); chemotherapy alone (C, n = 15); or supportive care (D, n = 9). Median tumor specific survival (MTSS) was: 856, 853, 244, 365 days for groups A, B, C, and D, respectively. The MTSS was not significantly different between the 4 groups. However, comparing cats that had splenectomy (A and B) versus those that did not (C and D), the MTSS was 856 and 342 days, respectively (p=0.008). None of the prognostic factors analyzed significantly influenced survival. Splenectomy (+/- chemotherapy) significantly prolongs survival in cats with mast cell tumors. The role of chemotherapy remains unknown. © 2017 John Wiley & Sons Ltd.

Targeting Radiation Therapy for Developing Dendritic Cell Based Immunotherapy of Metastatic Prostate Cancer

National Research Council Canada - National Science Library

Chakravarty, Prabir K

2006-01-01

.... The hypothesis was tested using a murine prostate cancer model, RM-1. The study showed that irradiation induces apoptosis and the irradiated tumor cells were able to activate dendritic cells and stimulate tumor specific immune response in vitro...

The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells

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Giulia Chiaruttini

2016-03-01

Full Text Available Interleukin-12 (IL-12, produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells.

In situ concentration cartography in the neighborhood of dendrites growing in lithium/polymer-electrolyte/lithium cells

Energy Technology Data Exchange (ETDEWEB)

Brissot, C.; Rosso, M.; Chazalviel, J.N.; Lascaud, S.

1999-12-01

The authors report on three different in situ and ex situ concentration measurement methods in symmetric lithium/polymer-electrolyte/lithium cells. The results were examined on the basis of a simple calculation of ionic concentration within the electrolyte, in the case where no dendrite is observed, this calculation accounts quantitatively for all experimental results. In the case of dendritic growth, the authors can measure the concentration distribution around the dendrites; this permits correlation of the active parts of the electrodes and of the growing dendrites with local ionic depletion in the vicinity of these active parts.

Crosstalk between T lymphocytes and dendritic cells.

Science.gov (United States)

Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle

2012-01-01

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique property of inducing priming and differentiation of naïve CD4+ and CD8+ T cells into helper and cytotoxic effectors. Their efficiency is due to their unique ability to process antigen, express costimulatory molecules, secrete cytokines, and migrate to tissues or lymphoid organs to prime T cells. DCs also play an important role in T-cell peripheral tolerance. There is ample evidence that the DC ability to present antigens is regulated by CD4+ helper T cells. Indeed, interactions between surface receptors and ligands expressed respectively by T cells and DCs, as well as T-cell-derived cytokines modify DC functions. This T-cell-induced modification of DCs has been called "education" or "licensing." This intimate crosstalk between DCs and T lymphocytes is key in establishing appropriate adaptive immune responses. It requires cognate interactions between T lymphocytes and DCs, which are organized in time and space by structures called immunological synapses. Here we discuss the particular aspects of immunological synapses formed between T cells and DCs and the role these organized interactions have in T-cell-DC crosstalk.

Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

Directory of Open Access Journals (Sweden)

Simone P. Sittig

2015-12-01

Full Text Available Dendritic cell (DC-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.

Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

Science.gov (United States)

Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

2014-01-01

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells

NARCIS (Netherlands)

van der Aar, Angelic M. G.; Sibiryak, Darya S.; Bakdash, Ghaith; van Capel, Toni M. M.; van der Kleij, Hanneke P. M.; Opstelten, Dirk-Jan E.; Teunissen, Marcel B. M.; Kapsenberg, Martien L.; de Jong, Esther C.

2011-01-01

Background: The vitamin D metabolite 1,25(OH) 2D3 (VitD3) is a potent immunosuppressive drug and, among others, is used for topical treatment of psoriasis. A proposed mechanism of VitD3-mediated suppression is priming of dendritic cells (DCs) to induce regulatory T (Treg) cells. Objective:

Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

DEFF Research Database (Denmark)

Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

2015-01-01

Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 defici...

Splenic trauma: Is splenectomy redundant?

Directory of Open Access Journals (Sweden)

S Tandon

2013-01-01

Full Text Available 41 year old male, serving air warrior sustained blunt abdominal trauma, CECT revealed grade III splenic injury. He was managed conservatively with good clinical outcome. Conservatism is the new approach to splenic trauma.

CT assessment of normal splenic size in children

International Nuclear Information System (INIS)

Prassopoulos, P.; Cavouras, D.

1994-01-01

The size of the normal spleen was estimated by CT in 153 children, examined with indication unrelated to splenic disease. In each patient the width, thickness, length and volume of the spleen were calculated. Measurements were also normalized to the transverse diameter of the body of the first lumbar vertebra. The spleen underwent significant growth during the first 4 years of life and reached maximum size at the age of 13. There were no differences in splenic volume between boys and girls. Splenic thickness correlated best with normal splenic volume. The strongest correlation was also found between splenic thickness and volume in a group of 45 children with clinically evident splenomegaly. Splenic thickness, an easy-to-use measurement, may be employed in everyday practice to represent splenic volume on CT. (orig.)

Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells

NARCIS (Netherlands)

Everts, Bart; Amiel, Eyal; van der Windt, Gerritje J. W.; Freitas, Tori C.; Chott, Robert; Yarasheski, Kevin E.; Pearce, Erika L.; Pearce, Edward J.

2012-01-01

TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents

acquisition of antigens by airway dendritic cells. do we know enough?

African Journals Online (AJOL)

kiama

These responses are thought to be mediated via dendritic cells, which are located in the basal ... delivery to the DC in the airways. Are the ... feature of inflammatory airway disease, like asthma .... drug delivery and as vectors in delivery of.

Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin.

Science.gov (United States)

Bennett, Jared R; Lateef, Zabeen; Fleming, Stephen B; Mercer, Andrew A; Wise, Lyn M

2016-02-02

Orf virus (ORFV) is a zoonotic parapoxvirus that causes pustular dermatitis of sheep, and occasionally humans. Despite causing sustained infections, ORFV induces only a transient increase in pro-inflammatory signalling and the trafficking of innate immune cells within the skin seems to be impaired. An explanation for this tempered response to ORFV infection may lie in its expression of a homolog of the anti-inflammatory cytokine, interleukin (IL)-10. Using a murine model in which inflammation was induced by bacterial lipopolysaccharide, we examined the effects of the ORFV-IL-10 protein on immune cell trafficking to and from the skin. ORFV-IL-10 limited the recruitment of blood-derived Gr-1(int)/CD11b(int) monocytes, CD11c(+ve)/MHC-II(+ve) dendritic cells and c-kit(+ve)/FcεR1(+ve) mature mast cells into inflamed skin. ORFV-IL-10 also suppressed the activation of CD11c(+ve)/MHC-II(+ve) dendritic cells within the skin, reducing their trafficking to the draining lymph node. These findings suggest that expression of IL-10 by ORFV may contribute to the impaired trafficking of innate immune cells within infected skin. Copyright © 2015 Elsevier B.V. All rights reserved.

Determinants of splenectomy in splenic injuries following blunt ...

African Journals Online (AJOL)

Introduction. The management of splenic injuries has shifted from splenectomy to splenic preservation owing to the risk of overwhelming post-splenectomy infection (OPSI). This study aimed to identify the factors that determine splenectomy in patients with isolated splenic injuries, with a view to increasing the rate of splenic ...

Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

Science.gov (United States)

2013-07-01

transfected with RNA. NatBiotech. 1998;16:364-369. 20. Heiser A, Dahm P, Yancey DR, et al. Human dendritic cells transfected with RNA encoding prostate...specific antigen stimulate prostate-specific CTL responses in vitro. J Immunol. 2000;164(10):5508-5514. 21. Heiser A, Maurice MA, Yancey DR...primary and metastatic tumors. Cancer Res. 2001;61(8):3388-3393. 22. Heiser A, Coleman D, Dannull J, et al. Autologous dendritic cells transfected

DMPD: Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediators. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available l) (.csml) Show Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediator...egulation of dendritic cell-derivedinflammatory mediators. Authors Harizi H, Gualde N. Publication Cell Mol ...16978535 Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derivedinflammatory mediat...ors. Harizi H, Gualde N. Cell Mol Immunol. 2006 Aug;3(4):271-7. (.png) (.svg) (.htm

Impact of Splenic Artery Embolization on the Success Rate of Nonoperative Management for Blunt Splenic Injury

International Nuclear Information System (INIS)

Vlies, C. H. van der; Hoekstra, J.; Ponsen, K. J.; Reekers, J. A.; Delden, O. M. van; Goslings, J. C.

2012-01-01

Introduction: Nonoperative management (NOM) has become the treatment of choice for hemodynamically stable patients with blunt splenic injury. Results of outcome after NOM are predominantly based on large-volume studies from level 1 trauma centers in the United States. This study was designed to assess the results of NOM in a relatively low-volume Dutch level 1 trauma center. Methods: An analysis of a prospective trauma registry was performed for a 6-year period before (period 1) and after the introduction and implementation of splenic artery embolization (SAE) (period 2). Primary outcome was the failure rate of initial treatment. Results: A total of 151 patients were reviewed. An increased use of SAE and a reduction of splenic operations during the second period was observed. Compared with period 1, the failure rate after observation in period 2 decreased from 25% to 10%. The failure rate after SAE in period 2 was 18%. The splenic salvage rate (SSR) after observation increased from 79% in the first period to 100% in the second period. During the second period, all patients with failure after observation were successfully treated with SAE. The SSR after SAE in periods 1 and 2 was respectively 100% and 86%. Conclusions: SAE of patients with blunt splenic injuries is associated with a reduction in splenic operations. The failure and splenic salvage rates in this current study were comparable with the results from large-volume studies of level 1 trauma centers. Nonoperative management also is feasible in a relatively low-volume level 1 trauma center outside the United States.

Targeting CD4(+) T-Helper Cells Improves the Induction of Antitumor Responses in Dendritic Cell-Based Vaccination

NARCIS (Netherlands)

Aarntzen, Erik H. J. G.; de Vries, I. Jolanda M.; Lesterhuis, W. Joost; Schuurhuis, Danita; Jacobs, Joannes F. M.; Bol, Kalijn; Schreibelt, Gerty; Mus, Roel; de Wilt, Johannes H. W.; Haanen, John B. A. G.; Schadendorf, Dirk; Croockewit, Alexandra; Blokx, Willeke A. M.; van Rossum, Michelle M.; Kwok, William W.; Adema, Gosse J.; Punt, Cornelis J. A.; Figdor, Carl G.

2013-01-01

To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC

Loss of Ia-bearing splenic adherent cells after whole body ultraviolet irradiation

International Nuclear Information System (INIS)

Letvin, N.L.; Nepom, J.T.; Greene, M.I.; Benacerraf, B.; Germain, R.N.

1980-01-01

Daily uv irradiation of mice results in a marked decrease in the antigen-presenting capability of SAC from these mice after 1 wk of uv exposure. To directly examine this cell population, we developed a technique for purifying SAC that involves passing mouse splenocytes through two cycles of glass adherence with an intervening incubation on rabbit anti-mouse Ig-coated dishes. SAC from externally uv irradiated mice prepared by this method, when pulsed with antigen, activate primed T cells to proliferate much less efficiently than SAC from normal mice. Both the proportion and absolute number of Ia-bearing cells in this purified SAC population from uv irradiated mice are considerably smaller than that seen in similarly prepared populations from normal mice. Previous adjuvant immunization was shown to override functional defects elicited by external uv irradiation. This demonstration of a uv irradiation induced selective loss of Ia bearing splenic adherent cells and the functional consequences of this loss provide further evidence for the importance of Ia-bearing accessory cells in antigen presentation of T dependent antigens, and provides insight into the origin of the immunologic defects induced by whole body uv irradiation

Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.

Science.gov (United States)

Costa, Vivian Vasconcelos; Ye, Weijian; Chen, Qingfeng; Teixeira, Mauro Martins; Preiser, Peter; Ooi, Eng Eong; Chen, Jianzhu

2017-08-01

Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo , identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control

EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.

Science.gov (United States)

Squadrito, Mario Leonardo; Cianciaruso, Chiara; Hansen, Sarah K; De Palma, Michele

2018-03-01

We describe a lentivirus-encoded chimeric receptor, termed extracellular vesicle (EV)-internalizing receptor (EVIR), which enables the selective uptake of cancer-cell-derived EVs by dendritic cells (DCs). The EVIR enhances DC presentation of EV-associated tumor antigens to CD8 + T cells primarily through MHCI recycling and cross-dressing. EVIRs should facilitate exploring the mechanisms and implications of horizontal transfer of tumor antigens to antigen-presenting cells.

T cell motility as modulator of interactions with dendritic cells

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Jens Volker Stein

2015-11-01

Full Text Available It is well established that the balance of costimulatory and inhibitory signals during interactions with dendritic cells (DCs determines T cell transition from a naïve to an activated or tolerant/anergic status. While many of these molecular interactions are well reproduced in reductionist in vitro assays, the highly dynamic motility of naïve T cells in lymphoid tissue acts as an additional lever to fine-tune their activation threshold. T cell detachment from DCs providing suboptimal stimulation allows them to search for DCs with higher levels of stimulatory signals, while storing a transient memory of short encounters. In turn, adhesion of weakly reactive T cells to DCs presenting pMHC with low affinity is prevented by lipid mediators. Finally, controlled recruitment of CD8+ T cells to cognate DC – CD4+ T cell clusters shapes memory T cell formation and the quality of the immune response. Dynamic physiological lymphocyte motility therefore constitutes a mechanism to mitigate low avidity T cell activation and to improve the search for optimal DCs, while contributing to peripheral tolerance induction in the absence of inflammation.

Clec9a-Mediated Ablation of Conventional Dendritic Cells Suggests a Lymphoid Path to Generating Dendritic Cells In Vivo

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Johanna Salvermoser

2018-04-01

Full Text Available Conventional dendritic cells (cDCs are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired.

A PROSPECTIVE STUDY ON SPLENIC INJURY

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Palanivel Rajagopal

2017-04-01

Full Text Available BACKGROUND An injured spleen is a well-known entity to those involved in trauma care. The majority of individual with a splenic injury now receive nonoperative intervention and therapy. This shift from operative to nonoperative treatment over the past several decades is a tremendous success story in which clinical judgment and reason triumphed over standard surgical dogma. In emergency room, restoration of airway, breathing and circulation should be focussed on. A careful history is the most important one. Nevertheless, the severity of the splenic injury plays a dominant part in determining whether nonoperative management is appropriate or-if-not-whether splenorrhaphy or splenectomy will be the more appropriate surgical option. As a general rule, younger, healthier patients with lower grade splenic injuries and fewer associated injuries and comorbidities are usually managed nonoperatively or with splenic repair, whether unstable, actively bleeding patients with more severe splenic trauma and/or multiple associated injuries require splenectomy. The aim of the study is to evaluate- 1. The impact of blunt or penetrating abdominal trauma on spleen. 2. Various modes of injury. 3. Various modes of clinical presentation of cases. 4. The value of various available investigations employed. 5. The various methods of treatment. 6. The morbidity and mortality. MATERIALS AND METHODS This study was a prospective study of 20 cases of splenic injury admitted in the triage ward of Mahatma Gandhi Memorial Government Medical College Hospital, Trichy, over a period of 2 years from December 2014 to December 2016. Once the patient is admitted, the name, age, sex and mode of injury are noted. The time interval between splenic injury and admission and time interval between admission to hospital and surgery are recorded. After resuscitating the patient, all patients were subjected to careful clinical examination. RESULTS The total number of patients who had sustained

Preclinical Evaluation of Novel Dendritic Cell-Based Prostate Cancer Vaccines

Science.gov (United States)

2008-01-01

payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this...in melanoma patients is determined by their maturation state. Cancer Res 2003;63:12–7. 34. Nestle FO, Banchereau J, Hart D. Dendritic cells: on the

Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

Energy Technology Data Exchange (ETDEWEB)

Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

2010-05-14

Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells.

Science.gov (United States)

Verbrugghe, Phebe; Kujala, Pekka; Waelput, Wim; Peters, Peter J; Cuvelier, Claude A

2008-03-01

The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer's patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer's ring. Immunohistochemistry for clusterin in human Peyer's patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer's patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research.

Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis.

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Stella E Autenrieth

2012-02-01

Full Text Available Dendritic cells (DCs as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye. We used CD11c-diphtheria toxin (DT mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection.

MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

NARCIS (Netherlands)

Saeland, E.; Jong, de M.A.W.P.; Nabatov, A.; Kalay, H.; Kooijk, van Y.; Geijtenbeek, T.B.H.

2009-01-01

Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk,

GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells

Science.gov (United States)

Greter, Melanie; Helft, Julie; Chow, Andrew; Hashimoto, Daigo; Mortha, Arthur; Agudo-Cantero, Judith; Bogunovic, Milena; Gautier, Emmanuel L.; Miller, Jennifer; Leboeuf, Marylene; Lu, Geming; Aloman, Costica; Brown, Brian D.; Pollard, Jeffrey W.; Xiong, Huabao; Randolph, Gwendalyn J.; Chipuk, Jerry E.; Frenette, Paul S.; Merad, Miriam

2012-01-01

SUMMARY GM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103+ DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103+ and CD11b+ DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8+ T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8+ T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo. PMID:22749353

3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation

OpenAIRE

Okano, Takaichi; Saegusa, Jun; Nishimura, Keisuke; Takahashi, Soshi; Sendo, Sho; Ueda, Yo; Morinobu, Akio

2017-01-01

Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all i...

Con-nectin axons and dendrites.

Science.gov (United States)

Beaudoin, Gerard M J

2006-07-03

Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

Boron Affects Immune Function Through Modulation of Splenic T Lymphocyte Subsets, Cytokine Secretion, and Lymphocyte Proliferation and Apoptosis in Rats.

Science.gov (United States)

Jin, Erhui; Li, Shenghe; Ren, Man; Hu, Qianqian; Gu, Youfang; Li, Kui

2017-08-01

This study demonstrated the mechanisms of boron effects in a rat model and provided a scientific basis for the rational of boron use. These findings were achieved by investigating the effects of boron (10, 20, 40, 80, 160, 320, and 640 mg/L in drinking water or 1.5, 3, 6, 12, 24, 48, and 96 mg/kg BW) on rat serum immunoglobulins (IgGs), splenic cytokines, lymphocyte subsets, as well as on lymphocyte proliferation and apoptosis. Addition of 20 (3) and 40 (6) mg/L (mg/kg BW) of boron to drinking water significantly increased rat serum IgG concentrations, splenic IFN-γ and IL-4 expression as well as the number of splenic CD3 + , CD4 + and proliferating cell nuclear antigen (PCNA) + cells. Supplementation of drinking water with 40 mg/L (6 mg/kg BW) boron also markedly increased splenic IL-2 expression and the CD4 + /CD8 + cell ratio and reduced splenic CD8 + cell number. Supplementation with 80 mg/L (12 mg/kg BW) boron significantly increased CD3 + and PCNA + cell numbers (P boron markedly reduced the serum IgG concentrations; splenic IL-2 and IL-10 expression; the number of CD3 + , CD4 + and PCNA + cells; and increased the number of splenic CD8 + and caspase-3 + cells and promoted caspase-3 expression in CD3 + cells. In conclusion, these findings suggest that the supplementation of rat drinking water with 20(3) and 40(6) mg/L (mg/kg BW) boron can markedly enhance humoral and cellular immune functions, while boron concentrations above 320 mg/L (48 mg/kg BW) can have an inhibitory effect or even toxicity on immune functions. These results exhibit a U-shaped response characteristic of low and high doses of boron supplementation on immune function and imply that proper boron supplementation in food for humans and animals could be used as an immunity regulator.

Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

International Nuclear Information System (INIS)

Skvarc, Miha; Stubljar, David; Kopitar, Andreja Natasa; Jeverica, Samo; Tepes, Bojan; Kos, Janko; Ihan, Alojz

2013-01-01

The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

Splenic trauma management in relation to mode and grade

International Nuclear Information System (INIS)

Gangat, S.A.; Khaskhali, A.A.; Memon, I.A.

2008-01-01

To study the prevalence and management of splenic trauma in relation to its mode and grade. All cases admitted in emergency with abdominal trauma and splenic injury. The data of all the patients who had splenic trauma was entered on a proforma and analyzed. A total of 44 patients with ages between 20-40 years presented with splenic injury; 32(72.7%) were male. The commonest mode of splenic trauma was blunt abdominal injury (50%), and most (47%) patients had Grade- III injury. Splenectomy was carried out in 84% patients, while 9% underwent splenic salvage. Seven (15.9%) patients with splenectomy died in the series. Splenic injury was mostly caused by blunt abdominal trauma. Proper assessment of the grade of injury at the time of laparotomy resulted in more splenic salvage procedures with decreased risk of complications. (author)

Chemokines: a new dendritic cell signal for T cell activation

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Christoph A Thaiss

2011-08-01

Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

Molecular characterization of dendritic cells operating at the interface of innate or acquired immunity.

NARCIS (Netherlands)

Figdor, C.G.

2003-01-01

Dendritic Cells (DC) are natural adjuvants able to elicit specific cellular interactions and priming of naive T cells at a mature stage of their differentiation. Recent genomic approaches helped defining DC or Langherans Cells (LC) in more molecular terms. DC-SIGN, the DC specific ICAM-3 grabbing

Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

Science.gov (United States)

2018-05-10

B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis.

Science.gov (United States)

Izumi, Gentaro; Koga, Kaori; Takamura, Masashi; Makabe, Tomoko; Nagai, Miwako; Urata, Yoko; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Fujii, Tomoyuki; Osuga, Yutaka

2017-01-01

To characterize peritoneal dendritic cells (DCs) in endometriosis and to clarify their role in its etiology. Experimental. University hospital. Sixty-three women (35 patients with endometriosis and 28 control women) who had undergone laparoscopic surgery. Peritoneal DCs from endometriosis and control samples were analyzed for the expression of cell surface markers. Monocyte-derived dendritic cells (Mo-DCs) were cultured with dead endometrial stromal cells (dESCs) to investigate changes in phagocytic activity and cytokine expression. Cell surface markers and cytokine expression and identification with the use of flow cytometry or reverse-transcription polymerase chain reaction (RT-PCR). Changes in cytokine expression and phagocytic activity of Mo-DCs cultured with dESCs and d-mannan were measured with the use of flow cytometry and RT-PCR. The proportion of mannose receptor (MR)-positive myeloid DC type 1 was higher in endometriosis samples than in control samples. The blocking of MR reduced phagocytosis of dESCs by Mo-DCs. Mo-DCs cultured with dESCs expressed higher levels of interleukin (IL) 1β and IL-6 than control samples. Peritoneal DCs in endometriosis tissue express high levels of MR, which promotes phagocytosis of dead endometrial cells and thereby contributes to the etiology of endometriosis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Large primary splenic cyst: A laparoscopic technique.

LENUS (Irish Health Repository)

Geraghty, M

2009-01-01

Splenic cysts are rare lesions with around 800 cases reported in the world literature. Traditionally splenectomy was the treatment of choice. However, with the recognition of the important immunological function of the spleen, new techniques to preserve splenic function have been developed. This case emphasizes that in selected cases splenic preservation is appropriate.

A Rapid Culture Technique Produces Functional Dendritic-Like Cells from Human Acute Myeloid Leukemia Cell Lines

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Jian Ning

2011-01-01

Full Text Available Most anti-cancer immunotherapeutic strategies involving dendritic cells (DC as vaccines rely upon the adoptive transfer of DC loaded with exogenous tumour-peptides. This study utilized human acute myeloid leukemia (AML cells as progenitors from which functional dendritic-like antigen presenting cells (DLC were generated, that constitutively express tumour antigens for recognition by CD8+ T cells. DLC were generated from AML cell lines KG-1 and MUTZ-3 using rapid culture techniques and appropriate cytokines. DLC were evaluated for their cell-surface phenotype, antigen uptake and ability to stimulate allogeneic responder cell proliferation, and production of IFN-γ; compared with DC derived from normal human PBMC donors. KG-1 and MUTZ-3 DLC increased expression of CD80, CD83, CD86, and HLA-DR, and MUTZ-3 DLC downregulated CD14 and expressed CD1a. Importantly, both KG-1 and MUTZ-3-derived DLC promoted proliferation of allogeneic responder cells more efficiently than unmodified cells; neither cells incorporated FITC-labeled dextran, but both stimulated IFN-γ production from responding allogeneic CD8+ T cells. Control DC produced from PBMC using the FastDC culture also expressed high levels of critical cell surface ligands and demonstrated good APC function. This paper indicates that functional DLC can be cultured from the AML cell lines KG-1 and MUTZ-3, and FastDC culture generates functional KG-1 DLC.

Tolerogenic dendritic cells for regulatory T cell induction in man

Directory of Open Access Journals (Sweden)

Verena eRaker

2015-11-01

Full Text Available Dendritic cells are (DC highly specialized professional antigen-presenting cells (APC that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively well understood. Phase I trials have been conducted in autoimmune disease, with results that emphasize the feasibility and safety of treatments with tolerogenic DC. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of transplantation medicine and allergic and autoimmune diseases is strong. This review will give an overview on efforts and protocols to generate human tolerogenic DC with focus on IL-10-modulated DC as inducers of regulatory T cells and discuss their clinical applications and challenges faced in further developing this form of immunotherapy.

Poly-I:C Decreases Dendritic Cell Viability Independent of PKR Activation

DEFF Research Database (Denmark)

Larsen, Hjalte List; Pedersen, Anders Elm

2012-01-01

Vaccination with tumor-antigen pulsed, monocyte-derived dendritic cells (DCs) has emerged as a promising strategy in cancer immunotherapy. The standard DC maturation cocktail consists of a combination of tumor necrosis factor-α (TNF-α)/interleukin (IL)-1β/IL-6 and prostaglandin E2 (PGE2...

Investigating evolutionary conservation of dendritic cell subset identity and functions

Directory of Open Access Journals (Sweden)

Thien-Phong eVu Manh

2015-06-01

Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

Case report on the role of radiofrequency-assisted spleen-preserving surgery for splenic metastasis in the era of check-point inhibitors.

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Mudan, Satvinder; Kumar, Jayant; Mafalda, Neves C; Kusano, Tomokazu; Reccia, Isabella; Zanallato, Artur; Dalgleish, Angus; Habib, Nagy

2017-12-01

An isolated splenic metastasis is a rare phenomenon noted in advanced stage melanoma. We report the role of radiofrequency (RF) -based splenic-preserving splenectomy in a patient with a solitary splenic metastasis from advanced stage melanoma that was managed with checkpoint inhibitors. We report a case of a 60-year-old man who presented with multiple lung metastases and a solitary splenic metastasis with advanced stage melanoma following excision of primary from his trunk 2.3 years back. Considering the diagnosis of advanced stage melanoma with multiple lung metastases and a solitary splenic metastasis, and its ongoing progressive nature. This case was discussed in the tumour board meeting. A decision was made to commence treatment with immunotherapy in the form of PD-1 inhibitor (programmed cell death 1 receptor) pembrolizumab. Follow-up restaging computer tomography (CT) scan of the abdomen and chest showed a significant reduction in the lung and chest wall lesions, but the splenic lesion remained unchanged. Given the lack of response to treatment in the splenic metastasis and the significant decrease in lung metastases, the multidisciplinary team decided that a partial splenectomy combined with continued immunotherapy treatment would be appropriate as the success of immunotherapy was imminent within the splenic preservation. The postoperative recovery was smooth and the patient was discharged from hospital on the sixth postoperative day with normal platelets and white blood cells. The histopathological analysis of the resected specimen showed a metastatic melanoma with negative margins.At 10-month follow-up after the splenic resection the patient had not experienced further tumour recurrences. Spleen-preserving resection for an isolated, solitary splenic metastasis of melanoma is a feasible approach as it not only preserves the ongoing efficacy of checkpoint inhibitors by preserving the physiological T cell milieu, but the immunomodulation properties of RF can

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs.

Science.gov (United States)

Grimes, Janet A; Prasad, Nripesh; Levy, Shawn; Cattley, Russell; Lindley, Stephanie; Boothe, Harry W; Henderson, Ralph A; Smith, Bruce F

2016-12-03

Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal. Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma. Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

Unsaturated compounds induce up-regulation of CD86 on dendritic cells in the in vitro sensitization assay LCSA.

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Frohwein, Thomas Armin; Sonnenburg, Anna; Zuberbier, Torsten; Stahlmann, Ralf; Schreiner, Maximilian

2016-04-01

Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, and arachidonic acid) in the loose-fit coculture-based sensitization assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a confounder for sensitization testing in vitro. Eight out of 10 tested substances caused significant up-regulation of CD86 on dendritic cells cocultured with keratinocytes and would have been classified as sensitizers; only succinic acid was tested negative, and squalene had to be excluded from data analysis due to poor solubility in cell culture medium. Based on human data, only undecylenic acid can be considered a true sensitizer. The true sensitizing potential of 1-octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known as sensitizers, but their esters are contact allergens. A group of 18- to 20-carbon chain unsaturated fatty acids (linoleic acid, oleic acid, alpha-linolenic acid, and arachidonic acid) elicited the strongest reaction in vitro. This is possibly due to the formation of pro-inflammatory lipid mediators in the cell culture causing nonspecific activation of dendritic cells. In conclusion, both the LLNA and the LCSA seem to provide false-positive results for unsaturated fatty acids. The inclusion of T cells in dendritic cell-based in vitro sensitization assays may help to eliminate false-positive results due to nonspecific dendritic cell activation. This would lead to more accurate prediction of sensitizers, which is paramount for consumer health protection and occupational safety.

Management of splenic trauma--changing concepts.

Science.gov (United States)

Reihneŕ, E; Brismar, B

1995-03-01

During the last two decades the reported risk of overwhelming postsplenectomy infection (OPSI) has resulted in a conservative approach to splenic trauma, with the aim of splenic salvage. The appropriateness of this strategy is now questioned. The risk of OPSI varies with age and indication for splenectomy from less than 1% in adults to more than 4% in children. Pneumococcus is the causative agent in about 60% of cases. A prerequisite for splenic preservation procedures should be a haemodynamically stable patient without other intraabdominal injuries. The benefits derived from non-operative treatment of splenic salvage procedures may be overshadowed by the potential risk of transfusion-related bacterial and viral diseases. Polyvalent pneumococcal vaccines given early after splenectomy appear to reduce the incidence of OPSI substantially.

Dendritic cells sensitize TCRs through self-MHC-mediated Src family kinase activation

Czech Academy of Sciences Publication Activity Database

Meraner, P.; Hořejší, Václav; Wolpl, A.; Fischer, G.F.; Stingl, G.; Maurer, D.

2007-01-01

Roč. 178, č. 4 (2007), s. 2262-2271 ISSN 0022-1767 Institutional research plan: CEZ:AV0Z50520514 Keywords : TCR * dendritic cells * Src kinases Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.068, year: 2007

Prospective clinical testing of regulatory dendritic cells (DCreg) in organ transplantation

OpenAIRE

ANGUS W THOMSON; ALAN F ZAHORCHAK; Mohamed B. Ezzelarab; Lisa H. Butterfield; Fadi G. Lakkis; Diana M Metes

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

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Naymagon, Leonard; Pendurti, Gopichand; Billett, Henny H

2015-01-01

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Astragalus root and elderberry fruit extracts enhance the IFN-β stimulatory effects of Lactobacillus acidophilus in murine-derived dendritic cells.

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Hanne Frøkiær

Full Text Available Many foods and food components boost the immune system, but little data are available regarding the mechanisms by which they do. Bacterial strains have disparate effects in stimulating the immune system. In dendritic cells, the gram-negative bacteria Escherichia coli upregulates proinflammatory cytokines, whereas gram-positive Lactobacillus acidophilus induces a robust interferon (IFN-β response. The immune-modulating effects of astragalus root and elderberry fruit extracts were examined in bone marrow-derived murine dendritic cells that were stimulated with L. acidophilus or E. coli. IFN-β and other cytokines were measured by ELISA and RT-PCR. Endocytosis of fluorescence-labeled dextran and L. acidophilus in the presence of elderberry fruit or astragalus root extract was evaluated in dendritic cells. Our results show that both extracts enhanced L. acidophilus-induced IFN-β production and slightly decreased the proinflammatory response to E. coli. The enhanced IFN-β production was associated with upregulation of toll-like receptor 3 and to a varying degree, the cytokines IL-12, IL-6, IL-1β and TNF-α. Both extracts increased endocytosis in immature dendritic cells, and only slightly influenced the viability of the cells. In conclusion, astragalus root and elderberry fruit extracts increase the IFN-β inducing activity of L. acidophilus in dendritic cells, suggesting that they may exert antiviral and immune-enhancing activity.

[Electroacupuncture Intervention Enhances Splenic Natural Killer Cell Activity via Inhibiting Phosphorylation of ERK 5 in the Hypothalamus of Surgically Traumatized Rats].

Science.gov (United States)

Chen, Yan; Li, Jing; Zhu, Ke-ying; Xiao, Sheng; Wang, Yan-qing; Wu, Gen-cheng; Wang, Jun

2015-06-01

To observe the effect of electroacupuncture (EA) on cytotoxic activity of splenic natural killer (NK) cells after surgical trauma via extracellular signal-regulated kinase (ERK) 5 pathway in the rats' hypothalamus, so as to explore its mechanism underlying improving immune disorders after surgery. Sprague-Dawley rats were randomly divided into the following 6 groups: control, trauma model, EA, sham EA, 4 nmol-BIX 02188 (an inhibitor for ERK 5 catalytic activity) and 20 nmol-BIX 02188 (n = 6 rats per group). The surgical trauma model was established by making a longitudinal incision (6 cm in length) along the median line of the back to expose the spinal column and another longitudinal incision along the abdominal median line. EA (2 Hz/15 Hz, 1 - 2 mA) was applied to bilateral "Zusanli" (ST 36) for 30 min immediately after surgery. For rats of the BIX groups, intra-lateral ventricular microinjection of BIX 02188 (10 µL, 4 nmol or 20 nmol, or saline for control rats) was conducted 30 min before the surgery. The expression level and protein of phosphorylated ERK 5 (p-ERK 5) and corticotropin-releasing factor (CRF) protein were measured by immunohistochemistry and Western blot, respectively. The cytotoxicity of splenic NK cells and the expression of splenic Perforin and Granzyme-B genes were measured by lactate dehydrogenase (LDH) release assay and real-time PCR, respectively. In comparison with the control group, hypothalamic p-ERK 5 immunoactivity, p-ERK 5 protein and CRF protein expression levels were significantly up-regulated in the model group (Psplenic NK cell cytotoxicity and Perforin mRNA and Granzyme-B mRNA expression levels were notably down-regulated in the model group (P 0. 05) except the increased p-ERK 5 protein in the 4 nmol-BIX 02188 group. In addition, the down-regulated NK cell activity, Perforin mRNA and Granzyme-B mRNA expression levels were significantly reversed in the EA and 20 nmol-BIX 02188 groups (Psplenic NK cytotoxicity and Perforin and

Macrophages support splenic erythropoiesis in 4T1 tumor-bearing mice.

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Min Liu

Full Text Available Anemia is a common complication of cancer; a role of spleen in tumor-stress erythropoiesis has been suggested. However, the molecular mechanisms involved in the splenic erythropoiesis following tumor maintenance remain poorly understood. Here we show that tumor development blocks medullar erythropoiesis by granulocyte colony-stimulating factor (G-CSF and then causes anemia in murine 4T1 breast tumor-bearing mice. Meanwhile, tumor-stress promotes splenic erythropoiesis. Splenectomy worsened tumor-induced anemia, and reduced tumor volume and tumor weight, indicating the essential role of spleen in tumor-stress erythropoiesis and tumor growth. Tumor progression of these mice led to increased amounts of bone morphogenetic protein 4 (BMP4 in spleen. The in vivo role of macrophages in splenic erythropoiesis under tumor-stress conditions was investigated. Macrophage depletion by injecting liposomal clodronate decreased the expression of BMP4, inhibited splenic erythropoiesis, aggravated the tumor-induced anemia and suppressed tumor growth. Our results provide insight that macrophages and BMP4 are positive regulators of splenic erythropoiesis in tumor pathological situations. These findings reveal that during the tumor-stress period, the microenvironment of the spleen is undergoing changes, which contributes to adopt a stress erythropoietic fate and supports the expansion and differentiation of stress erythroid progenitors, thereby replenishing red blood cells and promoting tumor growth.

Juvenile colon cancer at the splenic flexure with a splenic abscess developing 22 years after irradiation for a neuroblastoma

International Nuclear Information System (INIS)

Tamura, Toshihisa; Higure, Aiichiro; Akiyama, Masaki; Nagata, Naoki; Hirata, Keiji; Yamaguchi, Koji

2010-01-01

A 23-year-old woman who had an operation and chemo-radiation therapy for a neuroblastoma of the left adrenal gland at the age of five months developed a fever and left hypochondralgia when she was 22 years old. A splenic abscess was noted. Percutaneous drainage was done, but the splenic abscess recurred. There was no recurrence of the neuroblastoma. Conservative therapy was unsuccessful and a laparotomy was performed. Operative findings included a bulky mass at the splenic flexure which involved the spleen, pancreas tail, and jejunum. Colectomy at the splenic flexure was performed with coresection of the spleen, pancreas tail, and jejunum. The surgical specimen showed mucinous carcinoma of the splenic flexure which invaded the spleen. This case was considered to be an radiation-induced secondary colon cancer. (author)

Another Armament in Gut Immunity: Lymphotoxin-Mediated Crosstalk between Innate Lymphoid and Dendritic Cells

NARCIS (Netherlands)

Spits, H.

2011-01-01

Innate lymphoid cells (ILCs) are novel players in innate immunity. Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria

Splenic Infarction: An Under-recognized Complication of Infectious Mononucleosis?

Science.gov (United States)

Li, Yan; George, Ann; Arnaout, Sami; Wang, Jennifer P; Abraham, George M

2018-03-01

Splenic infarction is a rare complication of infectious mononucleosis. We describe 3 cases of splenic infarction attributed to infectious mononucleosis that we encountered within a 2-month period. We underscore the awareness of this potential complication of infectious mononucleosis and discuss the differential diagnosis of splenic infarction, including infectious etiologies. While symptomatic management is usually sufficient for infectious mononucleosis-associated splenic infarction, close monitoring for other complications, including splenic rupture, is mandated.

REMOD: a tool for analyzing and remodeling the dendritic architecture of neural cells

Directory of Open Access Journals (Sweden)

Panagiotis eBozelos

2016-01-01

Full Text Available Dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations under various physiological or neuropathological conditions. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between the two remains largely elusive. The lack of a systematic approach for remodeling neural cells and their dendritic trees is a key limitation that contributes to this problem. Such causal relationships can be inferred via the use of large-scale neuronal models whereby the anatomical plasticity of neurons is accounted for, in order to enhance their biological relevance and hence their predictive performance. To facilitate this effort, we developed a computational tool named REMOD that allows the structural remodeling of any type of virtual neuron. REMOD is written in Python and can be accessed through a dedicated web interface that guides the user through various options to manipulate selected neuronal morphologies. REMOD can also be used to extract meaningful morphology statistics for one or multiple reconstructions, including features such as sholl analysis, total dendritic length and area, path length to the soma, centrifugal branch order, diameter tapering and more. As such, the tool can be used both for the analysis and/or the remodeling of neuronal morphologies of any type.

Novel dendritic cell-based vaccination in late stage melanoma.

Science.gov (United States)

Schneble, Erika J; Yu, Xianzhong; Wagner, T E; Peoples, George E

2014-01-01

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play an important role in stimulating an immune response of both CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs). As such, DCs have been studied extensively in cancer immunotherapy for their capability to induce a specific anti-tumor response when loaded with tumor antigens. However, when the most relevant antigens of a tumor remain to be identified, alternative approaches are required. Formation of a dentritoma, a fused DC and tumor cells hybrid, is one strategy. Although initial studies of these hybrid cells are promising, several limitations interfere with its clinical and commercial application. Here we present early experience in clinical trials and an alternative approach to manufacturing this DC/tumor cell hybrid for use in the treatment of late stage and metastatic melanoma.

Computed tomographic diagnosis of the splenic trauma

International Nuclear Information System (INIS)

Suzuki, Masayuki; Takashima, Tsutomu; Funaki, Hiromi; Uogishi, Makoto; Isobe, Tsugimasa; Kanno, Shoichi; Ushitani, Kenji; Fuchuh, Kosei; Sakita, Tsuyoshi.

1985-01-01

Three cases (3-year-old, 51-year-old and 17-year-old males) in which splenic trauma was diagnosed by plain computed tomography (CT) are presented. CT images revealed retention of fluid in the abdominal cavity in all cases and clear splenic hematoma and laceration in one case. CT is superior in the visualization of splenic hematoma and hemorrhage in the abdominal cavity accompanied by splenic trauma. It should, however, be noted that the presence of laceration is frequently difficult to detect due to artifacts. Indication for surgery should be decided by evaluating the severity of clinical symptoms. (Namekawa, K.)

Computed tomographic diagnosis of the splenic trauma

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Masayuki; Takashima, Tsutomu; Funaki, Hiromi; Uogishi, Makoto; Isobe, Tsugimasa; Kanno, Shoichi; Ushitani, Kenji; Fuchuh, Kosei; Sakita, Tsuyoshi

1985-01-01

Three cases (3-year-old, 51-year-old and 17-year-old males) in which splenic trauma was diagnosed by plain computed tomography (CT) are presented. CT images revealed retention of fluid in the abdominal cavity in all cases and clear splenic hematoma and laceration in one case. CT is superior in the visualization of splenic hematoma and hemorrhage in the abdominal cavity accompanied by splenic trauma. It should, however, be noted that the presence of laceration is frequently difficult to detect due to artifacts. Indication for surgery should be decided by evaluating the severity of clinical symptoms. (Namekawa, K.).

Scintigraphic evaluation of traumatic splenic lesions in children

International Nuclear Information System (INIS)

Erasmie, U.; Mortensson, W.; Persson, U.; Laennergren, K.; St. Goerans Children's Hospital, Stockholm

1988-01-01

Ninety-eight children with recent blunt abdominal trauma which initially evoked clinical suspicion of splenic injury were examined with colloid scintigraphy of the spleen and the liver using multiple imaging views and with abdominal survey. Nineteen children were, in addition, examined with tomographic scintigraphy. The clinical findings and the course of the disorder were reanalysed. Scintigraphy indicated splenic injury in 56 children and hepatic injury in another 5 children. The left lateral and the left oblique were the optimum imaging views for detecting splenic ruptures. Tomographic scintigraphy did not improve the diagnostic yield. Abdominal survey failed to indicate almost every second case of splenic rupture and provided no additional information of significance. The clinical review agreed with the scintigraphic diagnosis of splenic lesions but, in addition, it suggested possible splenic lesions in another 10 children with normal scintigraphy. This discrepancy cannot be explained as surgery was not employed; the occurrence of splenic lesions too small to become detectable at scintigraphy or to provoke clinically evident symptoms may be supposed. (orig.)

Splenectomy for solitary splenic metastasis of ovarian cancer

International Nuclear Information System (INIS)

Koh, Yang Seok; Kim, Jung Chul; Cho, Chol Kyoon

2004-01-01

Splenic metastases occur in rare cases with a few case reports of patients in the literature. Generally, splenic metastases mean late dissemination of a disease. Solitary splenic metastases from solid tumors are extremely unusual. We report a case of a patient with ovarian mucinous cystadenocarcinoma who underwent splenectomy for isolated parenchymal metastasis. Ovarian epithelial tumors comprised most of isolated splenic metastases from gynecologic tumor. When isolated splenic recurrence is suspected on image studies and serum tumor markers, intraabdominal gross findings should be examined to exclude peritoneal carcinomatosis. If only spleen was under suspicion of recurrence of ovarian cancer, splenectomy may play a therapeutic role

Scintigraphic follow up of autologous splenic grafts: An experimental and clinical study

International Nuclear Information System (INIS)

Reilmann, H.; Creutzig, H.; Pabst, R.; Kamran, D.

1984-01-01

The risk of overwhelming sepsis in splenectomized patients is well known and autotransplantation of splenic tissue might be considered as a prophylactic approach. Little is known, however, of the success of grafting in man. In six patients with autologous grafts after emergency splenectomy the ''trapping function'' (TF) was measured by sequential scintigraphy with heat damaged red cells every third month. To correlate TF with blood flow and histology, different experiments were done in pigs: ligation of the splenic artery or partial splenectomy or total splenectomy with grafting of fragments either subfascially or in the greater momentum. TF, blood flow with Rb-86 and immune response was measured at different times after surgery. Remnants left at the main vessels did not grow, while splenic tissue left at smaller vessels increased in size. There were great differences in blood flow per gram splenic tissue, but a significant correlation between TF and blood flow. All experimental grafts showed a normal function both of the white and the red pulp. In patients there was a growth of grafts in four, while in two no TF could be measured. TF is an indicator of relative blood flow to splenic grafts and therefore useful in the follow up of grafted patients

Splenic injury diagnosis & splenic salvage after trauma

NARCIS (Netherlands)

Olthof, D.C.

2014-01-01

Non-operative management (NOM) has replaced surgery as the treatment of choice for hemodynamically stable patients with splenic injury after trauma. The growing use of NOM for blunt abdominal organ injury has been made possible by the progress in the quality and availability of the multidetector CT

Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

International Nuclear Information System (INIS)

Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M.; Shearkhani, Omid

2017-01-01

MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

Incidental splenic nodules found on MR imaging done for assessment of iron overload in children

Energy Technology Data Exchange (ETDEWEB)

Ahyad, Rayan A.; Lam, Christopher Z.; Navarro, Oscar M. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Shearkhani, Omid [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

2017-06-15

MR imaging is used to assess iron overload in patients with hemoglobinopathies and in those who have undergone multiple blood transfusions. Sometimes splenic nodules are found incidentally on these examinations and this may cause diagnostic uncertainty. To determine the prevalence, imaging characteristics and evolution of splenic nodules found on MR imaging for iron overload evaluation. Retrospective review of all MR imaging examinations performed for iron overload assessment from 2005 to 2015 in a tertiary pediatric hospital. The presence of focal splenic nodules including number, size, signal characteristics and changes on follow-up MR imaging were recorded. Relevant patient clinical information including underlying hematological disease was also documented. A total of 318 patients had MR imaging for iron overload assessment. Of these, 25 (8%) had at least one incidental splenic nodule. Sickle cell disease was present in 22 patients (88%) and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the nodules had high signal intensity compared to the remainder of the spleen in 23 patients (92%) and low signal intensity in the remaining 2 (8%). In all patients (100%) the nodules showed progressive loss of signal intensity with increasing echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which showed an increase in the size of the splenic nodules in 7 patients (35%) stability in 11 (55%) and a decrease in size in 2 (10%). It is not uncommon to find splenic nodules during MR evaluation of iron overload. In patients with sickle cell disease, most of these nodules are thought to represent preserved splenic tissue and appear hyperintense compared to the remainder of the spleen. They frequently remain stable on follow-up imaging, although about a third of them may show growth. Awareness of these nodules is important to avoid concern for potential malignancy and unnecessary investigations. (orig.)

Molecular detection of vector-borne pathogens in blood and splenic samples from dogs with splenic disease.

Science.gov (United States)

Movilla, Rebeca; Altet, Laura; Serrano, Lorena; Tabar, María-Dolores; Roura, Xavier

2017-03-13

The spleen is a highly perfused organ involved in the immunological control and elimination of vector-borne pathogens (VBP), which could have a fundamental role in the pathogenesis of splenic disease. This study aimed to evaluate certain VBP in samples from dogs with splenic lesions. Seventy-seven EDTA-blood and 64 splenic tissue samples were collected from 78 dogs with splenic disease in a Mediterranean area. Babesia spp., Bartonella spp., Ehrlichia/Anaplasma spp., Hepatozoon canis, Leishmania infantum, hemotropic Mycoplasma spp. and Rickettsia spp. were targeted using PCR assays. Sixty EDTA-blood samples from dogs without evidence of splenic lesions were included as a control group. More than half (51.56%) of the biopsies (33/64) were consistent with benign lesions and 48.43% (31/64) with malignancy, mostly hemangiosarcoma (25/31). PCR yielded positive results in 13 dogs with spleen alterations (16.67%), for Babesia canis (n = 3), Babesia gibsoni (n = 2), hemotropic Mycoplasma spp. (n = 2), Rickettsia massiliae (n = 1) and "Babesia vulpes" (n = 1), in blood; and for B. canis, B. gibsoni, Ehrlichia canis and L. infantum (n = 1 each), in spleen. Two control dogs (3.3%) were positive for B. gibsoni and H. canis (n = 1 each). Benign lesions were detected in the 61.54% of infected dogs (8/13); the remaining 38.46% were diagnosed with malignancies (5/13). Infection was significantly associated to the presence of splenic disease (P = 0.013). There was no difference in the prevalence of infection between dogs with benign and malignant splenic lesions (P = 0.69); however B. canis was more prevalent in dogs with hemangiosarcoma (P = 0.006). VBP infection could be involved in the pathogenesis of splenic disease. The immunological role of the spleen could predispose to alterations of this organ in infected dogs. Interestingly, all dogs with B. canis infection were diagnosed with hemangiosarcoma in the present survey. As previously

Non-operative management for penetrating splenic trauma : how far can we go to save splenic function?

NARCIS (Netherlands)

Spijkerman, Roy; Teuben, Michel Paul Johan; Hoosain, Fatima; Taylor, Liezel Phyllis; Hardcastle, Timothy Craig; Blokhuis, Taco Johan; Warren, Brian Leigh; Leenen, Luke Petrus Hendrikus

2017-01-01

BACKGROUND: Selective non-operative management (NOM) for the treatment of blunt splenic trauma is safe. Currently, the feasibility of selective NOM for penetrating splenic injury (PSI) is unclear. Unfortunately, little is known about the success rate of spleen-preserving surgical procedures. The aim

Transcatheter Splenic Artery Occlusion for Treatment of Splenic Artery Steal Syndrome After Orthotopic Liver Transplantation