UNIPROT:P06126 - FACTA Search

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Query: UNIPROT:P06126 (CD1a)
2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DCs) are potent antigen-presenting cells (APCs); they are considered to be the most important APC in the lung. Recently, the number of DCs in the large airways was demonstrated to increase in patients with atopic asthma, leading to the concept that DCs play an important role in airway inflammation. However, little is known about the distribution of lung DCs in the small airways under other pathological conditions. The aim of the present study was to examine the distribution of DCs in the bronchiolar tissues in patients with diffuse panbronchiolitis (DPB), which is a chronic inflammatory disorder of the airways histologically characterized by peribronchiolitis. We investigated the distribution of DCs in the bronchiolar tissues of the lungs in 11 patients with DPB and 7 control subjects with normal lungs using immunohistochemical methods. Marked increases in the number of CD1a(+), CD1c(+), and CD83(+) DCs were found in both the bronchiolar epithelium and submucosal tissues of patients with DPB, compared with control subjects with normal lungs. The most striking increase occurred in the number of DCs expressing CD83, a marker of mature DCs, in the submucosal tissues of patients with DPB. The increases of these positive cells in patients with DPB were more marked in the submucosal tissues than in the epithelium. The bronchiolar epithelial cells in patients with DPB strongly expressed GM-CSF protein, which is an important cytokine for the differentiation and function of DCs, suggesting that the increased local production of GM-CSF may be responsible for the accumulation and differentiation of DCs in the bronchiolar tissues of patients with DPB. These results suggest that increased DCs in the bronchiolar tissues, together with their phenotypical maturation, may play an important role in the mucosal immune response in patients with DPB through their potent antigen-presenting function.
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PMID:Increased numbers of dendritic cells in the bronchiolar tissues of diffuse panbronchiolitis. 1090 34

It has been reported previously that in vitro treatment of human blood derived dendritic cells (DC) with contact allergens provokes the elevated expression of mRNA for interleukin (IL) 1beta, under conditions where similar treatment of cells with the non-sensitizing skin irritant sodium lauryl sulfate (SLS) did not alter IL-1beta mRNA levels (Reutter et al., 1997). The purpose of the present investigation was to evaluate further this phenomenon and to explore the potential utility of this approach for the purpose of skin sensitization testing. Human peripheral blood progenitor cells prepared from healthy adult volunteers were cultured in the presence of IL-4 and granulocyte/macrophage colony stimulating factor. After 5 days of culture, the majority of cells had a Langerhans cell-like phenotype, with characteristic dendritic morphology and cell surface expression of CD83, major histocompatibility complex class II and CD1a determinants. These blood-derived DC were cultured in the presence of the contact allergen 2,4-dinitrofluorobenzene (DNFB), SLS or vehicle alone and mRNA expression for IL-1beta, IL-6 and IL-18 was analysed by semiquantitative reverse transcriptase polymerase chain reaction. Constitutive expression of all three cytokines was observed for DC isolated from all donors examined. Exposure to DNFB resulted in upregulation of IL-1beta mRNA (two- to threefold) in cells derived from three out of eight donors whereas IL-6 and IL-18 were largely unaffected by allergen exposure. In contrast, SLS treatment did not induce IL-1beta mRNA expression in any of the donors investigated. Analysis of cytokine mRNA expression using the protocol described by Reutter et al. (1997), did not increase the sensitivity of measurement of induced cytokine expression. Although selected upregulation of IL-1beta by blood derived DC has been confirmed, a wider range of contact allergens and irritants need to be assessed before this approach could be considered for hazard identification.
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PMID:Investigation of induced changes in interleukin 1beta mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. 1090 42

As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting cell. This functional change is accompanied by a change in DC immunophenotype. The signal transduction events underlying this process are poorly characterized. In this study, we have investigated the signal transduction pathways involved in the lipopolysaccharide (LPS)-induced maturation of human monocyte-derived DCs (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the p38 stress-activated protein kinase (p38SAPK), extracellular signal-regulated protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear factor (NF)-kappaB pathways. Studies using inhibitors demonstrate that PI3 kinase/Akt but not the other pathways are important in maintaining survival of LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up-regulation of CD80, CD83, and CD86, but did not have any significant effect on the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression. Inhibiting the NF-kappaB pathway significantly reduced the LPS-induced up-regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and NF-kappaB pathways simultaneously had variable effects depending on the cell surface marker studied. It thus appears that different aspects of LPS-induced MoDC maturation are regulated by different and sometimes overlapping pathways.
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PMID:The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells. 1091 Sep 20

The therapeutic use of dendritic cells (DC) in antigen-specific anti-tumor vaccines, requires sufficient numbers of functional DC, the preparation of which should comply with the code of Good Manufacturing Practice. In addition, the expression of tumor specific antigen should be possible in these DC. As a preclinical step, the method reported here was developed in healthy volunteers. Monocytes (Mo) were isolated by leukapheresis from 12 donors, purified by elutriation and then cultured for 6 days in sealed bags in AIM-V serum free medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13). Between 6x10(8) and 1x10(9) immature DC (iDC) could be differentiated from one leukapheresis. Cells displayed a characteristic iDC phenotype (CD1a(+), CD14(-), CD80(+), CD86(+), HLA DR(+), CD83(-)), and had potent allogeneic and antigen dependent autologous T cell-stimulatory capacity. Moreover, iDC could be further differentiated into mature DC by CD40 ligation as assessed by CD83 expression and the upregulation of HLA-DR and costimulatory molecules. After infection with a recombinant adenovirus encoding for beta-galactosidase (betaGal), 50% to 80% of iDC expressed betaGal without toxicity. Adenovirus infection increased the expression of both costimulatory molecules and CD83, and also increased allogeneic stimulatory capacity. Thus, the method developed here allows us to use large numbers of functional iDC as will be required for therapeutic uses in man. These DC can express a transgenic protein.
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PMID:Adenoviral transduction of human 'clinical grade' immature dendritic cells enhances costimulatory molecule expression and T-cell stimulatory capacity. 1091 50

In the present study, we show that endothelial-like cells (ELCs) can develop from human CD14-positive mononuclear cells (CD14 cells) in the presence of angiogenic growth factors. The CD14 cells became loosely adherent within 24 h of culture and subsequently underwent a distinct process of morphological transformation to caudated or oval cells with eccentric nuclei. After 1 week in culture the cells showed a clear expression of endothelial cell markers, including von Willebrand factor (vWF), CD144 (VE-cadherin), CD105 (endoglin), acetylated low-density lipoprotein (AC-LDL)-receptor, CD36 (thrombospondin receptor), FLT-1, which is vascular endothelial cell growth factor (VEGF) receptor-1, and, to a weaker extent, KDR (VEGF receptor-2). Furthermore, in these cells structures resembling Weibel-Palade bodies at different storage stages were identified by electron microscopy, and upon culturing on three-dimensional fibrin gels the cells build network-like structures. In addition, cell proliferation and vWF expression was stimulated by VEGF, and the endothelial cell adhesion molecules CD54 (ICAM-1), and CD106 (VCAM-1) became transiently inducible by tumor necrosis factor-alpha (TNF-alpha). In contrast, the dendritic markers CD1a, and CD83 were not expressed to any significant extent. The expression of CD68, CD80 (B7-1), CD86 (B7-2), HLA-DR and CD36 may also suggest that ELCs might be related to macrophages, sinus lining or microvascular endothelial cells. Taken together, our observations indicate that ELCs can differentiate from cells of the monocytic lineage, suggesting a closer relationship between the monocyte/macrophage- and the endothelial cell systems than previously supposed.
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PMID:Endothelial-like cells derived from human CD14 positive monocytes. 1092 8

We previously reported an increased percentage of CD14+CD16++ monocytes in the peripheral blood of HIV-infected patients but the physiopathological role of this monocyte subset remains unclear. Cells with a CD14+CD16++ phenotype may be obtained in vitro by culturing human peripheral blood monocytes in the presence of GM-CSF, IL-4 and IL-10. In the present study, we compared the phenotypic and functional characteristics of monocytes-derived CD14+CD16++ cells with those of macrophages and dendritic cells. We show that the CD14+CD16++ cells express dendritic cell markers: CD40, CD80, CD86, HLA-DR, CD11b, CD11c, CD18, CD1a, and CD83. Using RNase protection assay, we demonstrate that CD14+CD16++ cell subset expresses a low ratio of IL-1beta/IL-1ra mRNA and expresses IL-6, MIP-1alpha, MIP-1beta, MCP-1, IL-8, RANTES and I-309 transcripts, similar to dendritic cells. CD14+CD16++ cells produce IL-12, MCP-1 and IL-8, as assessed by flow cytometry. Moreover, CD14+CD16++ cells pulsed with different recall antigens induce a potent autologous T cell proliferation. Altogether, these results provide evidence that CD14+CD16++ cells differentiated in vitro from peripheral blood monocytes exhibit dendritic cell characteristics.
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PMID:CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit phenotypic and functional dendritic cell-like characteristics. 1094 Aug 76

Peripheral blood mononuclear cells (PBMCs) from 15 newly diagnosed acute myeloid leukemia (AML) patients were cultured in fetal calf serum-free media supplemented with either granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor alpha (TNFalpha), or GM-CSF, stem cell factor (SCF), TNFalpha and transforming growth factor beta (TGFbeta) in order to generate leukemia-derived dendritic cells (DCs). Cultured cells were analyzed by flow cytometry with respect to DC-associated surface molecules (CD1a, CD83, CD40, CD80, CD86, HLA-DR) when they showed significant DC morphology in culture (14 cases). After cultivation, neo-expression or upregulation of CD1a antigen was found in 8 samples, CD83 in 2, CD40 in 14, CD80 in 7, and CD86 in 9. Twelve of 14 AMLs, in which DC morphology could be induced upon cultivation, showed upregulation of at least 2 DC-associated molecules. For induction of DC differentiation. GM-CSF, IL-4 plus TNFalpha was superior in 11 cases, and better results were obtained with GM-CSF, SCF, TNFalpha plus TGFbeta in 3 cases. In 7 of 14 samples tested, a marked increase of the T-cell stimulatory capacity could be demonstrated in the allogeneic mixed lymphocyte reaction. The leukemic origin of in vitro-generated DCs was demonstrated by fluorescence in situ hybridization in a patient with translocation t(15;17). Our results suggest that the use of different culture conditions may extend the number of AML patients in which a differentiation towards the DC lineage can be induced in vitro.
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PMID:Culture requirements for induction of dendritic cell differentiation in acute myeloid leukemia. 1096 83

HLA-DM has been known to be largely absent from the cell surface of antigen-presenting cells, accumulating instead in the intracellular compartment. In this study, we demonstrated that a population of HLA-DM-positive (HLA-DM+) dendritic cells (DCs) can be identified in an in vitro culture of CD34+ bone marrow haematopoietic stem cells. CD34+ bone marrow cells of healthy donors were used to generate DCs with the recombinant human cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor alpha (TNF-alpha) and stem cell factor (SCF), both with and without interleukin 4 (IL-4). Flow cytometric analysis demonstrated that HLA-DM+ cells comprised 2.5 +/- 0.9% and 1.8 +/- 0.4% of the CD34+ cell-derived progeny in the presence of GM-CSF, TNF-alpha and SCF after 7 d and 14 d of culture respectively. The number of HLA-DM molecules expressed per HLA-DM+ cell on d 7 was significantly higher than that on d 14 (1410 +/- 47 versus 370 +/- 25, P < 0.05). The addition of IL-4 to the cytokines from the commencement of culture increased the proportion of HLA-DM+ cells and increased the number of HLA-DM molecules per HLA-DM+ cell significantly (P < 0.05). Although most of the HLA-DM+ cells expressed CD1a, CD80 or CD86 antigen, only a small proportion of CD1a+, CD80+ or CD86+ cells expressed HLA-DM. About half the HLA-DM+ cells expressed CD83. The addition of IL-4 resulted in a decrease in the expression of CD83 on the HLA-DM+ cells on d 7. Microscopic evaluations of sorted HLA-DM+ cells revealed the characteristic morphological features of DCs. Primary mixed lymphocyte cultures demonstrated that the HLA-DM+ cells elicited a vigorous proliferation of allogeneic T cells. The level of antigen-specific T-cell activation induced by antigen-pulsed, chloroquine-treated HLA-DM+ cells was substantially higher than that induced by HLA-DM- cells (P < 0.05). These results show that HLA-DM can be used as a useful DC lineage-specific marker, as well as a tool for the characterization of DCs and human immunotherapy.
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PMID:Surface expression of HLA-DM on dendritic cells derived from CD34-positive bone marrow haematopoietic stem cells. 1097 96

Although dendritic cells (DC) can be cultured from cord blood (CB) CD34+ progenitor cells, the generation of DC from CB monocytes has not been reported. In this paper, we explored the generation of DC from CB monocytes to establish the simplest way to obtain a substantial number of DC from CB. We isolated monocytes from CB mononuclear cells (CB-MNC) by the plastic adherence method. These adherent cells (monocyte-rich cells) were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) or in serum-free X-VIVO 15 medium (SFM) for 7 days, both of which contained 100 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml interleukin-4 (IL-4) with or without 10 ng/ml tumor necrosis factor-alpha (TNF-alpha) (added at day 5). In the presence of GM-CSF and IL-4, CB-adherent cells became nonadherent, acquired DC morphology, and showed increased expression of CD1a, CD80, CD86, and HLA-DR; they lost membrane CD14 and some cells with the expression of CD83 and CMRF-44 were generated. With the addition of TNF-alpha to these cultures and culturing for further 2 days, the proportion of CD83+ cells was elevated in both the FBS and SFM culture systems, compared with the culture without TNF-alpha. In the culture with TNF-alpha, cells expressing CD1a, CD80, CD86, HLA-DR, and HLA-DQ were markedly increased. TNF-alpha-treated cells were demonstrated to be stronger stimulators for proliferation of both allogeneic CB lymphocytes and PB lymphocytes than were cells not treated with TNF-alpha. The yield of CD83+ DC at day 7 of cultures was 4.9 +/- 1.1 x 10(5) or 3.0 +/- 0.5 x 10(5) per 1.2 x 10(7) CB-MNC plated initially when cultured in FBS or SFM, respectively. These results have shown that a substantial number of mature DC could be generated from CB-adherent cells even by serum-free culture. We then compared these CB-adherent cell-derived DC (CB-DC) with peripheral blood (PB)-adherent cell-derived DC (PB-DC) in cell-surface phenotype and function. We found day 7 CB-DC have lower expression of CD80, CD1a, CD83, and CMRF-44 than day 7 PB-DC, but CB-DC have a similar capacity to stimulate the proliferation of both allo-CB lymphocytes and PB lymphocytes, compared with PB-DC. CB-DC cultured with GM-CSF and IL-4 have almost identical capacity of phagocytosis to take up fluorescein isothiocyanate (FITC)-dextran and Lucifer yellow (LY), compared with PB-DC. In summary, our findings suggest CB adherent cells, when cultured with GM-CSF, IL-4, and TNF-alpha, are a potent source of functional DC. Thus, CB-DC as well as PB-DC may become valuable tools for immunotherapy.
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PMID:Generation of dendritic cells from adherent cells of cord blood by culture with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha. 1098 43

To generate mature and fully functional CD83(+) dendritic cells derived from circulating CD14(+) cells highly purified from the leukapheresis products of multiple myeloma patients.CD14(+) monocytes were selected by high-gradient magnetic separation and differentiated to immature dendritic cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 6-7 days and then induced to terminal maturation by the addition of tumor necrosis factor-alpha or stimulation with CD40 ligand. Dendritic cells were characterized by immunophenotyping, evaluation of soluble antigens uptake, cytokine secretion, capacity of stimulating allogeneic T cells, and ability of presenting nominal antigens, including tumor idiotype, to autologous T lymphocytes. Phenotypic analysis showed that 90% +/- 6% of cells recovered after granulocyte-macrophage colony-stimulating factor and interleukin-4 stimulation expressed all surface markers typical of immature dendritic cells and demonstrated a high capacity of uptaking soluble antigens as shown by the FITC-dextran assay. Subsequent exposure to maturation stimuli induced the downregulation of CD1a and upregulation of CD83, HLA-DR, costimulatory molecules and induced the secretion of large amounts of interleukin-12. Mature CD83(+) cells showed a diminished ability of antigen uptake whereas they proved to be potent stimulators of allogeneic T cells in a mixed lymphocyte reaction. Monocyte-derived dendritic cells, pulsed before the addition of maturation stimuli, were capable of presenting soluble proteins such as keyhole limpet hemocyanin and tetanus toxoid to autologous T cells for primary and secondary immune response, respectively. Conversely, pulsing of mature (CD83(+)) dendritic cells was less efficient for the induction of T-cell proliferation. More importantly, CD14(+) cells-derived dendritic cells stimulated autologous T-cell proliferation in response to a tumor antigen such as the patient-specific idiotype. Moreover, idiotype-pulsed dendritic cells induced the secretion of interleukin-2 and gamma-interferon by purified CD4(+) cells. T-cell activation was better achieved when Fab immunoglobulin fragments were used as compared with the whole protein. When dendritic cells derived from CD14(+) cells from healthy volunteers were analyzed, we did not find any difference with samples from myeloma patients as for cell yield, phenotypic profile, and functional characteristics. These studies demonstrate that mobilized purified CD14(+) cells represent the optimal source for the production of a homogeneous cell population of mature CD83(+) dendritic cells suitable for clinical trials in multiple myeloma.
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PMID:Efficient presentation of tumor idiotype to autologous T cells by CD83(+) dendritic cells derived from highly purified circulating CD14(+) monocytes in multiple myeloma patients. 1098 94

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