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)

Neonates are relatively immature in their immune response; thus, to further clarify the differences of monocyte function and differentiation between neonates and adults, we investigated their CD14(+)CD4(+) and CD14(+)CD16(+) monocyte subpopulations, production of IL-1beta and tumor necrosis factor-alpha induced by lipopolysaccharide, and their CD14 and CD1a phenotypic changes in response to IL-4 and granulocyte-macrophage colony-stimulating factor. Our results showed that 1) the expression of CD14 in cord blood monocytes was significantly lower than that in adult peripheral blood monocytes; 2) both the percentages of CD14(+)CD4(+) cells and CD14(+)CD16(+) cells among CD14(+) monocytes were also significantly lower in cord blood; 3) after stimulation by lipopolysaccharide for 72 h, production of both IL-1beta and tumor necrosis factor-alpha was lower in cord blood than that in adult peripheral blood; and 4) in response to IL-4 or GM-CSF, the phenotype development of CD14 and CD1a in cord blood and adult peripheral blood was different. Down-regulation of CD14 expression in response to IL-4 and GM-CSF was slower in cord blood monocytes than that in adult peripheral blood monocytes. After 9 d of culture in the presence of IL-4 and GM-CSF, the percentage of CD1a(+) monocytes was significantly more increased in cord blood than that in adult peripheral blood. The reduced expression of CD14 and other mature phenotype markers such as CD16 and CD4 as well as the reduced IL-1beta and tumor necrosis factor-alpha production may contribute to the impaired immune response of neonates. Slower down-regulation of CD14 by IL-4 and GM-CSF suggests that differential properties of cord blood monocytes in response to cellular stress signals take a longer time than those of adult peripheral blood monocytes.
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PMID:Changes of CD14 and CD1a expression in response to IL-4 and granulocyte-macrophage colony-stimulating factor are different in cord blood and adult blood monocytes. 1147 1

Notch-mediated cellular interactions are known to regulate cell fate decisions in various developmental systems. A previous report indicated that monocytes express relatively high amounts of Notch-1 and Notch-2 and that the immobilized extracellular domain of the Notch ligand, Delta-1 (Delta(ext-myc)), induces apoptosis in peripheral blood monocytes cultured with macrophage colony-stimulating factor (M-CSF), but not granulocyte-macrophage CSF (GM-CSF). The present study determined the effect of Notch signaling on monocyte differentiation into macrophages and dendritic cells. Results showed that immobilized Delta(ext-myc) inhibited differentiation of monocytes into mature macrophages (CD1a+/-CD14+/- CD64+) with GM-CSF. However, Delta(ext-myc) permitted differentiation into immature dendritic cells (CD1a+CD14-CD64-) with GM-CSF and interleukin 4 (IL-4), and further differentiation into mature dendritic cells (CD1a+CD83+) with GM-CSF, IL-4, and tumor necrosis factor-alpha (TNF-alpha). Notch signaling affected the differentiation of CD1a-CD14+ macrophage/dendritic cell precursors derived in vitro from CD34+ cells. With GM-CSF and TNF-alpha, exposure to Delta(ext-myc) increased the proportion of precursors that differentiated into CD1a+CD14- dendritic cells (51% in the presence of Delta(ext-myc) versus 10% in control cultures), whereas a decreased proportion differentiated into CD1a-CD14+ macrophages (6% versus 65%). These data indicate a role for Notch signaling in regulating cell fate decisions by bipotent macrophage/dendritic precursors.
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PMID:The Notch ligand, Delta-1, inhibits the differentiation of monocytes into macrophages but permits their differentiation into dendritic cells. 1152 Jul 88

Dendritic cells (DC) with potentially important clinical applications have been generated from human peripheral blood monocytes and CD34(+) cells in the presence of recombinant cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) and GM-CSF + tumor necrosis factor-alpha (TNF-alpha), respectively. Many of the studies generating DC have included fetal calf serum, which is not desirable due to the risk of immune reactions and infectious disease transmission. Additionally, low DC yields have been reported using serum-free media. In this study, we investigate supplementing serum-free media with autologous serum and plasma for DC generation from monocytes and CD34(+) cells. Our results show that functional DC can be reproducibly obtained in the presence of autologous serum using monocytes and CD34(+) cells as the starting populations. However, with the addition of autologous serum, a differential effect is observed in the phenotypic characterization of these culture-derived DC. Monocytes cultured for 7 days in X-VIVO 15 serum-free media in the presence of GM-CSF + IL-4 showed down-regulation of CD14 with increased expression of HLA-DR, mannose receptor, CD80, and CD86, along with highly up-regulated CD1a(+) expression. The addition of autologous serum to serum-free media in monocyte cultures resulted in a dose-dependent decrease in the CD1a(+) expression generating a distinct subset of CD1a(+/-) cells expressing HLA-DR, mannose receptor, CD80, and CD86. Upon stimulation with CD40L cells, both monocyte-derived DC subsets CD1a(+/-) and CD1a(++) were capable of maturation measured by CD83 and CD86 up-regulation. Data suggest the differences in the monocyte-derived DC in serum-free (CD1a(++)) or autologous serum (CD1a(+/-)) supplemented cultures is of a qualitative nature, rather than quantitative. CD1a(+) and CD14(+) cells expressing HLA-DR, mannose receptor, CD80, and CD86 were generated in 7 days from CD34(+) cells in serum-free media. A quantitative effect was obtained when cultures were supplemented with autologous serum, resulting in a significant enhancement of CD34-derived DC generated. These results demonstrate generation of DC from two different starting populations using serum-free media that can be enhanced with the addition of autologous serum. Interestingly, a differential effect was observed in the phenotypic characterization of these culture-derived DC.
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PMID:Differential effects of autologous serum on CD34(+) or monocyte-derived dendritic cells. 1152 39

Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that utilizes IL-2Rgamma chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a(+)HLA-DR(+)CD14(-)DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)alpha, and CD40L induce maturation of IL15-DCs to CD83(+), DC-LAMP(+) cells. IL15-DCs are potent antigen-presenting cells able to induce the primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu-matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4 (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin, and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate in response to macrophage inflammatory protein (MIP)-3alpha/CCL20. However, IL15-DCs cannot be qualified as "genuine" Langerhans cells because, despite the presence of the 43-kD Langerin, they do not express bona fide Birbeck granules. Thus, our results demonstrate a novel pathway in monocyte differentiation into dendritic cells.
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PMID:Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. 1158 22

Experimental protocols for cancer immunotherapy include the utilization of autologous monocyte-derived dendritic cells (moDC) pulsed with tumor antigens. However, disease can alter the characteristics of monocyte precursors and some patients have increased numbers (up to 40%) of the minor CD16(+) monocyte subpopulation, which in healthy individuals represent 10% of blood monocytes. At the present, the capacity of CD16(+) monocytes to differentiate into DC has not been evaluated. Here, we investigated the ability of CD16(+) monocytes cultured with granulocyte- macrophage colony-stimulating factor, IL-4 and tumor necrosis factor-alpha to generate DC in vitro, and we compared them to DC derived from regular CD16(-) monocytes. Both monocyte subsets gave rise to cells with DC characteristics. They internalized soluble and particulate antigens similarly, and both were able to stimulate T cell proliferation in autologous and allogeneic cultures. Nevertheless, CD16(+) moDC expressed higher levels of CD86, CD11a and CD11c, and showed lower expression of CD1a and CD32 compared to CD16(-) moDC. Lipopolysaccharide-stimulated CD16(-) moDC expressed increased levels of IL-12 p40 mRNA and secreted greater amounts of IL-12 p70 than CD16(+) moDC, whereas levels of transforming growth factor-beta1 mRNA were higher on CD16(+) moDC. Moreover, CD4(+) T cells stimulated with CD16(+) moDC secreted increased amounts of IL-4 compared to those stimulated by CD16(-) moDC. These data demonstrate that both moDC are not equivalent, suggesting either that they reach different stages of maturation during the culture or that the starting monocytes belong to cell lineages with distinct differentiation capabilities.
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PMID:CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. 1171 98

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

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

The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207(+) LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC-lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-beta1, we further found that tumor necrosis factor (TNF)-alpha, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC-LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.
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PMID:Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin. 1218 34

Immature dendritic cells (DCs) reside in interstitial tissues (int-DC) or in the epidermis, where they capture antigen and, thereafter, mature and migrate to draining lymph nodes (LNs), where they present processed antigen to T cells. We have identified int-DCs that express both TRANCE (tumor necrosis factor-related activation-induced cytokine) and RANK (receptor activator of NF-kappaB) and have generated these cells from CD34(+) human progenitor cells using macrophage colony-stimulating factor (M-CSF). These CD34(+)-derived int-DCs, which are related to macrophages, are long-lived, but addition of soluble RANK leads to significant reduction of cell viability and Bcl-2 expression. This suggests that constitutive TRANCE-RANK interaction is responsible for CD34(+)-derived int-DC longevity. Conversely, CD1a(+) DCs express only RANK and are short-lived. However, they can be rescued from cell death either by recombinant soluble TRANCE or by CD34(+)-derived int-DCs. CD34(+)-derived int-DCs mature in response to lipopolysaccharide (LPS) plus CD40 ligand (L) and become capable of CCL21/CCL19-mediated chemotaxis and naive T-cell activation. Upon maturation, they lose TRANCE, making them, like CD1a(+) DCs, dependent on exogenous TRANCE for survival. These findings provide evidence that TRANCE and RANK play important roles in the homeostasis of DCs.
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PMID:Long-lived immature dendritic cells mediated by TRANCE-RANK interaction. 1239 86

Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of beta(2)-microglobulin (beta(2)M) and activation or inhibition of the immune system. We hypothesized that beta(2)M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of beta(2)M on monocyte-derived dendritic cells (MoDCs). The addition of beta(2)M (more than 10 microg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, beta(2)M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. beta(2)M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-alpha and IL-1beta. During cell culture, beta(2)M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-kappaB (NF-kappaB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that beta(2)M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.
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PMID:Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. 1253 97


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