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)

Dendritic cells (DCs) consist of a heterogeneous population of hematopoietic cells characterized by their unique dendritic morphology, their efficient antigen-presenting capability to activate naive CD4(+) and CD8(+) T cells, and their lack of lineage specific markers. Functional properties comparing umbilical cord blood monocyte-derived and umbilical cord blood stem cell-derived DCs have not yet been investigated. CD14(+) monocytes and CD34(+) stem cells were isolated from human umbilical cord blood and were induced to differentiate into dendritic cells using 100 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF), 25 ng/mL IL-4, 2.5 ng/mL tumor necrosis factor-alpha (TNF-alpha), 100 ng/mL GM-CSF, 25 ng/mL stem cell factor, and 2.5 ng/mL TNF-alpha, respectively. Flow cytometric analysis revealed that the 14-day-old dendritic cells were CD80(+), CD86(+), CD83(+), CD54(+), CD1a(+), CD11b(+), CD11c(+), HLA-DR(+), CD34(-), CD3(-), CD19(-), CD14(-), and CD16(-). Reverse transcription polymerase chain reaction was employed to detect expression of mRNA for CD80 and CD86. Differentiating monocytes initially expressed CD86 while CD80 appeared on day 2. Differentiating stem cells expressed CD80 and CD86 on day 2 of culture. The surface expression of CD80 and CD86 was studied over the course of differentiation. Mixed lymphocyte reaction was employed to evaluate the two types of lineage-derived DCs. Prior to the functional assay, CD14(+) and CD34(+) derived DCs were stimulated for 18 h with 0.1 mg/mL and 1.0 mg/mL E. coli lipopolyssacharide, respectively. Monoclonal antibodies (mabs) to CD80 and CD86 were employed to assess their costimulatory roles. A decrease of stimulation as depicted by decreased T cell activation was significant with mabs to both CD80 and CD86 on monocyte-derived DCs while only mabs to CD86 induced decreased T cell activation by stem cell-derived DCs. The varied functional role of CD80 and CD86 costimulatory molecules is associated with DC differentiation from distinct cord blood isolated hematopoietic lineages. These studies demonstrate that DC association with distinct hematopoietic lineages is of relevance in transplantation and vaccine therapies.
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PMID:Costimulatory function of umbilical cord blood CD14+ and CD34+ derived dendritic cells. 1283 22

CD34+ cell-derived hematopoietic precursors amplified with FLT3-ligand, thrombopoietin and stem cell factor became, after a 6-day induction with GM-CSF, IL-4 and TGF-beta1, HLA-DR+, CD1a+, CD83-, CD86-, CD80- cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-alpha added for the last 3 days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin+CD83- LC. Langerin+CD83+ and Langerin+CD83- cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a-CD14- and CD1a-CD14+ cells sorted from FLT3-ligand, thrombopoietin and stem cell factor cultures responded to TNF-alpha by an increase of Langerin+ cells. Thus, TNF-alpha rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGF-beta1 containing-cultures, LPS or IL-1beta also induced significant numbers of Langerin+CD83- immature cells displaying a low allostimulatory activity, while CD40-ligand largely promoted highly allostimulatory Langerin-CD83+ cells. Altogether, these data show that in contrast to CD40-ligand, which induced LC maturation even in presence of TGF-beta1, nonspecific proinflammatory factors such as TNF-alpha, IL-1 or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF-beta1.
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PMID:TNF-alpha induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14-CD1a and CD14+CD1a- precursors derived from CD34+ cord blood cells. 1288 72

GM-CSF stimulates the growth and differentiation of hematopoietic progenitors and also affects mature cell function. These effects have led to the use of GM-CSF as a vaccine adjuvant with promising results; however, the mechanisms underlying GM-CSF-mediated immune potentiation are incompletely understood. In this study, we investigated the hypothesis that the immune stimulatory role of GM-CSF is in part due to effects on class II MHC Ag presentation. We find that, in primary human monocytes treated for 24-48 h, GM-CSF increases surface class II MHC expression and decreases the relative level of the invariant chain-derived peptide, CLIP, bound to surface class II molecules. GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16. Furthermore, GM-CSF-treated monocytes are better stimulators in a mixed leukocyte reaction. Additional analyses of the class II pathway revealed that GM-CSF increases total protein and RNA levels of HLA-DR, DM, and DOalpha. Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF. Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter. Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CIITA.
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PMID:Regulation of the class II MHC pathway in primary human monocytes by granulocyte-macrophage colony-stimulating factor. 1292 84

IFN-alpha is an important cytokine for the generation of a protective T cell-mediated immune response to viruses. In this study, we asked whether IFN-alpha can regulate the functional properties of dendritic cells (DCs). We show that monocytes cultured in the presence of GM-CSF and IFN-alpha can differentiate into DCs (IFN-alpha-derived DCs (IFN-DCs)). When compared with DCs generated in the presence of GM-CSF and IL-4 (IL-4-derived DCs), IFN-DCs exhibited a typical DC morphology and expressed, in addition to DC markers CD1a and blood DC Ag 4, a similar level of costimulatory and class II MHC molecules, but a significantly higher level of MHC class I molecules. After maturation with CD40 ligand, IFN-DCs up-regulated costimulatory, class I and II MHC molecules and expressed mature DC markers such as CD83 and DC-lysosome-associated membrane protein. IFN-DCs were endowed with potent functional activities. IFN-DCs secreted large amounts of the inflammatory cytokines IL-6, IL-10, TNF-alpha, IL-1beta, and IL-18, and promoted a Th1 response that was independent of IL-12p70 and IL-18, but substantially inhibited by IFN-alpha neutralization. Furthermore, immature IFN-DCs induced a potent autologous Ag-specific immune response, as evaluated by IFN-gamma secretion and expansion of CD8(+) T cells specific for CMV. Also, IFN-DCs expressed a large number of Toll-like receptors (TLRs), including acquisition of TLR7, which is classically found on the natural type I IFN-producing plasmacytoid DCs. Like plasmacytoid DCs, IFN-DCs could secrete IFN-alpha following viral stimulation or TLR7-specific stimulation. Taken together, these results illustrate the critical role of IFN-alpha at the early steps of immune response to pathogens or in autoimmune diseases.
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PMID:IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities. 1450 Jun 32

Dendritic cells (DCs) are a heterogeneous population of cells of fundamental importance in initiating innate as well as specific immune responses. The identity and function of DCs in the cat are unknown, although they are likely pivotal in the response to infection. In this study, feline DCs were derived by 3-10-day culture of adherent blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) in the presence of IL 4 and GM-CSF. BMMC consistently yielded a greater number of DCs than PBMC, and there were fewer macrophages than DC from both compartments. DCs expressed a distinct constellation of surface molecules, which included CD1a, CD1b, and CD1c, CD11b, CD14, and 2-3-fold higher levels of MHC class I and II molecules than co-cultured macrophages or fresh blood monocytes. DCs displayed typical cytoplasmic processes, limited non-specific esterase activity, and acquired antigen by phagocytosis, pinocytosis, and binding to specific receptors. Cytokine-exposed cells induced proliferation of allogeneic lymphocytes. Thus, the cells derived by these culture conditions had markers and functions analogous to immature myeloid DCs. Availability of feline DCs will enable investigation of their role in infectious disease and their potential therapeutic application.
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PMID:Immunophenotype and functional properties of feline dendritic cells derived from blood and bone marrow. 1452 31

Several laboratories have developed culture systems that allow the generation of large numbers of human dendritic cells (DC) from monocytes using granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-4 (IL-4). In this work we provided evidence that GM-CSF (100 ng/ml) in combination with a low concentration of IL-4 (5 ng/ml) was efficient in the generation of immature, non-adherent, monocyte-derived DC as the same concentration of GM-CSF, and ten times higher concentration of IL-4 (50 ng/ml). This conclusion was based on the similar phenotype profile of DC, such as the expression of CD1a, CD80, CD86, and HLA-DR, down-regulation of CD14, and the absence of CD83, as well as on their similar allostimulatory activity for T cells. A higher number of cells remained adherent in cultures with lower concentrations of IL-4 than in cultures with higher concentrations of the cytokine. However, most of these adherent cells down-regulated CD14 and stimulated the proliferation of alloreactive T cells. In contrast, adherent cells cultivated with GM-CSF alone were predominantly macrophages, as judged by the expression of CD14 and the inefficiency to stimulate alloreactive T cells. DC generated in the presence of lower concentrations of IL-4 had higher proapoptotic potential for the Jurkat cell line than DC differentiated with higher concentrations of IL-4, suggesting their stronger cytotoxic, anti-tumor effect.
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PMID:Differentiation of human dendritic cells from monocytes in vitro using granulocyte-macrophage colony stimulating factor and low concentration of interleukin-4. 1460 30

Primary immune responses are initiated by dendritic cells (DC) that inform naive T helper cells about invading pathogens. DC undergo sequential events leading to irreversible maturation upon bacterial stimulation. To investigate the responses of DC during periodontal infection, we studied the effects of LPS from Porphyromonas gingivalis on DC. DC generated from human peripheral monocytes by culture with IL-4 and GM-CSF were incubated with P. gingivalis LPS (Pg LPS) or Escherichia coli LPS (Ec LPS). Flow cytometry and real-time quantitative RT-PCR analysis revealed that Pg LPS, but not Ec LPS, preferentially up-regulated CD14 and CD16 expression at protein and mRNA levels. Furthermore, Pg LPS preferentially induced the secretion of soluble CD14. CD1a, HLA-DR and CD54 were highly expressed on DC stimulated with both kinds of LPS; however, CD40, CD80, CD83 and CD86 expression on Pg LPS-stimulated DC was lower than on Ec LPS-stimulated DC. With regard to IL-6, IL-8, IL-10, IL-12 and RANTES production from DC and allogeneic T cell proliferation, Pg LPS was a weaker stimulator than Ec LPS. These results suggested that Pg LPS triggers maturation of DC with unique characteristics, which exhibited weak immunostimulatory activity and may contribute to induction of chronic inflammation at the site of periodontal infection.
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PMID:Porphyromonas gingivalis lipopolysaccharides induce maturation of dendritic cells with CD14+CD16+ phenotype. 1511 79

In the present study, we analyzed the phenotypic alterations induced by several allergens on immature dendritic cells (DC), with the aim to develop a potential in vitro alternative for predicting the sensitizing potential of chemicals. DC were generated from human monocytes cultured in the presence of GM-CSF, IL-4 and TGF-beta1 and treated for 2 or 4 days with different chemicals. Surface marker expression (HLA-DR, CD1a, CD40, CD54, CD83, CD86, CCR7 and E-cadherin) was analyzed by flow cytometry. Results showed that a 2-day treatment with the representative allergens DNCB and NiSO(4) induced significant changes of most antigens while other chemicals such as balm of Peru (strong allergen), kathon (moderate allergen), cinnamic aldehyde (mild allergen) or the irritant SLS had no significant effect. In contrast, the 4-day treatment with allergens substantially improved the results. Indeed, despite a large variability according to the donors, the number of modified antigens was significantly higher with all the tested chemicals, except kathon, as compared to that observed with the irritant SLS. The present study indicates that, in this model, the screening of mild or moderate allergens requires both the consideration of many antigens and a prolonged time of incubation with the chemicals.
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PMID:Moderate skin sensitizers can induce phenotypic changes on in vitro generated dendritic cells. 1513 Jun 7

The aim of this work was to study the influence of nitric oxide (NO) in the differentiation of human monocytes to dendritic cells. Human monocytes from healthy donors were differentiated to immature dendritic cells in presence of GM-CSF and IL-4. Maturation of dendritic cells was achieved with GM-CSF and TNF-alpha. Nitric oxide donors (SIN-1, DEA-NO or DETA-NO) were added during differentiation of monocytes to dendritic cells and also during dendritic cells maturation. Immature dendritic cells showed a characteristic phenotype CD80+ CD1a+ HLA-DR+ CD86+ CD40+ CD14(low/-), different from adherent monocytes CD80- CD1a- HLA-DR+ CD86+ CD40- CD14++. The addition of SIN-1 the first day of monocyte differentiation reduced cell viability and increased the percentage of apoptotic immature dendritic cells. Peroxynitrite donor, SIN-1, produced more toxic effects than DEA-NO or DETA-NO. An increase in the subpopulation CD1a+ CD80+ HLADR+ of immature dendritic cells was observed when SIN-1 or DEA-NO, but not DETA-NO, was added at the beginning of monocyte culture. There was a significant reduction in the expression of TNF-alpha receptor of mature dendritic cells when SIN-1 and DEA-NO were added together GM-CSF and TNF-alpha at the beginning of maturation. The presence of SIN-1, DEA-NO or DETA-NO in maturation induced an increase of CD83+ cells. These results suggest that nitric oxide affects differentiation and maturation of dendritic cells and this effect depends on the nitric oxide donor used.
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PMID:Effect of nitric oxide in the differentiation of human monocytes to dendritic cells. 1513 4

This paper presents an improved method of isolating, culturing and cryopreserving human monocytes in large quantity with high purity using standard laboratory centrifuges. Monocytes were isolated from 300 to 360 ml of heparinized human blood using a Double Density technique employing Ficoll Isopaque and 46% iso-osmotic Percoll. Yields of monocytes ranged from 75 to 205 million (from 300 to 360 ml of blood) with an average purity of 90.6%. The ability of fresh or frozen monocytes to adhere to endothelial cells in the presence of oxidized L-alpha-1-palmitoyl-2-arachidonosyl-sn-glycero-3-phosphocholine (oxPAPC) or lipopolysaccharide (LPS) did not differ and no significant difference in response to the chemotactic stimulant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) was observed. We define a useful method for the culture and differentiation of fresh or frozen monocytes isolated by this method, into macrophages as judged by morphology, expression of the macrophage marker SRA-1 and induction of inflammatory genes TNF-alpha, IL-6 and COX-2. Also, fresh or frozen Double Density isolated cells can be successfully differentiated into dendritic cells in the presence of GM-CSF and IL-4 as judged by the expression of the hallmark surface proteins CD1a and DC-sign and the absence of CD14. This method also yields a pure population of lymphocytes.
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PMID:Method for large scale isolation, culture and cryopreservation of human monocytes suitable for chemotaxis, cellular adhesion assays, macrophage and dendritic cell differentiation. 1518 91


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