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)

Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.
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PMID:IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. 948 15

Hematopoietic cells and their progenitors play important roles in human cytomegalovirus latency and reactivation. Latent infection has been evaluated in defined populations of myeloid-lineage-committed progenitor cells coexpressing CD33 and CD15 or CD33 and CD14 along with the dendritic cell markers CD1a and CD10. These CD33+ cell populations were found to support latency and expression of viral latency-associated transcripts and to undergo reactivation of productive viral replication when differentiated in the presence of human fibroblasts. Reactivation was also observed when myeloid cells were carried in the presence of fibroblast-conditioned medium or medium supplemented with certain cytokines (interferon gamma, tumor necrosis factor alpha, interleukin 4, or granulocyte-macrophage colony-simulating factor), suggesting that cell differentiation pathways act as determinants of reactivation. More primitive CD34+ hematopoietic cells were also found to be susceptible to viral infection and latency was maintained as these cells differentiated into CD33+-lineage-committed populations. Between 0.01% and 0.001% of CD33+ CD14+ or CD33+ CD15+ bone marrow mononuclear cells isolated from naturally infected individuals were found to express latent transcripts. Thus, cytomegalovirus is carried within a small percentage of myeloid and dendritic cell progenitors in the healthy seropositive host. Virus reactivation may be triggered by factors associated with the inflammatory response.
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PMID:Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. 952 Apr 71

In human tissues different populations of dendritic cells (DC) emerge from hematopoietic progenitor cells (HPC) in the bone marrow, with the intermediate steps of differentiation not being completely understood. In vitro, DC can be directly obtained from HPC or from blood monocytes (MO) cultured in the presence of GM-CSF and additional cytokines. We compared the antigenic profile of DC derived from either MO or HPC and studied their capacity to stimulate naive lymphocytes (LY) in the allogeneic mixed lymphocyte reaction. Both types of DC expressed high levels of CD1a, MHC class II, CD80, CD86 and CD40 and were potent stimulators of LY proliferation. DC of HPC origin, though, induced a stronger mixed lymphocyte reaction than MO-derived DC and showed a slightly higher average expression of costimulatory antigens. Low-level expression of CD14 did not negatively correlate with DC function on DC stimulated with lipopolysaccharide and was even slightly higher expressed on DC differentiating from HPC than on DC from CD14+ MO.
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PMID:Comparative analysis of dendritic cells derived from blood monocytes or CD34+ hematopoietic progenitor cells. 956 69

Tumor vaccination with dendritic cells (DC) presenting tumor antigens to T cells is a promising approach in immunotherapy. The aim of this study was to enhance T cell stimulatory ability of human DC by retroviral expression of the interleukin-7 (IL-7) gene. IL-7 has been shown to provide a potent costimulatory signal for the proliferation of T cells and the generation of cytotoxic T cells (CTL). DC were generated from human peripheral blood mononuclear cells (PBMC). DC were analyzed by light- and electron-microscopy, immunophenotype (CD1a+, CD14-, CD80+, CD86+, HLA-DR+) and functional assays. According to these criteria, 75-85% of the cells were DC. The cells did not produce measurable amounts of IL-7 spontaneously nor did they express the IL-7 receptor. A retroviral IL-7 expression vector was constructed. Retroviral infection was performed with either the LXSN-hIL-7 vector of its variant LXSN. Using the LXSN-hIL-7 vector, IL-7 production of 2296 pg/10(6) cells/24 h could be achieved on average. Transduction of DC was confirmed by RT-PCR in a CD1a-enriched cell fraction. Transduction efficiency by a control virus coding for beta-galactosidase was about 30%. In autologous mixed lymphocyte reaction (MLR), IL-7 transduced DC augmented T cell proliferation by a factor of two compared with unmodified or mock-transfected DC, and in allogeneic MLR there was a 2.7-fold increase in T cell proliferation. The increase in T cell proliferation could be correlated to IL-7 secretion by DC. Dendritic cells that have been simultaneously peptide-loaded and gene-modified to secrete IL-7 are a potential tool to amplify activation of tumor-specific T cells.
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PMID:Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation. 957 47

Dendritic cells (DC) are the most effective cells for antigen presentation in primary immune responses. Human cord blood CD34+ progenitors cultured in the presence of GM-CSF and TNF alpha generate a heterogeneous population of DC including Langerhans-like DC (LLDC) and monocytes. We describe here that IL-4 exerts different effecs in such culture according to the cells considered. Thus, IL-4 favors DC components at the expense of monocytic development, and permits long-time persistence of DC which can be maintained up to one month in culture. These results show an IL-4-dependent inhibition of proliferation and emergence of CD14+ cells. Notably, however, IL-4 also acts on the DC precursors. Thus, IL-4 enhances survival and delays maturation of LLDC from CD1a+ CD14- precursors. In addition, IL-4 also favors orientation of CD14+ CD1a- DC/monocyte precursors towards dermal-type CD1a+ DC. DC recovered from IL-4 treated cultures display reduced allostimulatory capacity, but this function is restored upon IL-4 weaning. Finally, a short (48h) IL-4 pulse is sufficient to favor DC development. The present study demonstrates that IL-4 positively regulates DC development at several levels on distinct precursor cells.
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PMID:IL-4 addition during differentiation of CD34 progenitors delays maturation of dendritic cells while promoting their survival. 958 60

Epithelia-associated dendritic cells (DC) including Langerhans cells in the skin (LC) are precursors of lymph node located interdigitating DC (iDC). CD1a+ LC are known to be derived from CD34+ haemopoietic progenitor cells (HPC); however, cells of an intermediate differentiation state that are CD34- and CD1a- have not been identified. Monitoring the differentiation pathway of HPC in the presence of GM-CSF+IL-4, we observed the emergence of a distinct LC precursor population that was CD33+ CD13+ CD4+ CD38+ CD44+ CD34- CD14- CD1a-. The cells could be separated by FACS due to a unique CD44/CD38 expression pattern or by CD44 expression in conjunction with the SSC profile. It was found that they were similarly generated in the presence of GM-CSF alone and were detectable in culture for at least a week. Irrespective of being generated in the presence of GM-CSF+IL-4 or GM-CSF alone, CD44/SSC-sorted precursor cells matured to MHC class II compartments (MIIC) and Birbeck granules (BG) expressing LC, when subsequently cultured in the presence of GM-CSF+IL-4. When IL-4 was omitted, however, the same cells matured to phagocytically active adherent macrophages (Mphi). These culture conditions were associated with a > 4-fold increase in the concentration of IL-6 when compared to those used for LC differentiation. The identification of a distinct oligopotent precursor cell population that can deliberately be induced to give rise to BG+ MIIC+ CD1a+ CD14- LC or to adherent CD14+ Mk further substantiates the close relationship of monocytes and DC and may help to identify its in vivo equivalent.
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PMID:GM-CSF promotes differentiation of a precursor cell of monocytes and Langerhans-type dendritic cells from CD34+ haemopoietic progenitor cells. 960 15

We examined the effects of different cytokine combinations and culture conditions on the expansion and modulation of cell surface antigens of CD34+ derived dendritic cells (DCs), the most efficient antigen-presenting cells capable of stimulating resting T cells in the primary immune response. Cells with a dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha, TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2 weeks of culture). CD34+ cells were also grown under continuous flow conditions in an artificial capillary system: after 14d of culture, the expansion in the total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/- 4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher, whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In continuous perfusion cultures, low levels of DC precursors and of LTC-IC were still present up to day 14. The DCs generated under flow conditions stimulated the mixed leucocyte reaction (MLR) more than the cells grown in static cultures. By electron microscopy, cells grown in the continuous flow system showed an increased number of large cells with numerous dendritic processes and abundant multilamellar complexes. The cells expanded under these conditions were sorted on the basis of their light-scatter properties into two fractions: one containing a predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal complexity (mature DCs); the second including 'small cells' either CD33+/CD14+, CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method are therefore particularly well suited for immunotherapeutic protocols.
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PMID:Expansion of dendritic cells derived from human CD34+ cells in static and continuous perfusion cultures. 960 35

The antigen-presenting capacity of dendritic cells (DCs) makes them attractive potential cellular adjuvants for vaccination strategies. Currently, most in vitro culture systems for the production of these DCs include serum. However, this is undesirable because serum contains growth factors that vary between individuals and could affect DC development. Unless the patient's own serum is used, foreign antigens and the risk of infection will detract from the usefulness of these cells in clinical strategies. In this study we investigated the production of DCs from CD34+ progenitor cells of cancer patients or normal donors under serum-free conditions. We have established a model system for the investigation of DC development and maturation. Dendritic cells that developed from myeloid precursors accumulated after 2 weeks in an intermediate CD1a , CD80-, CD83-, CD86- stage. Intermediate DCs adhered to plastic surfaces, expressed Birbeck granules, and were negative for CD2 and CD14. In the presence of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha, interleukin-4 promoted the development of these stages. Spontaneous maturation of intermediate DCs into fully activated DCs expressing CD83 and costimulatory molecules occurred asynchronously over the ensuing 2 to 3 weeks. This maturation involved increased expression of CD80, CD83, CD86, CMRF-44, HLA-A, -B, -C, and -DR as well as downregulation of CD1a and CD11b. Activated DCs are characterized by the lack of adherence to plastic surfaces and the absence of Birbeck granules. By day 28, these cells were nonphagocytic, potent antigen-presenting cells with an irreversible phenotype. This serum-free system offers advantages in that the process of differentiation and maturation of committed DCs is extended over a period of more than 28 days, allowing investigators to study the effects of individual cytokines or other supplements during distinct phases of DC development in a defined environment.
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PMID:A serum-free culture model for studying the differentiation of human dendritic cells from adult CD34+ progenitor cells. 962 Feb 82

The CD14-dependent and -independent dendritic cell (DC) pathways are instituted simultaneously when CD34(+) progenitor cells are treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor (TNF) +/- stem cell factor (SCF) (GTS). If TNF activity is neutralized within 48 hours of cytokine exposure, DC development is halted and myelogranulocytic hematopoiesis takes place. In this study, we show that disruption of TNF activity at a later time point produced a distinct alteration within the DC system. Instead of downregulating DC development, treatment of GTS cultures with antibodies to TNF (anti-TNF) on day 3 provoked the selective expansion of the CD14-dependent (monocyte) DC pathway from progenitor cell populations lacking CD14 and CD1a. After an initial decrease in proliferation, anti-TNF produced a rebound in cell growth that yielded intermediate myeloid progenitors exhibiting CD14-dependent DC differentiation potential and CD14(+)CD1a+ DC precursors. Cultures enriched in CD14-dependent DCs were more potent stimulators of a mixed leukocyte reaction, compared with control GTS cultures containing both types of DCs. The intermediate progenitors expanded in the presence of anti-TNF were CD115(+)CD33(+)DR+, long-lived, and displayed clonogenic potential in methylcellulose. When exposed to the appropriate cytokine combinations, these cells yielded granulocytes, monocytes, and CD14-dependent DCs. Antigen-presenting function was acquired only when DC maturation was induced from these myelodendritic progenitors with GM-CSF + interleukin-4 or GTS. These studies show a novel mechanism by which TNF regulates the DC system, as well as providing a strategy for the amplification of the CD14-dependent DC pathway from immature progenitors. Although TNF is required to ensure the institution of DC hematopoiesis from CD34(+) progenitor cells, its activity on a later progenitor appears to limit the development of CD14-dependent DCs.
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PMID:Neutralization of tumor necrosis factor activity shortly after the onset of dendritic cell hematopoiesis reveals a novel mechanism for the selective expansion of the CD14-dependent dendritic cell pathway. 968 Mar 40

The goal of the present paper was to define the immunophenotype of bone marrow mast cells (BMMC) from healthy controls and patients with hematologic malignancies (HM) based on the use of multiple stainings with monoclonal antibodies analyzed by flow cytometry. Our results show that BMMC from both groups of individuals display a similar but heterogeneous immunophenotype. The overall numbers of BMMC are higher in the HM group of individuals (p = 0.08). Three patterns of antigen expression were detected: (1) markers constantly positive in all cases analyzed (CD9, CD29, CD33, CD43, CD44, CD49d, CD49e, CD51, CD71, CD117, and Fc(epsilon)RI), (2) antigens that were constantly negative (CD1a, CD2, CD3, CD5, CD6, CD11a, CD14, CD15, CD16, CD19, CD20, CD21, CD23, CD25, CD30, CD34, CD38, CD41a, CD42b, CD65, CD66b, HLA-DR, and CD138), and (3) markers that were positive in a variable proportion of cases--CD11b (50%), CD11c (77%), CD13 (40%), CD18 (20%), CD22 (68%), CD35 (27%), CD40 (67%), CD54 (88%) and CD61 (40%). In addition, BMMC from all cases explored were CD45+, and this antigen was expressed at an intensity similar to that of mature granulocytes. In summary, our results show that BMMC from both healthy controls and HM patients display a relatively heterogeneous immunophenotype. Interestingly, we have observed clear differences between the immunophenotype of BMMC and MC from other tissues. This could be due either to the heterogeneity of human MC according to their tissue localization or to the sensitivity of the method used for antigen detection.
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PMID:Immunophenotypic characterization of human bone marrow mast cells. A flow cytometric study of normal and pathological bone marrow samples. 969 44


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