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

We have compared the phenotypic and functional characteristics of dendritic cells (DC) generated in vitro from the peripheral blood mononuclear fraction of myelodysplastic syndrome (MDS) patients (four refractory anaemia, four refractory anaemia with excess of blasts) with DCs generated in a similar way from eight healthy donors. After 10 d of culture in the presence of GM-CSF and IL-4, reduced numbers and percentages of DCs were obtained in MDS subjects. MDS DCs exhibited significantly lower expression of CD1a, CD54, CD80 and MHC class II molecules. Their ability to stimulate T lymphocytes in an allogeneic mixed leucocyte reaction was reduced in comparison to normal subjects. Furthermore, MDS DCs also showed a reduced receptor-mediated endocytosis as demonstrated by FITC-dextran uptake. Simultaneous fluorescence in situ hybridization (FISH) and immunophenotypic analysis demonstrated that MDS DCs have the same cytogenetic abnormality of the malignant clone. Taken together these findings indicate that, in MDS, DCs are part of the malignant clone and exhibit a deficient antigen uptake and presentation.
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PMID:Phenotypic and functional characteristics of monocyte-derived dendritic cells from patients with myelodysplastic syndromes. 1060 93

Dendritic cells (DCs) are the most efficient antigen presenting cells (APCs) that initiate and modulate our internal immune responses in stimulating both B cells to produce various antibodies and T cells to control cell-mediated immunity. Such DCs can be classified into three groups based on their origin. One is the myeloid DCs originating from CD34+ stem cells that are further differentiated into CD14+ CD1a- phagocytotic, glass-adherent macrophages with the help of M-CSF, or into CD14- CD1a+, Birbeck granule containing LAG-1+ Langerhans cells by GM-CSF, TNF-alpha and TGF-beta 1 stimulation. The latter Langerhans cells appear to differentiate into DC1 as strong stimulators of T cells displaying large amounts of MHC-peptide complexes and co-stimulatory molecules, such as B7-1 and B7-2, after capturing antigens and migrating to a regional lymphoid organ. The second group is the lymphoid DCs originating from CD4+CD11c- cells, which differentiate into DC2 when cultured with IL-3. Third is the follicular dendritic cells (FDC) observed in lymphofollicules that capture foreign antigens with their Fc-receptor or complement-receptors and keep the antigens inside the follicules. DC1s secrete IL-12, which turns CD4 T cells into Th1 cells to induce cellular immunity, whereas DC2s favor production of Th2 cells to organize humoral immunity. Therefore, DCs appear to control our internal self-defense system. These unique features of DCs enable us to manipulate Th1 and Th2 activation selectively, and thus antigen-pulsed DCs are currently thought of as excellent tools to induce specific T cell immunity towards virus-infected cells or tumor cells.
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PMID:[Dendritic cells and tumor specific immunity]. 1063 93

Dendritic cells (DC) are powerful antigen presenting cells, which have the unique capacity to stimulate naive T cells. In spite of the well-known decline of T cell function in old age, little information is available on whether DC are also affected by the aging process. This is mainly due to problems with the isolation and purification of DC. Rapid progress in the characterization of DC has been made in recent years, as simple methods to generate large numbers of DC from precursors have been developed. It was the aim of the present study to compare monocyte derived DC from old and young healthy persons. The generation of DC from blood monocytes in response to GM-CSF and IL-4 treatment was similar in cells from young and old persons. The DC population thus obtained had a typical dendritic morphology and expressed DC surface markers, such as HLA class II, CD1a, CD11c, CD54, CD80 and CD86, but not CD14 for a period of up to three weeks in culture. DC from young and old persons produced IL-12 and TNF-alpha and responded equally well to maturation-inducing stimuli. DC maturation was stimulated by purified protein derivative (PPD) of Mycobacterium tuberculosis, whole inactivated influenza virus and by influenza split vaccine, but not by purified viral RNA. When tested for their antigen-presenting capacity, DC from young and old persons were capable of stimulating the proliferation and the cytokine production of T cells. It was of particular interest that CD45RA(+) as well as CD45RO(+) T cells from aged donors were unable to respond to stimulation with influenza proteins presented by monocytes, but were triggered to proliferate and to produce cytokines when antigen was presented by DC. The results demonstrate that DC from old persons (a) may still function as powerful antigen-presenting cells provided the right differentiation and maturation stimuli are present; (b) are capable of mobilizing residual capacity in senescent T cells and (c) may therefore represent a potent tool for immunotherapy and vaccines in old age.
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PMID:Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. 1068 36

One successful approach to generate dendritic cells (DC) is to cultivate peripheral blood monocytes in fetal calf serum (FCS)-containing medium in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4. Because the use of xenogenic proteins has to be strictly avoided for clinical applications, alternative protocols use human plasma instead of FCS. The aim of our study was to characterize DC generated in the presence of human plasma; moreover, we describe a novel protocol to generate DC directly from peripheral blood mononuclear cells (PBMC). DC generated from purified monocytes in the presence of 1% human plasma (HP-DC) and GM-CSF and IL-4 both in the allogenic mixed leukocyte reaction (MLR) and in the tetanus presentation assay were potent stimulators of T-cell proliferation. DC generated from PBMC were equally effective stimulators in the allogenic MLR as those generated from purified monocytes. When the immunophenotype of DC generated from FCS containing medium (FCS-DC) was compared to that of HP-DC, the surface expression of CD1a and CD80 was significantly lower in HP-DC. In contrast, the expression of CD83 and CD86 was significantly higher in HP-DC than in FCS-DC. The capacity of receptor mediated endocytosis and macropinocytosis was found to be significantly lower in HP-DC when compared to FCS-DC. The differences in the immunophenotype, macropinocytosis and endocytosis between the HP-DC and the FCS-DC were observed independently of the generation of the cells from PBMC or purified monocytes. Our data indicate that HP-DC are potent stimulators of T-cell proliferation and exhibit a characteristic phenotype of intermediate maturity. Moreover, DC can be directly generated from PBMC preparations.
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PMID:Functional and phenotypic characteristics of dendritic cells generated in human plasma supplemented medium. 1073 10

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro. Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations. The highest yield of CD1a(+)/CD14(-) cells could be obtained with stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, GM-CSF, and FLT-3-ligand. In the AML samples the median content of CD1a(+)/CD14(-) cells after eight days of culture was 3.5% (r = 0%-82%). In five informed patients CD1a(+)/CD14(-) cells were sorted by fluorescence-activated cell sorting or immunomagnetic separation. Cytogenetic and polymerase chain reaction analyses showed known primary chromosomal aberrations (monosomy 7 and inversion 16) in the sorted fractions, respectively. Dendritic cells (DC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex beads, but stimulated allogeneic naive cord blood-derived T cells more efficiently than did uncultured blasts. In ALL patients the median percentage of CD1a(+)/CD14(-) cells was 1.2% (r = 0.7%-3.8%) after culture. The sorted CD1(+)/CD14(-) fractions were BCR/ABL-negative when analyzed with fluorescence in situ hybridization, indicating their nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.
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PMID:Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells. 1074 86

We recently demonstrated that dendritic cells (DCs) can be generated from monocytes in the presence of high concentrations of human serum (HS), provided the extra-cellular pH is maintained at plasma values. Because monocyte-derived DCs (Mo-DCs) can also be generated in the presence of fetal calf serum (FCS) or serum-free medium, we have investigated whether these different culture supplements influence DC generation. With this aim, purified monocytes were cultured with GM-CSF plus IL-4 for 6 days and were further exposed to TNF-alpha for 2 additional days, in the presence of HS, autologous plasma (AP), FCS, or X-VIVO 20, a serum-free medium. Our results show that good yields of functionally mature DCs can reproducibly be obtained in the presence of HS or AP, as assessed by CD83 and CD86 up-regulation, dextran-FITC uptake, allogeneic MLR assays and the induction of an autologous response. Interestingly, the effect of serum on DC generation was probably not only quantitative, but also qualitative, since (i) the majority of HS- or AP-cultured DCs expressed CD83 with very weak levels of CD1a, whereas CD83+ DCs cultured in FCS or X-VIVO were mostly CD1a++; (ii) HS- and AP-cultured DCs were much more granular and heterogeneous than FCS- or X-VIVO-cultured DCs, and (iii) the presence of Birbeck-like granules was preferentially observed in HS- or AP-cultured DCs, as assessed by electron microscopy. That these different cells resemble dermal DCs (DDCs) was further supported by the observations that most of the cells displayed intracytoplasmic FXIIIa in the absence of Lag antigen, and expressed E-cadherin at very low levels. Altogether, our results indicate that starting from the same monocytic population, different subsets of DCs can be generated, depending on the culture conditions. Thus, HS or AP favors the generation of fully mature DCs that resemble activated dermal DCs, whereas FCS, or X-VIVO preferentially leads to the generation of less mature CD1a++ dermal-like DCs.
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PMID:Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements. 1075 42

We studied the effects of 1alpha,25-dihydroxyvitamin D3 (1alpha, 25-(OH)2D3) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1alpha,25-(OH)2D3 up to 100 nM. DC differentiated in the presence of 10 nM 1alpha,25-(OH)2D3 (D3-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of DC maturation with LPS or incubation with CD40 ligand-transfected cells, D3-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory cell function of D3-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D3-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1alpha,25-(OH)2D3 may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.
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PMID:Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. 1077 43

It is fully anticipated that dendritic cells (DCs) will become a mainstay for inclusion in biological therapies for patients with cancer including breast cancer. To elucidate the cellular composition of DCs infiltrating human breast cancers, we investigated the correlations between the density of infiltrating DCs and some clinicopathological factors of breast cancer patients, examined cytokine expression on cancer cells and finally, assessed the numbers of CD45RO+ tumor infiltrating lymphocytes (TIL). Tissues adjacent to cancer nests contained significantly more S-100 protein+ and S-100 protein+ CD1a- DCs, but less CD1a+ DCs, than the nests. In invasive ductal carcinomas infiltration by S-100 protein+ DCs within and adjacent to nests, CD1a+ DCs within nests and S-100 protein+ CD1a- DCs adjacent to nests was denser than that in non-invasive carcinomas. With respect to the histological subtypes, there were fewer DCs in scirrhous carcinomas. Patients with stage IV disease had significantly fewer DCs of primary lesions than at other clinical stages. There were good correlations between infiltration by S-100 protein+ DCs and expression of the cytokines GM-CSF, IL-1alpha and TNF-alpha on cancer cells and between GM-CSF expression and S-100 protein+ CD1a- DCs. There was a close correlation between CD45RO+ TIL and S-100 protein+ DC densities both within and adjacent to the cancer nests and the S-100 protein+ CD1a- DC density adjacent to the cancer nests. Despite extensive immunoelectron microscopic observation, CD1a+ DCs within cancer nests contained only few Birbeck's granule-like structure. These data indicate that cancer nests are infiltrated predominantly by CD1a+ DCs, whereas S-100 protein+ CD1a- DCs predominate in surrounding tissues, and a infiltration by DCs may require cytokine expression on cancer cells and simultaneous lymphocyte infiltration. The findings of this clinicopathological study indicate the importance of evaluating simultaneously the types and localizations of infiltrating DCs in cancer tissues.
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PMID:Infiltrating dendritic/Langerhans cells in primary breast cancer. 1081 49

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

In this study, we describe human FDF03, a novel member of the Ig superfamily expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a single extracellular V-set Ig-like domain. Two potential secreted isoforms were also identified. The gene encoding FDF03 mapped to chromosome 7q22. FDF03 was mostly detected in hemopoietic tissues and was expressed by monocytes, macrophages, and granulocytes, but not by lymphocytes (B, T, and NK cells), indicating an expression restricted to cells of the myelomonocytic lineage. FDF03 was also strongly expressed by monocyte-derived dendritic cells (DC) and preferentially by CD14+/CD1a- DC derived from CD34+ progenitors. Moreover, flow cytometric analysis showed FDF03 expression by CD11c+ blood and tonsil DC, but not by CD11c- DC precursors. The FDF03 cytoplasmic tail contained two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences. When overexpressed in pervanadate-treated U937 cells, FDF03 was tyrosine-phosphorylated and recruited Src homology-2 (SH2) domain-containing protein tyrosine phosphatase (SHP)-2 and to a lesser extent SHP-1. Like engagement of the ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03 inhibited calcium mobilization in response to CD32/FcgammaRII aggregation in transfected U937 cells, thus demonstrating that FDF03 can function as an inhibitory receptor. However, in contrast to LAIR-1/p40, cross-linking of FDF03 did not inhibit GM-CSF-induced monocyte differentiation into DC. Thus, FDF03 is a novel ITIM-bearing receptor selectively expressed by cells of myeloid origin, including DC, that may regulate functions other than that of the broadly distributed LAIR-1/p40 molecule.
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PMID:FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells. 1090 17


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