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Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma.

PURPOSE: Six American Joint Committee on Cancer stage IV melanoma patients were enrolled into a Phase I study of vaccination with autologous CD34(+)-derived dendritic cells transduced with a modified vaccinia Ankara virus encoding human tyrosinase gene (MVA-hTyr). EXPERIMENTAL DESIGN: Patients received a first intravenous injection of 1 x 10(8) MVA-hTyr-transduced dendritic cells, followed by three s.c. injections at a 14-day interval. RESULTS: Treatment was well tolerated, except for low-grade fever (three of six patients), mild erythema at injection site (five of six), and vitiligo (two of

Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo.

Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the suppressor activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+) DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25(+) Treg cells di

Unique monoclonal antibodies define expression of Fc gamma RI on macrophages and mast cell lines and demonstrate heterogeneity among subcutaneous and other dendritic cells.

The mouse Fc gamma RI is one of the most fundamentally important FcRs. It participates in different stages of immunity, being a low affinity receptor for T-independent IgG3 and yet a high affinity receptor for IgG2a, the product of a Th1 immune response. However, analysis of this receptor has been difficult due largely to the failure to generate specific Abs to this FcR. We have made use of the polymorphic differences between BALB/c and NOD/Lt mice to generate mAb specific for the Fc gamma RI of BALB/c and the majority of in-bred mouse strains. Three different mAb were obtained that detected F

Effects of tumor necrosis factor alpha on dendritic cell accumulation in lymph nodes draining the immunization site and the impact on the anticryptococcal cell-mediated immune response.

Cell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-alpha) have been shown to be essential in acquired protection against Cryptococcus neoformans. Induction of a protective anticryptococcal CMI response includes increases in dendritic cells (DC) and activated CD4(+) T cells in draining lymph nodes (DLN). During the expression phase, activated CD4(+) T cells accumulate at a peripheral site where cryptococcal antigen is injected, resulting in a classical delayed-type hypersensitivity (DTH) reaction. Induction of a nonprotective anticryptococcal CMI response results in no si

Additive inhibition of dendritic cell allostimulatory capacity by alcohol and hepatitis C is not restored by DC maturation and involves abnormal IL-10 and IL-2 induction.

BACKGROUND: Excessive alcohol use results in impaired immunity, and it is associated with increased incidence and progression of chronic hepatitis C virus (HCV) infection. Here we investigated the effects of HCV infection and alcohol on myeloid dendritic cells (DC) that are critical in antiviral immunity. METHODS: Immature and mature DCs were generated from monocytes of chronic HCV infected patients (HCV-DC) and controls (N-DC) with IL-4 plus granulocyte-macrophage colony stimulating factor (GM-CSF) in the presence or absence of alcohol (25 mM). DC allostimulatory capacity was tested in mixed

Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens.

Upon loading with microbial Ag and adoptive transfer, dendritic cells (DC) are able to induce immunity to infections. This offers encouragement for the development of DC-based vaccination strategies. However, the mechanisms underlying the adjuvant effect of DC are not fully understood, and there is a need to identify Ag with which to arm DC. In the present study, we analyzed the role of DC-derived IL-12 in the induction of resistance to Leishmania major, and we evaluated the protective efficacy of DC loaded with individual Leishmania Ag. Using Ag-pulsed Langerhans cells (LC) from IL-12-deficie

Establishment and characterization of transplantable tumor line (KB) and cell lines (KB-P and KB-D8) from a rat thymus-derived dendritic cell sarcoma.

A transplantable tumor line (KB) was established in syngeneic rats from a naturally occurring sarcoma that had arisen in the thymus of a 24-month-old male F344 rat. Further, a cell line (KB-P) was induced from KB and a cloned cell line (KB-D8) was isolated from KB-P. The primary thymic tumor and KB tumors showed heterogeneous histological growth patterns such as sheet-like, ill-defined bundle, fascicular and interwoven fashions, consisting of spindle cells, oval cells and histiocytic large round cells. Immunohistochemically, neoplastic cells in KB tumors and KB-P and KB-D8 cultures reacted to

Generation of dendritic cells ex vivo: differences in steady state versus mobilized blood from patients with breast cancer, with lymphoma, and from normal donors.

Dendritic cells (DC) are potent antigen-presenting cells that are integral to the initiation of T cell immunity. The ability to culture these cells in vitro has allowed DC immunotherapy to be investigated as a mechanism of enhancing immune responses against various malignancies. We examined the optimal time for generating DC and compared DC generated from normal donors for allogeneic blood stem cell transplantation, or patient's with non-Hodgkin's lymphoma or breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. Experiments were conducted to compare DC cultu

Intratracheal priming with ovalbumin- and ovalbumin 323-339 peptide-pulsed dendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation.

Dendritic cells (DC) are the primary APC responsible for the capture of allergens in the airways and the shuttling of processed allergens to the draining lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly understood. In addition, the feasibility of asthma induction by DC priming has not been directly tested. In this report an asthma model using intratracheally (i.t.) injected splenic DC was used to address these issues. DC pulsed with a model Ag OVA or the major MHC class II-restricted OVA T epitope peptide

CD34(+) cord blood cells expressing cutaneous lymphocyte-associated antigen are enriched in granulocyte-macrophage progenitors and support extensive amplification of dendritic cell progenitors.

OBJECTIVE: We evaluated the frequency of hematopoietic progenitor cells (HPC) in CD34(+)CLA(+) (cutaneous lymphocyte-associated antigen) and CD34(+)CLA(-) cord blood cells, and followed cellular growth and HPC production during cultures in Flt3 ligand, thrombopoietin, and stem cell factor (FTS). MATERIALS AND METHODS: Immunomagnetic bead-purified CD34(+) cells were sorted into CD34(+)CLA(+) or CD34(+)CLA(-) cells. HPC frequency was assessed by clonal assays in methylcellulose either ex vivo or after, 7, 14, or 21 days of culture with FTS. Dendritic cell (DC) progenitors were evaluated after i

Dendritic cells induce CD4+ and CD8+ T-cell responses to Mycobacterium bovis and M. avium antigens in Bacille Calmette Guérin vaccinated and nonvaccinated cattle.

Few data are available regarding the induction of memory T-lymphocyte responses in cattle following Bacille Calmette Guérin (BCG) vaccination. Studies of the immune response induced by BCG vaccination provide an insight into the basis of antimycobacterial immunity that could be exploited for the development of more effective vaccination strategies. We used autologous dendritic cells (DC) infected with Mycobacterium bovis Bacille Calmette Guérin (BCG) or pulsed with purified protein derivative from M. bovis (PPD-B) or M. avium (PPD-A) to assess responses of CD4+, CD8+ and WC1+ gammadelta TCR+ l

Differences in interleukin-12 and -15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice.

The mechanisms responsible for the resistance of C57BL/6 mice and for the susceptibility of BALB/c mice to infection with Listeria monocytogenes were studied by comparing early IL-12 and IL-15 production by dendritic cells (DC) after infection with L. monocytogenes. Splenic DC expressing CD11b(low) and CD11c(+) obtained from C57BL/6 mice at 3 and 6 h after L. monocytogenes infection expressed higher levels of IL-12 p40 mRNA and IL-12 p40 protein than did those from BALB/c mice. Concurrently, a larger amount of IFN-gamma was produced by the splenic T cells from C57BL/6 mice in response to immob

Differential effects of CD40 ligand/trimer stimulation on the ability of dendritic cells to replicate and transmit HIV infection: evidence for CC-chemokine-dependent and -independent mechanisms.

The role of exogenous stimulation of CD40 by CD40 ligand (CD40L) in dendritic cell (DC) maturation, CC-chemokine production, and CCR5 receptor expression was examined using a soluble trimeric CD40L agonist protein (CD40LT). Stimulation of monocyte-derived DCs with CD40LT enhanced the production of the CC-chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES and diminished surface expression of CCR5. Based on these findings, the functional role of CD40LT stimulation on the ability of DCs to replicate and transmit HIV viral infection was studied. The addition of CD40LT

The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia.

Antibodies to an excitatory amino acid transporter (EAAT4) label a glycoprotein of approximately 65 kDa strongly in the cerebellum and weakl … nes expressing high levels of zebrin II (aldolase C). The labeling of Purkinje cell spines and thin dendrites is stronger than that of large diameter dendrites and cell bodies. EAAT4 is present at low concentrations in the synaptic membrane, but is highly enriched in the parts of the dendritic and spine membranes facing astrocytes (which express GLAST and G …

Increased nitric oxide (NO) production by antigen-presenting dendritic cells is responsible for low allogeneic mixed leucocyte reaction (MLR) in primary biliary cirrhosis (PBC).

The levels of blastogenesis in allogeneic MLR containing T cells from one normal volunteer and irradiated dendritic cells from 29 patients with PBC, 17 patients with chronic hepatitis type C (CH-C) and 22 allogeneic normal controls were compared to see if there is any role of antigen-presenting cells (APC) in the pathogenesis of PBC. The stimulatory capacity of dendritic cells from PBC was significantly lower compared with that of dendritic cells from CH-C (P < 0.05) and normal controls (P < 0.05), which could not be attributable either to the levels of expression of surface molecules, such as

Different in situ distribution patterns of dendritic cells having Langerhans (T6+) and interdigitating (RFD1+) cell immunophenotype in psoriasis, atopic dermatitis, and other inflammatory dermatoses.

Dendritic cells bearing Langerhans cell (OKT6+) or interdigitating cell (RFD1+) immunophenotype may be regularly detected within the dermis of chronic skin diseases characterized by a lymphohistiocytic (lymphoreticular) infiltrate. These 2 subsets of antigen-presenting cells within the dermis of lesions of exacerbating chronic plaque psoriasis, exacerbating nummular dermatitis (discoid eczema), atopic dermatitis, allergic contact dermatitis, pityriasis rosea, lichen ruber planus, and cutaneous lupus erythematosus were quantified using computer-assisted morphometry. The mean dendrite length per

Population morphology implies a common developmental blueprint for Drosophila motion detectors.

T4 and T5 neurons are the first direction-selective neurons in the visual pathway. They are the most numerous cell types in the fly brain (~6000 within each optic lobe) and, as a population, their compact dendritic arbours span the entire visual field. They are classified into four subtypes (a, b, c, and d). Each subtype encodes one of four orthogonal motion directions (up, down, forwards, backwards). Crucially, the dendrites of these neurons are oriented inversely to the functional direction of motion which they encode. This dendritic orientation is what ultimately determines their functional…

Нейрональный LRP4 регулирует синапсовое образование в развивающихся CNS.

Белок 4 (LRP4), связанный с низкоплотностью липопротеинового рецептора, имеет важное значение для создания нейромускульного соединения мышечных волокон. Здесь мы показываем, что LRP4 также выражается эмбрионами кортикальных и гиппокампальных нейронов и что снижение регулирования LRP4 в этих нейронах приводит к снижению плотности синапсов и количества первичных дендритов. Таким образом, перевыражение LRP4 в культивированных нейронах имело обратный эффект, вызывая более, но более короткие первичные дендриты с увеличением числа позвоночников. Транссинаптическое отслеживание при помощи вируса беше

Совпадение в аннотации оригинала
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Ac…

[Glucocorticoid and Bone. Osteocytic osteolysis : potential modulation by glucocorticoids].

Glucocorticoid-induced osteoporosis is mediated primarily by activity of glucocorticoid receptors expressed in osteoblasts, osteocytes and osteoclasts. Bone matrix harbors numerous osteocyte lacunae containing osteocytes. Each osteocyte extends numerous dendrites into canaliculi where dendrite tips make contact with dendrites of nearby neighboring osteocytes and form gap junctions between osteocytes. Osteocytes near the bone surface also contact osteoblasts and osteoclasts through dendrites, thereby establishing communication within an entire bone. Curiously, osteocytes themselves have been sh…

[Prionic neuroinvasion and cerebellar lesion in Creutzfeldt-Jakob disease].

Examining the histological brain sections of patients with Creutzfeldt-Jakob disease (CJD) showed the accumulation of PrP(CJD) in the cerebellar cortical layers. In nCJD, the prion accumulated mainly in the granular layer in the area of synapses of moss fibers with granular cell dendrites in the cerebellar glomeruli and in the molecular layer in the area of the synapses formed by granular cell axons and great stellate neurons of the granular layer with the dendrites of Purkinje's piriform cells of busket cells and Golgi's cells. PrP(CJD) amyloid plaques were formed in these regions. In sporadi…