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)

Myeloid dendritic cells (DCs) are conventionally generated by culturing human peripheral blood monocytes in the presence of GM-CSF and IL-4. Here we report that IL-4 alone, in the absence of detectable endogenous GM-CSF, transforms human peripheral blood monocytes to a CD1a(dim) DC subset that could be matured to CD83(+) DCs. Absence of endogenous GM-CSF in IL-4-DC was demonstrated by RT-PCR and flow cytometry. With the exception of CD1a expression, surface marker, morphology and phagocytic activity of these DCs (IL-4-DC) were similar to myeloid DCs (GM-IL-4-DC) conventionally generated in the presence of GM-CSF and IL-4. Conventional GM-IL-4-DC produced less IL-12 compared with IL-4-DC after stimulation with anti-CD40 monoclonal antibody, or LPS plus IFN-gamma, although the difference was more prominent when LPS plus IFN-gamma was used as the stimulus. The GM-IL-4-DC also induced less frequent IFN-gamma(+) T cells in a mixed leukocyte reaction (MLR) than that of IL-4-DC. Yields of IL-4-DCs were marginally lower than that of GM-IL-4-DCs. Our data indicate that peripheral blood monocytes can be transformed to CD1a-deficient myeloid DCs solely by IL-4, and these IL-4-DCs are likely to induce a stronger Th1 response than conventional GM-IL-4-DCs.
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PMID:IL-4 alone without the involvement of GM-CSF transforms human peripheral blood monocytes to a CD1a(dim), CD83(+) myeloid dendritic cell subset. 1521 52

Differentiation of tissue monocytes into DCs is a critical phase in the development of a competent immune system. We show that in a nicotinic environment, while human monocytes differentiate into DCs (henceforth called nicDCs) with a typical morphology, they display unique phenotype and cytokine profile that adversely affect their function. Despite an increased capacity for receptor-dependent antigen uptake, nicDCs do not express CD1a and fail to fully up-regulate MHCs, molecules essential for their antigen-presenting function. Additionally, in response to bacterial antigen LPS, maturing nicDCs hardly express the chemotactic cytokine receptor 7 required for their entry into lymphatic vessels. Furthermore, in parallel with their differential expression of costimulatory molecules CD80 and CD86 and lack of IL-12, nicDCs display profoundly reduced Th1 promoting capacity. These findings thus indicate that nicotine impedes the development of cell-mediated immunity by skewing DC differentiation. These effects of nicotinic environment on DC differentiation may contribute to the increased risks of respiratory tract infection and various cancers in smokers.
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PMID:Nicotinic environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs). 1532 97

Acute and chronic Plasmodium falciparum malaria are accompanied by severe immunodepression possibly related to subversion of dendritic cells (DC) functionality. Phagocytosed hemozoin (malarial pigment) was shown to inhibit monocyte functions related to immunity. Hemozoin-loaded monocytes, frequently found in circulation and adherent to endothelia in malaria, may interfere with DC development and play a role in immunodepression. Hemozoin-loaded and unloaded human monocytes were differentiated in vitro to immature DC (iDC) by treatment with GM-CSF and IL-4, and to mature DC (mDC) by LPS challenge. In a second setting, hemozoin was fed to iDC further cultured to give mDC. In both settings, cells ingested large amounts of hemozoin undegraded during DC maturation. Hemozoin-fed monocytes did not apoptose but their differentiation and maturation to DC was severely impaired as shown by blunted expression of MHC class II and costimulatory molecules CD83, CD80, CD54, CD40, CD1a, and lower levels of CD83-specific mRNA in hemozoin-loaded iDC and mDC compared with unfed or latex-loaded DC. Further studies indicated activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in hemozoin-loaded iDC and mDC, associated with increased expression of PPAR-gamma mRNA, without apparent involvement of NF-kappaB. Moreover, expression of PPAR-gamma was induced and up-regulation of CD83 was inhibited by supplementing iDC and mDC with plausible concentrations of 15(S)-hydroxyeicosatetraenoic acid, a PPAR-gamma ligand abundantly produced by hemozoin via heme-catalyzed lipoperoxidation.
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PMID:Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptor-gamma-mediated effect. 1535 56

Myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. MDS patients have a defective immune response manifested by increased susceptibility to bacterial infections, autoimmune phenomena, and high incidence of lymphoid malignancies. Presently, we investigated the phenotype and function of monocyte-derived dendritic cells (MoDC) in 23 MDS patients and 15 controls at different stages of differentiation using the maturation stimuli tumor necrosis factor-alpha (TNF-alpha) and LPS. Monocytes from MDS patients showed low potential to differentiate into dendritic cells (DC), as determined by low cell yield and CD1a expression. MDS-MoDCs exhibited low expression of mannose receptor and reduced endocytic capacity. MDS-MoDCs showed a diminished response to TNF-alpha with low CD83, CD80, and CD54 expression and allostimulatory capacity. In patients with 5q syndrome, monocytes and MoDCs were positive for the 5q deletion, suggesting their origin from the malignant clone. Our data indicate that MoDCs in MDS display quantitative and functional abnormalities that may contribute to the defective immune response of these patients.
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PMID:Defective tumor necrosis factor alpha-induced maturation of monocyte-derived dendritic cells in patients with myelodysplastic syndromes. 1550 96

We have investigated how the maturation of monocyte-derived dendritic cells (Mo-DC) is affected by the serum concentration of the culture medium. Day 6 DC cultured in 1% human serum were a heterogeneous population of CD1a(-) and CD1a(+) DC that were separated by flow sorting. In contrast, Mo-DC generated in 10% human serum formed a homogenous population of CD1a(-) cells. Other phenotypically immature characteristics also varied, and three subsets were still distinguishable upon maturation in LPS. Furthermore, CD1a(-) DC and CD1a(+) DC from 1% culture conditions were excellent stimulators in MLR, while DC cultured in 10% serum were poor stimulators. Similarly, different cytokine profiles of the three subsets were identified. DC cultured in 1% serum had low expression of interleukin-12 (IL-12) p40 and IL-10 mRNA at day 6. Upon maturation, expression of IL-12 p40 mRNA was upregulated in CD1a(+) DC, whereas the level remained relatively low in CD1a(-) DC. In contrast, DC cultured in 10% had high levels of IL-10 mRNA at day 6 that was downregulated upon maturation. We conclude that the differentiation of monocytes into DC is significantly influenced by the serum concentration of the growth medium with effects on phenotype, cytokine profile and stimulatory activity.
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PMID:Serum concentration of the growth medium markedly affects monocyte-derived dendritic cells' phenotype, cytokine production profile and capacities to stimulate in MLR. 1558 69

Recombinant bacterial ghosts loaded with plasmids were tested as an antigen delivery system and as a potential mediator of maturation for human monocyte-derived dendritic cells (DCs). Bacterial ghosts are cell envelopes derived from Gram-negative bacteria; the intracellular content is released by the controlled expression of plasmid-encoded lysis gene E of PhiX174. All the cell surface structures of the native bacteria, including the outer membrane proteins, adhesins, LPS, lipid A, and peptidoglycans, are preserved. Co-incubation of immature DCs with ghosts resulted in decreased expression of CD1a, CD80, and CD83 molecules, while addition of maturation mix (TNF-alpha, IL-1 beta, IL-6, and PGE2) to the cultures enhanced expression of these molecules. No marked changes were observed in the expression of the CD11c, CD40, and CD86 surface molecules. The exposure of DCs to ghosts in combination with maturation mix resulted in a nonsignificant increase in their ability to activate T cells. DCs co-incubated with bacterial ghosts carrying plasmids encoding GFP in combination with maturation mix exhibited high expression levels of GFP (up to 85%). These results indicate that in addition to their well-established use as vaccines, bacterial ghosts can also be used as carriers of nucleic acid-encoded antigens.
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PMID:Bacterial ghosts as novel efficient targeting vehicles for DNA delivery to the human monocyte-derived dendritic cells. 1572 57

Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14(+) cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis.
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PMID:Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis. 1573 Mar 98

Piceatannol is an anti-inflammatory, immunomodulatory, and antiproliferative stilbene that has been shown to interfere with the cytokine signaling pathway. Dendritic cells (DCs) play a pivotal in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. This study investigated the effect of piceatannol on the phenotypic and functional maturation of human monocyte-derived DCs in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days, followed by another 2 days in the presence of piceatannol or LPS. DCs harvested on day 8 were examined using functional assays. The expression levels of CD1a, CD80, CD83, and CD86 as expressed by mean fluorescence intensity (MFI) on DCs differentiated from immature DCs after culture with 1 muM of piceatannol for 2 days were enhanced and decreased endocytic activity. Piceatannol-treated DCs also displayed enhanced T-cell stimulatory capacity in a MLR, as measured by T-cell proliferation. Similar results were obtained with DCs differentiated with LPS from immature DCs. However, piceatannol did not inhibit phenotypic and functional maturation induced by LPS from immature DCs. Piceatannol-treated DCs induced the differentiation of naive T cells towards a helper T-cell type 1 (Th1) response at DCs/T (1:5) cells ratio depending on IL-12 secretion. These results demonstrate that piceatannol may be used on DC-based vaccine for cancer immunotherapy.
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PMID:Effect of piceatannol in human monocyte-derived dendritic cells in vitro. 1579 3

Current immunological opinion holds that myeloid dendritic cell (mDC) precursors migrate from the blood to the tissues, where they differentiate into immature dermal- and Langerhans-type dendritic cells (DC). Tissue DC require appropriate signals from pathogens or inflammatory cytokines to mature and migrate to secondary lymphoid tissue. We show that purified blood mDC cultured in vitro with GM-CSF and IL-4, but in the absence of added exogenous maturation stimuli, rapidly differentiate into two maturational and phenotypically distinct populations. The major population resembles immature dermal DC, being positive for CD11b, CD1a, and DC-specific ICAM-3-grabbing nonintegrin. They express moderate levels of MHC class II and low levels of costimulatory molecules. The second population is CD11b(-/low) and lacks CD1a and DC-specific ICAM-3-grabbing nonintegrin but expresses high levels of MHC class II and costimulatory molecules. Expression of CCR7 on the CD11b(-/low) population and absence on the CD11b(+) cells further supports the view that these cells are mature and immature, respectively. Differentiation into mature and immature populations was not blocked by polymyxin B, an inhibitor of LPS. Neither population labeled for Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells. Stimulation of 48-h cultured DC with LPS, CD40L, or poly(I:C) caused little increase in MHC or costimulatory molecule expression in the CD11b(-/low) DC but caused up-regulated expression in the CD11b(+) cells. In HIV-infected individuals, there was a marked decrease in the viability of cultured blood mDC, a failure to differentiate into the two populations described for normal donors, and an impaired ability to stimulate T cell proliferation.
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PMID:Human BDCA-1-positive blood dendritic cells differentiate into phenotypically distinct immature and mature populations in the absence of exogenous maturational stimuli: differentiation failure in HIV infection. 1594 29

Natural killer T cells (NKT cells) expressing a semi-invariant CD1d-reactive T cell receptor (invariant NKT, iNKT) can be rapidly activated by monocytes or immature dendritic cells (iDCs) bearing a CD1d-presented glycolipid antigen and can in turn stimulate these myeloid cells to mature and produce IL-12. Previous studies have shown that iNKT-produced IFNgamma and CD40 ligand contribute to this dendritic cell maturation. This study demonstrates that CD1d ligation alone, in the absence of iNKT, could rapidly (within 24 h) stimulate production of bioactive IL-12p70 by CD1d+ human peripheral blood monocytes as well as iDCs. IFNgamma alone had no effect, but it markedly enhanced CD1d-stimulated IL-12 production. Monocyte differentiation, as assessed by CD40 and CD1a up-regulation, was also accelerated by CD1d stimulation, consistent with this representing a physiological response. CD1d ligation on the human monocytic cell line THP-1 similarly specifically stimulated IL-12 production. Biochemical studies showed that IL-12 release correlated with rapid phosphorylation of IkappaB, a critical step in NF-kappaB activation. Selective NF-kappaB inhibition blocked this CD1d-stimulated IL-12 production. Finally, CD1d ligation could also enhance IL-12 production in the presence of suboptimal LPS or CD40 stimulation. These findings demonstrate an innate immune signaling function for CD1d and provide a mechanism for the rapid activation of monocytes and iDCs by CD1d-reactive T cells.
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PMID:CD1d ligation on human monocytes directly signals rapid NF-kappaB activation and production of bioactive IL-12. 1609 69


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