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)

The ability of CD34+ leukemic cells to differentiate to dendritic cells (DCs) was investigated in 18 acute myeloid leukemia (AML) and 4 lymphoid leukemia (ALL) patients. The generation of DCs was determined by the expression of DC-associated CD1a or CD83 (more than 30%) with costimulatory molecules, by CD80 antigens (>20%), and by the exhibition of allostimulatory activity. In the AML patients, allostimulatory mature DCs were generated from 3 of 9 M0 or M1, 2 of 5 M2,2 of 4 M4 or M5, and 3 of 4 ALL (L2) cases. In total, DCs were more efficiently induced from cases expressing over 75% of CD34+ among whole bone marrow mononuclear cells (8 of 12), compared with those under 75% (2 of 10; P < .05). B-cell (CD19), natural killer (NK)-cell (CD56), or T-cell (CD7) lineage markers, which were aberrantly expressed on the blasts, were rarely found on leukemic DCs at the end of the culture period, and myeloid (CD13, CD33), not lymphoid (CD10), markers were shown on ALL-derived DCs. In Philadelphia chromosome-positive ALL or AML patients with t (8;21), DCs were confirmed to be of leukemic origin by fluorescence in situ hybridization analysis.
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PMID:The generation of immunocompetent dendritic cells from CD34+ acute myeloid or lymphoid leukemia cells. 1184 92

The objective of this study was to investigate CD163+ macrophages in the synovial membrane of patients with spondyloarthropathy (SpA). Immunohistochemistry was performed on synovium of 17 SpA and 18 rheumatoid arthritis (RA) patients, on colonic biopsies of 16 SpA patients and ten healthy controls, and on paired synovial biopsies of eight SpA patients, before and after anti-TNFalpha therapy. Phenotype and cytokine production were analysed by flow cytometry. CD163+ macrophages were increased in the synovial lining and sublining in SpA versus RA, as well as in colonic lamina propria in SpA versus controls. The number of CD163+ macrophages in the synovial sublining correlated with C-reactive protein levels and erythrocyte sedimentation rate. Paralleling the increase of CD163, HLA-DR was increased in the synovial lining and sublining of SpA. In contrast, the co-stimulatory molecules CD80 and CD86 and the dendritic cell markers CD1a and CD83 were scarce in SpA synovium. Flow cytometry indicated that CD163+ macrophages expressed high levels of HLA-DR and could produce in vitro tumour necrosis factor alpha (TNFalpha) but not interleukin-10 (IL-10). Finally, anti-TNFalpha therapy in vivo induced a decrease of CD163+ macrophages in the synovial lining and sublining. In conclusion, macrophages expressing the scavenger receptor CD163 are increased in synovium and in colonic mucosa in SpA, highlighting the relationship between joint and gut in this disease. The correlation with inflammatory parameters, the expression of HLA-DR, the production of TNFalpha but not IL-10, and the reduction by anti-TNFalpha therapy support a role for CD163+ macrophages in the synovial inflammation in SpA.
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PMID:Macrophages expressing the scavenger receptor CD163: a link between immune alterations of the gut and synovial inflammation in spondyloarthropathy. 1185 99

The object of this study is to explore a culture method to generate a large number of functional and mature dendritic cells (DC) from human CD34+ hematopoietic progenitor cells. In the present study, we used a two-step method combined with calcium ionophore to induce DC from cord blood (CB) or normal human bone marrow (BM) CD34+ progenitor cells. The two-step method consists of 10 days of first step culture for the expansion and proliferation of CD34+ hematopoietic progenitor cells in the presence of SCF, IL-3, IL-6, G-CSF, and 7--11 days of second step culture for the induction of DC in the presence of GM-CSF, IL-4 and TNF-alpha. By the two-step culture, total nucleated cells were increased 208+/-66 (+/-SD, n=13), or 94+/-29 (n=5)-fold in the culture of CB or BM cells, respectively, compared with the number of CD34+ cells at the time of starting culture. Out of the total nucleated cells, 23 +/-10.4% of cells in CB cell culture and 25 +/-5% of cells in the BM cell culture acquired DC characteristic phenotypes, which were marked expressions of CD1a, HLA-DR, co-stimulatory molecules such as CD80, CD40, and adhesion molecule such as CD58. In allogeneic mixed leukocyte reaction (MLR), two-step cultured cells showed potent allo-stimulatory capacity. With this two-step culture, the absolute number of CD1a+ cells that co-expressed HLA-DR, CD80, CD40 and CD58 was enhanced approximately 3 times in CB cell culture and 1.9 times in BM cell culture, compared with the commonly used one-step culture method for the generation of DC from CD34+ cells using SCF, GM-CSF and TNF-alpha. However, on these DC generated in the two-step culture, the expressions of co-stimulatory molecule CD86 and mature DC marker CD83 were not sufficient. By the treatment of two-step cultured cells with calcium ionophore agent (A23187), the expression of co-stimulatory molecules such as CD86 and CD80 (especially CD86) was up-regulated. Besides, the expression of mature DC marker CD83 was remarkably induced by treatment with A23187 for a short duration (24 h). Consistent with the up-regulation of surface molecules CD86, CD80 and CD83, the two-step cultured cells treated with A23187 also showed a stronger allo-stimulatory capacity compared with the cells without A23187 treatment. In conclusion, the present study demonstrated that the two-step culture method effectively improved the yield of CD1a+ DC generated from CD34+ cells, and the phenotypes and functions of these CD1a+ DC could be enhanced efficiently by treatment with a calcium ionophore agent.
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PMID:Generation of functional and mature dendritic cells from cord blood and bone marrow CD34+ cells by two-step culture combined with calcium ionophore treatment. 1186 Oct 65

The skin is a unique organ that contains two different subsets of dendritic cells, i.e., Langerhans cells and dermal dendritic cells. Our hypothesis is that cutaneous fibroblasts may affect the development of these dendritic cells. We cocultured cord blood CD34+ hematopoietic progenitor cells with several human cutaneous fibroblast cell lines without any exogenous cytokines for 3 wk. In this culture, hematopoietic progenitor cells increased in number from 20.1 +/- 2.4 times, and produced aggregates of cells with dendritic processes. They were composed of 54.9 +/- 3.2% HLA-DR+ CD14+ CD1a-- cells and 13.8 +/- 3.6% HLA-DR+ CD1a+ cells, which also expressed CD11b and CD11c. There were significant numbers of factor XIIIa+ cells in the culture, whereas no Lag+ or E-cadherin+ cells were detected, and they were potent stimulators in allogeneic T cell activation. There was a significant difference in the ability to induce CD1a+ cells among different human cutaneous fibroblast cell lines. These CD1a+ cells lacked the expression of CD80, CD86, or CD83. In addition, half of them still expressed CD14. When these dendritic cells were cultured with tumor necrosis factor-alpha, however, they became mature dendritic cells with augmented expression of CD86 and CD83 and with increased allogeneic T cell stimulation. The subsequent experiment using a dividing chamber, enzyme-linked immunosorbent assay for granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, and the blocking studies with antibodies for these cytokines suggested that both the presence of direct contact between hematopoietic progenitor cells and human cutaneous fibroblast cell lines and macrophage colony-stimulating factor produced by human cutaneous fibroblast cell lines are required for their maximum growth and differentiation into CD1a+ dendritic cells, whereas macrophage colony-stimulating factor was solely responsible for their differentiation. These data suggest that cutaneous fibroblasts support the differentiation of dermal dendritic cells in addition to that of monocytes from hematopoietic progenitor cells by their direct contact with hematopoietic progenitor cells and by their macrophage colony-stimulating factor production.
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PMID:Cord blood CD34+ cells differentiate into dermal dendritic cells in co-culture with cutaneous fibroblasts or stromal cells. 1187 84

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BP) are environmental carcinogens exhibiting potent immunosuppressive properties. To determine the cellular bases of this immunotoxicity, we have studied the effects of PAHs on differentiation, maturation, and function of monocyte-derived dendritic cells (DC). Exposure to BP during monocyte differentiation into DC upon the action of GM-CSF and IL-4 markedly inhibited the up-regulation of markers found in DC such as CD1a, CD80, and CD40, without altering cell viability. Besides BP, PAHs such as dimethylbenz(a)anthracene and benzanthracene also strongly altered CD1a levels. Moreover, DC generated in the presence of BP displayed decreased endocytic activity. Features of LPS-mediated maturation of DC, such as CD83 up-regulation and IL-12 secretion, were also impaired in response to BP treatment. BP-exposed DC poorly stimulated T cell proliferation in mixed leukocyte reactions compared with their untreated counterparts. In contrast to BP, the halogenated arylhydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin, which shares some features with PAHs, including interaction with the arylhydrocarbon receptor, failed to phenotypically alter differentiation of monocytes into DC, suggesting that binding to the arylhydrocarbon receptor cannot mimic PAH effects on DC. Overall, these data demonstrate that exposure to PAHs inhibits in vitro functional differentiation and maturation of blood monocyte-derived DC. Such an effect may contribute to the immunotoxicity of these environmental contaminants due to the major role that DC play as potent APC in the development of the immune response.
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PMID:Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells. 1188 29

Sarcoidosis, a chronic granulomatous disease of unknown etiology, is treated with immune suppressive drugs such as corticosteroids. Sarcoidosis patients have been reported to benefit clinically from treatment with thalidomide. We administered thalidomide for 16 weeks to eight patients with chronic skin sarcoidosis and evaluated the drug's effects before and with treatment. After thalidomide treatment, all skin biopsies showed decreases in granuloma size and reduction in epidermal thickness. We also observed extensive T cell recruitment into the granulomas, the appearance of multinucleated giant cells, and increased numbers of dermal Langerhans cells (CD1a(+)) and mature dendritic cells (CD83(+) or DC-LAMP(+)). Plasma IL-12 levels increased and remained elevated during the treatment period. We noted increased HLA-DR expression on peripheral blood lymphocytes and a corresponding drop in the naive T cell marker CD45RA. Our data suggest that thalidomide treatment of sarcoidosis results in granuloma differentiation to a Th1-type cellular immune response usually associated with protective immunity to tuberculosis and tuberculoid leprosy.
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PMID:Thalidomide induces granuloma differentiation in sarcoid skin lesions associated with disease improvement. 1189 Jul 9

The American cutaneous forms of leishmaniasis include immune-responder individuals with localised cutaneous leishmaniasis (LCL) and non-responder individuals with diffuse cutaneous leishmaniasis (DCL). Patients with intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity due to the length of their illness, atypical forms and areas of compromise. In the present study, we evaluated the expression of the leukocyte antigens (CD4, CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18) using an immunocytochemical procedure. ICL results were compared with the information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T cells in ICL were similar to those of LCL lesions, but significantly different (P < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells, whereas ICL lesions have the highest number of CD69+ T cells, but about one-third of these cells expressed CLA. This suggests that the granuloma of ICL patients contains many activated T cells that are unprimed to cutaneous-launched antigens, thus contributing to an aberrant immune response. In contrast, DCL granulomas presented the lowest numbers of activated CD69+ and CLA+ cells, associated with the characteristic tolerogenic state of these patients. The immunolocalisation of cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two, and different from the prevalent Th1 and Th2 responses associated with LCL and DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05) in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in ICL epidermis. The diminished participation of epidermal Langerhans cells, causing a defective signalling by the epidermis, in ICL lesions may account for the tissue-damaging state observed in these patients.
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PMID:Intermediate or chronic cutaneous leishmaniasis: leukocyte immunophenotypes and cytokine characterisation of the lesion. 1195 26

Human immunodeficiency virus (HIV)-1 Nef protein is an essential modulator of AIDS pathogenesis and we have previously demonstrated that rNef enters uninfected human monocytes and induces T cells bystander activation, up-regulating IL-15 production. Since dendritic cells (DCs) play a central role in HIV-1 primary infection we investigated whether rNef affects DCs phenotypic and functional maturation in order to define its role in the immunopathogenesis of AIDS. We found that rNef up-regulates the expression on immature DCs of surface molecules known to be critical for their APC function. These molecules include CD1a, HLA-DR, CD40, CD83, CXCR4, and to a lower extent CD80 and CD86. On the other hand, rNef down-regulates surface expression of HLA-ABC and mannose receptor. The functional consequence of rNef treatment of immature DCs is a decrease in their endocytic and phagocytic activities and an increase in cytokine (IL-1beta, IL-12, IL-15, TNF-alpha) and chemokine (MIP-1alpha, MIP-1beta, IL-8) production as well as in their stimulatory capacity. These results indicate that rNef induces a coordinate series of phenotypic and functional changes promoting DC differentiation and making them more competent APCs. Indeed, Nef induces CD4(+) T cell bystander activation by a novel mechanism involving DCs, thus promoting virus dissemination.
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PMID:HIV-1 Nef induces dendritic cell differentiation: a possible mechanism of uninfected CD4(+) T cell activation. 1196 93

It remains to be clarified whether dendritic cells (DC) reach the rheumatoid arthritis (RA) synovium, considered an ectopic lymphoid organ, as mature cells or undergo local maturation. We characterized by immunohistochemistry the DC subsets and used tonsils as a control. Immature and mature DC were defined by CD1a and DC-lysosome-associated membrane protein/CD83 expression, respectively. Immature DC were mainly detected in the lining layer in RA synovium. Mature DC were exclusively detected in the lymphocytic infiltrates. The DC-lysosome-associated membrane protein/CD1a ratio was 1.1 in RA synovium and 5.3 in tonsils, suggesting the relative accumulation of immature DC in RA synovium. We then focused on the expression of CCL20/CCR6 and CCL19/CCR7, CCL21/CCR7 chemokine/receptor complex, which control immature and mature DC migration respectively. A close association was observed between CCL20-producing cells and CD1a(+) cells, suggesting the contribution of CCL20 to CCR6(+) cell homing. Conversely, CCL21 and CCL19 expression was only detected in perivascular infiltrates. The association among CCL19/21-producing cells, CCR7 expression, and mature DC accumulation is in line with the roles of these chemokines in mature CCR7(+) DC homing to lymphocytic infiltrates. The role of DC in disease initiation and perpetuation makes chemokines involved in DC migration a potential therapeutic target.
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PMID:Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium. 1199 92

CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) superfamily and is expressed primarily on the activated CD4( )T lymphocytes. The CD40 molecule, the cognate receptor of CD40L presents on many immunocytes such as B lymphocytes, dendritic cells (DCs) as well as on some neoplastic cells. Triggering of CD40 through CD40L plays a central role in the initiation and regulation of the human immune response. In order to further investigate the possible biological roles of CD40 signaling triggered by CD40L, we subcloned the DNA fragment encoding the extracellular region of human CD40L into the pSK plasmid. After being sequenced, the target fragment was introduced into the pPICZalphaA plasmid to construct the pPICZalphaA-sCD40L expressing vector which was then transduced into Pichia pastoris GS115 cells by electroporation. The tansformant expressed sCD40L in culture supernatants with a maximum yield of about 35 mg/L. Furthermore, we found that the recombinant human soluble CD40 ligand (rhsCD40L) could effectively induced human peripheral blood monocytes(PBMCs) in vitro in the absence of TNFalpha into dendritic cells (DCs) with the typical morphology and special surface markers of dendritic cells including CD1a, CD80, CD83, and HLA-DR etc. To our surprise, the rhsCD40L also could inhibit directly in vitro proliferation of the CD40-positive multiple myeloma cell line XG-2 and the B lymphoma cell line Daudi significantly at an optimal concentration from 2.5 to 15.0 mg/L, while CD40 negative ovarian carcinoma cell lines, SKB and SKR, were not effected by either high or low concentration of rhsCD40L. Moreover, rhsCD40L had the same effects as CD40L-transfected cell in inducing XG2 cell apoptosis. Our results demonstrated that functional human soluble CD40L could be successfully expressed in the Pichia pastoris system and that the recombinant human soluble CD40L might be a potential immune adjuvant and a new powerful molecule for tumor bio-therapy.
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PMID:Expression of Human Soluble CD40 Ligand in Pichia pastoris and Its Effects on Dendritic Cells and Malignant B Cells. 1205 65


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