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 (DC) present Ag to naive T cells and are therefore pivotal in shaping immune responses. DC may either immunize or tolerize T cells. Humans with pancreatic islet autoimmunity at high risk for insulin-dependent diabetes mellitus (IDDM) present the opportunity to investigate DC in autoimmune disease. We compared DC phenotype and function in 12 euglycemic, asymptomatic IDDM relatives with islet autoimmunity and controls matched for age, sex, and MHC class II alleles. DC were generated from adherent peripheral blood cells by culture with granulocyte/macrophage-CSF and IL-4. The yield of DC was significantly lower in IDDM relatives than in controls. While the DC phenotype, HLA-DR+CD14-, was expressed by > or =90% of the cells generated from relatives and controls, the proportion of cells that expressed CD1a and the costimulator molecules CD80 (B7-1) and CD86 (B7-2) was significantly lower in IDDM relatives. In addition, B7-1 and B7-2 expression per cell was significantly lower in IDDM relatives. These phenotypic changes were accompanied by reduced stimulation of autologous CD4 cells by DC from IDDM relatives. Similar findings were obtained in three recently diagnosed IDDM patients. These findings indicate that impairment of DC phenotype and function is a marker of islet autoimmunity and are consistent with a role for impaired DC function in the pathogenesis of autoimmune disease.
 ...
PMID:Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes. 972 65

Dendritic cells (DC), the most potent antigen-presenting cells found to date, can be generated from the adherent fraction of peripheral blood mononuclear cells (PBMC) by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. When interferon gamma (IFN-gamma) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MHC II (MHC-DR), CD11a and CD54 were increased. T cell proliferation analysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-gamma only induced weak responses in both activated and naive allogenic CD4(+) and CD8(+) T cells when compared to the reaction elicited by DC cultured without IFN-gamma. Furthermore, the DC derived from cultures with IFN-gamma, loaded with an immunogenic peptide derived from the HER2/neu protein [HER2 (9466)], only induced low levels of TNF release and weak proliferative responses in a specific cytotoxic CD8(+) T lymphocyte clone. Therefore, our results indicate that IFN-gamma negatively influences the differentiation and function of monocyte-derived DC by affecting the expression of surface molecules involved in their antigen-presenting function. This supports the general hypothesis that there exists a feedback immune regulatory mechanism between T cells and monocytes/DC.
 ...
PMID:Interferon gamma impairs the ability of monocyte-derived dendritic cells to present tumour-specific and allo-specific antigens and reduces their expression of CD1A, CD80 AND CD4. 981 27

The escape of malignant cells from the immune response against the tumor may result from a defective differentiation or function of professional antigen-presenting cells (APC), ie, dendritic cells (DC). To test this hypothesis, the effect of human renal cell carcinoma cell lines (RCC) on the development of DC from CD34(+) progenitors was investigated in vitro. RCC cell lines were found to release soluble factors that inhibit the differentiation of CD34(+) cells into DC and trigger their commitment towards monocytic cells (CD14(+)CD64(+)CD1a-CD86(-)CD80(-)HLA-D Rlow) with a potent phagocytic capacity but lacking APC function. RCC CM were found to act on the two distinct subpopulations emerging in the culture at day 6 ([CD14(+)CD1a-] and [CD14(-)CD1a+]) by inhibiting the differentiation into DC of [CD14(+)CD1a-] precursors and blocking the acquisition of APC function of the [CD14(-)CD1a+] derived DC. Interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) were found to be responsible for this phenomenon: antibodies against IL-6 and M-CSF abrogated the inhibitory effects of RCC CM; and recombinant IL-6 and/or M-CSF inhibited the differentiation of DC similarly to RCC CM. The inhibition of DC differentiation by RCC CM was preceeded by an induction of M-CSF receptor (M-CSFR; CD115) and a loss of granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR; CD116) expression at the surface of CD34(+) cells, two phenomenon reversed by anti-IL-6/IL-6R and anti-M-CSF antibodies, respectively. Finally, a panel of tumor cell lines producing IL-6 and M-CSF induced similar effects. Taken together, the results suggest that the inhibition of DC development could represent a frequent mechanism by which tumor cells will escape immune recognition.
 ...
PMID:Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. 984 45

Since dendritic cells (DCs) are the most professional antigen-presenting cells, (Schuler et al., 1997), increasing interest in their use in clinical approaches has been observed. (Nestle et al., 1998; Murphy G. et al., 1996). We have developed an ex vivo standardized process for the generation of dendritic-like cells (MAC-DCs) from human blood circulating monocytes. Human monocytes can differentiate into very different functional cells according to the conditions of culture, media and cytokines used. In the present study, we demonstrate that both pure monocytes and mononuclear cells differentiate into DCs when they are grown in defined medium AIM-V in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus IL13 and in approved biocompatible non-adherent bags. Quality and functional controls of the immature DCs obtained rely on bacterial sterility, viability, morphology and recovery. The MAC-DCs also present an immature DC phenotype with a low expression of CD14 and CD64, and high expression of MHC-I, MHC-II and CD40. They also express B7 costimulatory molecules (CD80, CD86), CD83, and CD1a molecules. They induce strong allogenic T-cell proliferation (mixed lymphocyte reaction as well as proliferation of autologous memory T lymphocytes when incubated in the presence of recall antigens (tuberculosis, Candida albicans, and tetanus toxoid). They also show an increase in phagocytic uptake of yeast, tumour cells and debris. The global closed system which, under reproducible good medical practice (GMP) conditions, enables the production of dendritic cells of clinical quality, has been optimized ("Vac Cell Processor"). It contains all bags, connections, media, reagents, washing solutions, control antibodies, standard operating procedures, data management, traceability and help in the form of dedicated software.
 ...
PMID:Monocyte-derived dendritic cells: development of a cellular processor for clinical applications. 985 16

Ultraviolet (UV) irradiation of the skin induces complex local and systemic immunomodulatory reactions. The biological effects of UV irradiation on human skin derived afferent lymph however are unknown. The aim of this study was to examine the effects of a single combined UV-A and UV-B irradiation with 1 minimal erythema dose (MED) on human skin derived lymph in vivo. After cannulation of a superficial lymph vessel on the lower leg, lymph flow and cell output per hour were determined before and for 6 days after UV irradiation of the lymph draining skin area in 5 volunteers. Furthermore, expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells and cytokine levels (IL-1alpha, IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-13, TNF-alpha and IFN-gamma) in the afferent lymph were analyzed by cytofluorometry and ELISA. After UV irradiation a small initial enhancement in the daily lymph flow per hour was noticed in correlation with the slight erythematous skin reaction. Following resolution of the skin reaction, a delayed increase in cell output in correlation with an additional peak in the lymph flow was found between the 4th and 6th day after UV irradiation. However, no changes in the expression of CD1a, CD4, CD8, CD28, CD54, CD80, CD86 and HLA-DR on migrating lymph cells were detectable. Interestingly, in parallel to the increased lymph flow and cell output, only elevated IL-8 protein levels were reproducibly detected in the afferent lymph after UV irradiation. Furthermore, using immunohistochemistry positive staining for IL-8 was found on migrating mononuclear lymph cells. In conclusion, our data demonstrate that a single UV irradiation of the skin with 1 minimal erythema dose leads to a delayed enhancement of lymph flow, number of migrating lymph cells and cytokine levels of IL-8. Moreover, we provide evidence that migrating lymph cells, besides resident epidermal and dermal cells, may contribute to the detected levels of IL-8 in the afferent lymph.
 ...
PMID:Effects of UV irradiation with one minimal erythema dose on human afferent skin lymph in vivo. 985 39

We previously showed that in chronic myeloid leukaemia (CML), it is possible to induce costimulatory molecules, CD80/CD86, on leukaemia cells by culturing adherent peripheral blood mononuclear cells from these patients with IL-4 and GM-CSF. In addition to the expression of CD80/CD86 molecules, some of the leukaemia cells also expressed the dendritic cell marker, CD1a. When these leukaemia cells were used in mixed lymphocyte leukaemia reactions, they mediated autologous T cell proliferation not seen when fresh leukaemia cells were used as the stimulator cells. In this study, we showed that reinfusion of these immunogenic leukaemia cells to the autologous hosts resulted in priming in vivo of T cells so that they could respond to subsequent rechallenge in vitro with fresh autologous leukaemia cells. Although cytotoxic T cells against leukaemia cells were not demonstrated, these T cells could proliferate and produce interferon-y when cocultured in vitro with the leukaemia cells. Our findings therefore provide further evidence for the immunogenicity of these cultured leukaemia cells in CML.
 ...
PMID:In vitro cytokine-primed leukaemia cells induce in vivo T cell responsiveness in chronic myeloid leukaemia. 989 22

Dendritic cells (DCs) are pivotal for antigen presentation, T-cell priming and B-cell functions. Few studies have been carried out on DCs in human diseases, partly because the current procedures used for DC preparation include elaborate negative selection with monoclonal antibodies (MoAb) and prolonged culture in cytokine-enriched milieu, which may influence DC functions. Using physical density and their adherent properties, DCs were prepared from the blood of healthy subjects. Approximately 2% of human blood mononuclear cells (MNC) were shown to consist of DCs, yielding DCs of 80-90% purity. They expressed markers related to DCs (CD1a, CD11c, CD32 and CD83), costimulatory molecules (CD40, CD80, CD86), human leucocyte antigen (HLA) class I and II molecules and inducible nitric oxide (NO) synthase (NOS2), and lacked lymphocyte and monocyte markers (CD3, CD19, CD20, CD56 and CD14). Compared with blood MNC and T cells, DCs showed a high level of spontaneous proliferation and nitric oxide production, as well as strong proliferative responses in mixed leucocyte reactions. Enzyme-linked immunospot (ELISPOT) assays revealed higher levels of interleukin (IL)-4-, IL-10- and interferon-gamma (IFN-gamma)-secreting cells among DCs than among MNC or T cells obtained from the same blood specimens, while levels of tumour necrosis factor-alpha (TNF-alpha)- and IL-6-secreting cells did not differ. The results demonstrate that the method used is fast, effective and competitively priced, and should be useful for studies of DCs in disease states.
 ...
PMID:Phenotypic and functional properties of dendritic cells isolated from human peripheral blood in comparison with mononuclear cells and T cells. 1007 22

Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease after CB transplantation. Here, CBDC were identified as a HLA-DR+ cell population, lacking the CD3, CD11b, CD14, CD16, CD19, CD34, CD56, and glycophorin A lineage markers (lin). This lin-/HLA-DR+ population represented 0.3% +/- 0.1% (mean +/- SD; range, 0.1% to 0. 6%; n = 15) of CB mononuclear cells, and CB contained 5.4 +/- 3.2 x 10(3) CBDC/mL (1.8 to 13.0 x 10(3); n = 15). CBDC expressed CD4, CD11a, CD18, CD45RA, CD50, CD54, and CD123, but showed no expression of CD1a, CD11c, CD33, CD40, CD45R0, CD80, CD83, and CD86 and only limited expression of CD58, CD102, and CD116. Despite this immature phenotype, immunomagnetically lin--enriched CBDC were potent stimulators of allogeneic CB T cells. As few as 266 +/- 107 (193 to 530; n = 10) lin-/HLA-DR+ CBDC stimulated a significant response. However, CBDC failed to take up protein or peptide antigens. Thus, in CB there is a prevalence of a DC subpopulation, resembling the CD11c- DC identified in tonsils, the so-called plasmacytoid T cells, which may exert a function distinct from the CD11c+ DC subpopulation.
 ...
PMID:Identification of cord blood dendritic cells as an immature CD11c- population. 1009 Sep 40

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) specialized to internalize, process, and present antigen. They have the capacity to stimulate the primary immune response of resting T-cells. We generated DCs from the adherent cell fraction of peripheral blood, as well as from purified CD34+ cells from CML patients. Characterizing DCs from ten CML patients by flow cytometry, we found that these cells are highly positive for HLA-DR, CD1a, CD23, and CD80 and negative for CD14, CD15, and CD16. The yield of DCs ranged from 19.5 to 68%. In addition, we used a functional test of FITC-dextran uptake to verify that early DCs take up large particles (0.5-3 microm) by macropinocytosis while monocytes do not. FITC-dextran uptake was detected by flow cytometry, showing that DCs had accumulated these fluorescent particles. Electron-microscopic analysis showed no major morphological differences between normal and CML-derived DCs. Furthermore, cultured DCs were isolated by FAC sorting for CD1a and HLA-DR expression. In these highly purified cells the Ph chromosome was detected by interphase fluorescence in situ hybridization (FISH) and by fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION); 30-85% of DCs generated were Ph-chromosome positive. It might therefore be possible not only to prime T-cells with bcr/abl-specific synthetic peptides, but also to stimulate T-cells directly with Ph-positive DCs. Use of DCs might serve as a novel therapeutic approach in CML patients, due to their ability to induce highly specific T-cell responses in an autologous system.
 ...
PMID:Generation of dendritic cells from patients with chronic myelogenous leukemia. 1034 49

We studied the effects of interferon-beta (IFN-beta) on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells (PBMC) from a total of 30 healthy volunteers in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found that the addition of IFN-beta at the initiation of the culture did not modify DC morphology but caused a reproducible and statistically significant upregulation of HLA-DR, CD86, and CD80 surface expression. CD1a expression was significantly reduced, and CD40 expression was unchanged. We then determined the influence of IFN-beta on the production of cytokines by DC. DC differentiated in the presence of IFN-beta secreted significantly less IL-12 (p40 and p70) both spontaneously and on activation by fibroblasts transfected with the CD40L gene. This effect of IFN-beta was dose dependent and selective, as it was not observed for IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha). As a consequence, DC differentiated in the presence of IFN-beta induced significantly less IFN-gamma secretion by alloreactive T cells, whereas they were more efficient than control DC in eliciting IL-5 secretion. We conclude that the direct action of IFN-beta on DC causes inhibition of their ability to secrete IL-12 in response to CD40 ligation and to elicit Th1 type responses.
 ...
PMID:IFN-beta interferes with the differentiation of dendritic cells from peripheral blood mononuclear cells: selective inhibition of CD40-dependent interleukin-12 secretion. 1038 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>