Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40+ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC also showed weak nonspecific esterase staining and had the ability to induce an allogeneic mixed lymphocyte reaction. In this study, we further show that in the presence of surrogate activated T cells in the form of CD40 ligation and IL-2, IDC enhance the proliferation of naive B cells and induce their differentiation into plasma cells producing IgM. Evidence for the anatomical co-localization of naive B cells and IDC in the T cell area together with the data obtained in vitro implies a role for IDC in the initiation of the extrafollicular reaction.
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PMID:Human interdigitating dendritic cells directly stimulate CD40-activated naive B cells. 917 20

Using a combination of GM-CSF, SCF, flk-2/flt-3 ligand, and IL-4, dendritic cells (DC) have been generated in vitro from the adherent fraction of mononuclear cells isolated from the blood of patients with MM. Analysis of cell yield showed no significant difference in DC yield (numbers or percentage of leucocytes) or total number of leucocytes generated in myeloma cultures compared to similar cultures prepared using mononuclear cells from the blood of healthy donors. The mean number of DC produced after 10d of culture were 8.19 x 10(5) and 9.87 x 10(5) cells (41% and 51% of all leucocytes) for the myeloma and normal cultures respectively. Flow cytometry investigation of phenotypic markers including CD1a, HLA-DR, CD80 (BB1/B7.1) and CD86 (B70/B7.2), and functional status (stimulatory potential in allogeneic mixed leucocyte reactions (MLR)) confirmed the generation of cells phenotypically identified as cultured DC. In addition, these cells were more effective than PBMC at stimulating allogeneic PBMC proliferation. These data demonstrate no difference between DC generated from patients with MM and healthy donors. This study was considered a prerequisite for future investigations directed towards developing effective immunotherapies for myeloma.
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PMID:Dendritic cells generated from the blood of patients with multiple myeloma are phenotypically and functionally identical to those similarly produced from healthy donors. 932 98

In this study, we analyzed the expression and function of the lymphocyte surface lectin NKRP1A on peripheral blood monocytes (Mo) or Mo and dendritic cells (DC) derived from thymic and bone marrow precursors. De novo expression of NKRP1A and CD14 molecules was detected upon culture of CD2- CD3- CD14- CD16- CD1a- NKRP1A- immature thymic precursors for 7 days in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Under these culture conditions, by day 21, a fraction of cells had lost CD14 and acquired both CD80 (B7.1) and CD86 (B7.2) molecules. These cells displayed a DC-like morphology and were surface NKRP1A positive. CD34+ NKRP1A- CD14- precursors, isolated from bone marrow and cultured in the presence of GM-CSF, also expressed both NKRP1A and CD14: these antigens were newly expressed on about one third of cells which had lost the CD34 precursor marker. In addition, NKRP1A was constitutively present on resting CD14+ peripheral blood Mo. When these cells were cultured in the presence of GM-CSF, the resulting DC population retained the expression of NKRP1A and acquired CD80, while they lost the CD14 antigen. Functional analysis revealed that the engagement of NKRP1A molecule leads to a strong intracellular calcium ([Ca2+]i) increase both in resting peripheral blood Mo and in vitro-derived DC. [Ca2+]i increase was mainly due to extracellular calcium influx, as it was completely abrogated by the addition of EGTA. More importantly, the engagement of the NKRP1A molecule induced interleukin (IL)-1 beta and IL-12 production by resting Mo and DC, respectively. Altogether these data indicate that NKRP1A lectin is present at the surface of Mo and DC and may play a relevant role in the activation and function of both cell types.
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PMID:Expression and function of NKRP1A molecule on human monocytes and dendritic cells. 939 25

FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate), one of the pyridinyl imidazoles, is an immunosuppressive agent which was developed to inhibit proinflammatory cytokine production. We examined the effect of FR167653 on the differentiation and maturation phases of both human bone marrow-derived dendritic cells (BM-DC) and blood monocyte-derived DC (Mo-DC). DC induced from either BM-DC or Mo-DC progenitors in the presence of FR167653 had lower expression of CD1a, CD83 and CD86 (B7.2). FR167653 also significantly suppressed the ability of Mo-DC to produce both TNF-alpha and IL-1beta in response to LPS stimulation. Mixed lymphocyte reaction (MLR) stimulation was significantly lower in FR167653-treated Mo-DC than in control Mo-DC, although the suppressive effect of FR167653 was much less on BM-DC. These results indicate novel immunosuppressive properties of FR167653, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases through down-regulation of DC differentiation and maturation.
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PMID:Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34+ cells to dendritic cells. 1078 47

We present a simple yet powerful method for the isolation and analysis of exosomes released by antigen-presenting cells (APC). Exosomes are small vesicles (40-90 nm) released by APC, and may have an immuno-regulatory function in vivo. Such exosomes originate from MHC class II peptide loading compartments and, as such, express high levels of MHC Class II. We have utilised magnetic beads, coated with monoclonal antibodies specific for HLA DP, DQ, DR for the specific isolation of exosomes from cell-free supernatants. Beads coated with exosomes are subsequently stained with conjugated antibodies, and analysed by flow cytometry. Characterisation of exosomes by this method demonstrated that exosomes derived from B-lymphocytes express abundant MHC Class I and II molecules. Other immunologically important molecules detected included the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86). The adhesion molecule ICAM-1 (CD54) was also detected. These exosomes also expressed the B cell marker CD20, and the complement inhibitory protein CD59. The expression of CD63, a lysosomal marker, was variable, and there was no detectable expression of transferrin receptor (CD71). Monocyte derived dendritic cells (cultured for 7 days in GM-CSF/IL-4), demonstrated an immature phenotype, and secreted exosomes with a similar phenotype, with abundant MHC molecules. The expression of CD63 was consistently strong, and the MHC Class I-like molecule CD1a was also present, suggesting a possible function in the presentation of lipid antigens. Again CD59 was expressed suggesting a possible role for APC exosomes in complement regulation. There was no detectable CD71, CD40, CD14, CD20 or CD83. Modification of the extraction protocol allowed a comparative analysis of exosome secretion under various conditions. Treatment of cells with calcium ionophore, or phorbol ester resulted in apparent increases in exosome release, while the phosphatidyl inositol 3-kinase inhibitor, wortmannin, reduced exosome secretion. The immuno-magnetic isolation and analysis of exosomes is a versatile and rapid tool for the analysis of APC exosomes, and may prove a valuable tool for the study of exosome biology.
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PMID:Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. 1115 May 47

Transduction of dendritic cells (DCs) with genes encoding tumor-associated antigen or with other genes that enhance immune reaction has been theorized to be potentially useful for enhancing the efficiency of DC-based immunotherapy. However, gene transduction of DCs generated from human peripheral blood monocytes has been of limited use because of the low efficiency. Here, we report that the efficiency of in vitro adenovirus-mediated gene transduction into human monocyte-derived DCs can be dramatically enhanced by centrifugation. The best conditions for centrifugal gene transduction were determined to be as follows: 2000 x g at 37 degrees C for 2 hr at a multiplicity of infection (MOI) of 10 or greater. By this centrifugal method, approximately 88 and 70% of DCs were gene transducible at an MOI of 50 and 10, respectively. Functional analysis showed that DCs transduced with human interleukin 12 (IL-12)-expressing adenoviral vector under the optimal conditions of centrifugation stably produced IL-12 protein at high levels (8.1 ng/10(6) cells/48 hr). IL-12 gene-modified DCs (DC/IL-12) displayed a more mature phenotype than nontransduced DCs, as judged by decreased expression of CD1a and increased expression of CD83, B7.1 (CD80), B7.2 (CD86), and MHC class I and II molecules. DC/IL-12 showed a high phagocytic ability similar to nontransduced DCs and were significantly superior to control DCs in the stimulation of autologous and allogeneic T lymphocyte responses. The centrifugal transduction method with adenoviral vector might be useful for efficient generation of gene-modified DCs because it is very simple, highly efficient, reproducible, and not cytopathic. IL-12 gene-modified human DCs may be therapeutically useful as a good adjuvant in DC-based immunotherapy.
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PMID:Enhanced efficiency by centrifugal manipulation of adenovirus-mediated interleukin 12 gene transduction into human monocyte-derived dendritic cells. 1124 26

Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs) identified in various tissues, including the skin (Langerhans cells), lymph nodes (interdigitating and follicular DCs), spleen, and thymus. Properties of DCs include the ability to (1) capture, process, and present foreign antigens; (2) migrate to lymphoid-rich tissue; and (3) stimulate innate and adaptive antigen-specific immune responses. Until recently, the ability to study DCs has been limited by their absence in most culture systems. It is now known that specific cytokines can be used to expand DCs to numbers sufficient for their in vitro evaluation and for their use in human immunotherapy trials. Human DCs can be derived from hematopoietic progenitors (CD34+-derived DCs) or from adherent peripheral blood monocytes (monocyte-derived DCs). Cultured DCs can be recognized by a typical veiled morphologic appearance and expression of surface markers that include major histocompatibility complex class II, CD86/B7.2, CD80/B7.1, CD83, and CD1a. DCs are susceptible to a variety of gene transfer protocols, which can be used to enhance biological function in vivo. Transduction of DCs with genes for defined tumor antigens results in sustained protein expression and presentation of multiple tumor peptides to host T cells. Alternatively, DCs may be transduced with genes for chemokines or immunostimulatory cytokines. Although the combination of ex vivo DC expansion and gene transfer is relatively new, preliminary studies suggest that injection of genetically modified autologous DCs may be capable of generating anti-tumor immune responses in patients with cancer. Preclinical animal studies showing potent antigen-specific tumor immunity after DC-based vaccination support this hypothesis and provide rationale to further evaluate this approach in patients. Preliminary human studies are now required to evaluate optimal DC dose, schedule of vaccination, route of delivery, and maturational state of cultured cells. Initiation of these phase I/II cell therapy-based studies will occur in collaboration with hospital-based transfusion facilities. Issues relating to cell harvesting, storage, culture methodology, and administration require the collaborative efforts of basic scientists, immunologists, clinical investigators, and transfusion medicine staff to ensure strict quality control of injected cellular products. This review is intended to provide a brief overview of clinical DC-based gene transfer.
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PMID:Genetically modified dendritic cells in cancer therapy: implications for transfusion medicine. 1166 36

Decoy receptor 3 (DcR3), a soluble receptor belonging to the TNFR superfamily, is a receptor for both Fas ligand (FasL) and LIGHT. It has been demonstrated that DcR3 is up-regulated in lung and colon cancers, thus promoting tumor growth by neutralizing the cytotoxic effects of FasL and LIGHT. In this study, we found that DcR3.Fc profoundly modulated dendritic cell differentiation and maturation from CD14(+) monocytes, including the up-regulation of CD86/B7.2, and the down-regulation of CD40, CD54/ICAM-1, CD80/B7.1, CD1a, and HLA-DR. Moreover, DcR3-treated dendritic cells suppressed CD4(+) T cell proliferation in an allogeneic MLR and up-regulated IL-4 secretion of CD4(+)CD45RA(+) T cells. This suggests that DcR3.Fc may act not only as a decoy receptor to FasL and LIGHT, but also as an effector molecule to skew T cell response to the Th2 phenotype.
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PMID:Modulation of dendritic cell differentiation and maturation by decoy receptor 3. 1199 33

As alpha-melanocyte-stimulating hormone (alpha-MSH) is released by immunocompetent cells and has potent immunosuppressive properties, it was determined whether human dendritic cells (DCs) express the receptor for this hormone. Reverse transcription-polymerase chain reaction detected messenger RNA specific for all of the known melanocortin receptors in DCs. Mixed lymphocyte reactions also revealed that treatment with [Nle(4), DPhe(7)]-alpha-MSH (NDP-MSH), a potent alpha-MSH analogue, significantly reduced the ability of DCs to stimulate allogeneic T cells. The expression of various cell surface adhesion, maturation and costimulatory molecules on DCs was also investigated. Although treatment with NDP-MSH did not alter the expression of CD83 and major histocompatibility complex class I and II, the surface expression of CD86 (B7.2), intercellular adhesion molecule (ICAM-1/CD54) and CD1a was reduced. In summary, our data indicate that NDP-MSH inhibits the functional activity of DCs, possibly by down-regulating antigen-presenting and adhesion molecules and that these events may be mediated via the extracellular signal-regulated kinase 1 and 2 pathway.
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PMID:The melanocortin receptor agonist NDP-MSH impairs the allostimulatory function of dendritic cells. 2007 7