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)

Antibodies to the CD6 Ag have been described as having pan-T cell reactivity. We have recently demonstrated, however, that after treatment of PBL with an anti-CD6-blocked ricin-conjugated immunotoxin, clonal populations of CD3+, CD6- cells can be identified. Herein we show that through dual parameter staining of freshly isolated E-rosette+ cells, an average of 5 to 6% of either CD3+ or CD5+ cells express little or no CD6 on their surface. After negative selection by antibody-coated paramagnetic bead depletion, expanded CD6- T cells were shown to be CD1a-, CD2+, CD3+, CD5+, CD16-, CD56-, TCR-gamma/delta-, and consisted of both CD4+ and CD8+ cells. Furthermore, staining of digitonin permeabilized cells showed no cytoplasmic expression of the CD6 Ag and CD6 mRNA was not detected by Northern blot analysis. Identical staining patterns were observed for T cell clones isolated through bead depletion or immunotoxin treatment and expanded with either PHA or immobilized anti-CD3 mAb. It was also found that, relative to unfractionated T cells, the surface expression of CD5 was significantly diminished on CD6- T cells. Functionally, freshly isolated CD6- T cells showed substantially reduced alloreactivity in MLR compared with unfractionated E-rosette+ cells, yet both gave similar proliferative responses to either PHA or soluble tetanus toxin Ag. We conclude that there exists a minor subpopulation of mature T cells in peripheral blood that lack CD6. The diminished alloreactivity of these cells may help to explain the low incidence of graft-vs-host disease, despite high levels of engraftment, that has been reported in allogeneic bone marrow transplant patients receiving marrow treated with anti-CD6 (T12) mAb plus C'.
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PMID:Isolation and characterization of CD6- T cells from peripheral blood. 790 89

Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.
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PMID:Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells. 845 72

Dendritic cells (DC) are the most potent APCs within the immune system. We show here that highly purified CD14(bright) peripheral blood monocytes supplemented with granulocyte-monocyte (GM)-CSF plus IL-4 develop with high efficacy (>95% of input cells) into DC. They neo-expressed CD1a, CD1b, CD1c, CD80, and CD5; they massively up-regulated CD40 (109-fold) and HLA-DQ and DP (125- and 87-fold); and significantly (>5-fold) up-regulated HLA-DR, CD4, CD11b, CD11c, CD43, CD45, CD45R0, CD54, CD58, and CD59. CD14, CD15s, CD64, and CDw65 molecules were down-regulated to background levels, and no major changes were observed for HLA class I, CD11a, CD32, CD33, CD48, CD50, CD86, CDw92, CD93, or CD97. Monocytes cultured in parallel with GM-CSF plus TNF-alpha were more heterogeneous in expression densities but otherwise similar in their surface molecule repertoire. They clearly differed, however, in their accessory cell capacity. Only GM-CSF plus IL-4-cultured cells were found to be potent stimulators in allogeneic and autologous MLR and they presented tetanus toxoid 100- to 1000-fold more efficiently than other cell populations tested. Furthermore, only cytokine-treated monocytes formed clusters with resting T cells. At variance from all these similarities between in vitro-generated monocyte-derived DC and in vivo-developing DC, the DC populations generated by us contained significant amounts of myeloperoxidase and also expressed lysozyme. At least in this respect they, thus, differ from "classical" DC types.
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PMID:Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes. 889 15

Dendritic cells are potent stimulators of Ag-specific T cell responses and have been implicated in the pathogenesis of HIV-1 and other viral infections. Although cytokines may be involved in both of these processes, there is little information on the expression of cytokines by human blood dendritic cells. We characterized cytokine gene and protein expression in dendritic cells that were purified from normal human PBMC by flow cytometry and stimulated in vitro for up to 24 h with HIV-1 or herpes simplex virus (HSV). The unstimulated, uncultured dendritic cells were defined by their phenotype (HLA DR+ CD3- CD19- CD16- CD56- CD14-) and distinct morphology, lack of mRNA expression for CD3, CD14 and CD19, and presence of mRNA for CD4 and CD83. The purified dendritic cells also expressed CD4 (70-90%), CD33 (36-48%), and CD11c (44-54%); lacked CD1a expression (<1%); and were potent stimulators of an allogeneic MLR. The stimulated dendritic cells expressed mRNA for IFN-alpha, IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, GM-CSF, and TNF-alpha within 4 to 12 h as determined by reverse transcription-PCR, with higher levels induced by HSV compared with HIV-1 strains IIIb or BaL. In contrast, the dendritic cells produced detectable protein only for IFN-alpha and IL-6 in response to HIV-1 or HSV, and IL-1beta in response to HSV within 24 h. There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either mock stimulated or stimulated with HIV-1 or HSV for 24 h. Production of IFN-alpha, IL-1beta, and IL-6 by dendritic cells may be important to the immunologic function of these cells and their role in the pathogenesis of HIV-1 and HSV infections.
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PMID:Cytokine expression by human peripheral blood dendritic cells stimulated in vitro with HIV-1 and herpes simplex virus. 889 36

Dendritic cells (DC), with potentially important clinical applications, have been generated from human peripheral blood monocytes in the presence of GM-CSF and IL-4 (G4 DC). In the present report we show that DC with a novel phenotype can be generated from blood adherent mononuclear cells in the presence of GM-CSF and IL-7 (G7 DC). Adherent cells from PBMC, cultured in GM-CSF (600 U/ml) and IL-7 (6 U/ml), were transformed over 7 days into cells with DC morphology, at a yield of 1.2-1.6 x 10(6) per 10(7) PBMC. G7 DC not only expressed class I and class II MHC, CD1a, CD11c, CD23, CD40, CD54, CD58, CD80, CD86 and CD95, like G4 DC, but also CD21, which is the complement receptor type 2, a ligand for CD23 and a receptor for EBV and IFN-alpha. G7 DC were at least one log more effective in the autologous MLR and at least two logs more effective in the allogeneic MLR, than PBMC. They elicited proliferative responses of CD4 T cells to tetanus toxoid and CD8 T cells to an EBV peptide, and stronger T-cell cytotoxicity to EBV peptide than G4 DC. Expression of CD21 by G7 DC suggests that IL-7 delivers a distinct signal to DC precursors and that G7 DC may be functionally distinct.
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PMID:Dendritic cells generated from human blood in granulocyte macrophage-colony stimulating factor and interleukin-7. 936 62

Dendritic cells (DC) are bone marrow derived cells present in diverse tissues and organs including the skin, mucosae and blood. DC have a capital role in the afferent pathway of the immune response because of its role in up-take, processing and presenting antigens to immune cells. Human DC are usually identified by the expression of surface CD1a and HLA-DR. Despite the significant recent developments for in vitro generation of DC derived from blood by using cytokines like GM-CSF and IL-4, the studies on DC and specially on human Langerhans cells (LC) have been hampered by the laborious isolation procedure and the small yield of cells obtained by the various methods of isolation used so far. Therefore, a priority has been a search for monoclonal dendritic cell-lines with LC characteristics in order to facilitate the research in this area. The present study reports on the generation of two stable, self-replicant, adherent, dendritic, CD1a+, HLA-DR , CD45RO , CD23/FcERII+ cell-lines that up-take and process soluble antigens but also inducing MLR and antigen-dependent T-cell response.
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PMID:Characterisation of two human dendritic cell-lines that express CD1a, take-up, process and present soluble antigens and induce MLR. 956 73

This study identifies type I IFNs as activating cytokines in a serum-free system in which human dendritic cells (DC) were generated from CD34+ progenitor cells. After 14 days of culture in GM-CSF, TNF-alpha, and IL-4, CD34+ progenitors gave rise to a population of large, immature DC expressing CD1a and CD11b but lacking CD14, CD80, CD83, CD86, and CMRF44. During the next 2 wk, this population spontaneously matured into nonadherent, CD1a(low/-), CD11b(low/-), CD14-, CD80+, CD83+, CD86+, CMRF44+ DC with high allostimulatory activity in the MLR. To examine which factors influenced this maturation, 25 different cytokines or factors were added to the immature DC culture. Only type I IFNs (alpha or beta) accelerated this maturation in a dose-dependent manner, so that after only 3 days the majority of large cells acquired the morphology, phenotype, and function characteristics of mature DC. Furthermore, supernatants from cultures containing spontaneously maturing DC revealed low levels of endogenous IFN production. Because of the similarity of the activation of DC in our culture system with the phenotypic and functional changes observed during Langerhans cells activation and migration in vivo, we investigated the effect of IFN-alpha on human Langerhans cell migration. IFN-alpha also activated the migration of human split skin-derived DC, demonstrating that this effect was not limited to DC derived in vitro from hemopoietic progenitor cells. DC activation by type I IFNs represents a novel mechanism of immunomodulation by these cytokines, which could be important during antiviral responses and autoimmune reactions.
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PMID:Type I IFNs enhance the terminal differentiation of dendritic cells. 971 65

We examined the effect of interleukin (IL)-4 or CD40 ligation on the differentiation and maturation of CD1a+CD14- and CD1a-CD14+ dendritic cell (DC) precursors. Cord blood CD34+ cells were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha), to which stem cell factor and Flt-3 ligand were added for 5 days. Phenotypic analysis of DC precursors on culture day 7 showed that CD1a+CD14- cells expressed higher CD11c and CD80 levels and lower CD116/GM-CSFR and CCR-5 levels than their CD1a-CD14+ counterparts. Culturing CD1a+CD14- precursors with GM-CSF and TNF-alpha resulted in DC with heterogeneous CD1a, HLA;SMDR (DR), CD11b, and CD83 expression, 10% of which acquired CD14. IL-4 and CD40 ligation affected their differentiation in contrasting ways: IL-4 induced CD1ahiCD14-DRloCD11b+CD83-S100+ DC with reduced MLR-stimulating capacity, whereas CD40 ligation led to CD1alo/-CD14-CD40-DRhiCD11b-CD83+S100+/- DC with stronger MLR-stimulating capacity. Also, both IL-4 and CD40 ligation promoted ReIB expression and nuclear translocation. When CD1a-CD14+ precursors were maintained in only the presence of GM-CSF and TNF-alpha, this led to mixed populations of adherent macrophages and nonadherent CD1a-CD14+ monocytes, and of CD1a+CD14- and CD1a+CD14+ DC, which were DRloCD11b+CD83-S100-. IL-4 or CD40 ligation prevented their differentiation into macrophages and resulted in DC with phenotypes close to those issued from CD1a+CD14- precursors, with only a minority staying CD14+ but most being S100-; their MLR-stimulating capacity also increased but remained lower than that of DC differentiated from CD1a+CD14- precursors. Thus, IL-4 or CD40 ligation induced CD1a+CD14- and CD1a-CD14+ DC precursors to differentiate into phenotypically close but functionally different DC populations, suggesting that DC function is primarily determined by their origin. The heterogeneity of DC should then be related to different developmental pathways and to different stages of maturation/activation.
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PMID:IL-4 and CD40 ligation affect differently the differentiation, maturation, and function of human CD34+ cell-derived CD1a+CD14- and CD1a-CD14+ dendritic cell precursors in vitro. 971 64

Whether thymic dendritic cells (DC) are phenotypically and functionally distinct from the monocyte lineage DC is an important question. Human thymic progenitors differentiate into T, NK, and DC. The latter induce clonal deletion of autoreactive thymocytes and therefore might be different from their monocyte-derived counterparts. The cytokines needed for the differentiation of DC from thymic progenitors were also questioned, particularly the need for GM-CSF. We show that various cytokine combinations with or without GM-CSF generated DC from CD34+CD1a- but not from CD34+CD1a+ thymocytes. CD34+ thymic cells generated far fewer DC than their counterparts from the cord blood. The requirement for IL-7 was strict whereas GM-CSF was dispensable but nonetheless improved the yield of DC. CD14+ monocytic intermediates were not detected in these cultures unless macrophage-CSF (M-CSF) was added. Cultures in M-CSF generated CD14-CD1a+ DC precursors but also CD14+CD1a- cells. When sorted and recultured in GM-CSF, CD14+ cells down-regulated CD14 and up-regulated CD1a. TNF-alpha accelerated the differentiation of progenitors into DC and augmented MHC class II transport to the membrane, resulting in improved capacity to induce MLR. The trafficking of MHC class II molecules was studied by metabolic labeling and immunoprecipitation. MHC class II molecules were transported to the membrane in association with invariant chain isoforms in CD14+ (monocyte)-derived and in CD1a+ thymic-derived DC but not in monocytes. Thus, thymic progenitors can differentiate into DC along a preferential CD1a+ pathway but have conserved a CD14+ maturation capacity under M-CSF. Finally, CD1a+-derived thymic DC and monocyte-derived DC share very close Ag-processing machinery.
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PMID:Functional and phenotypic analysis of thymic CD34+CD1a- progenitor-derived dendritic cells: predominance of CD1a+ differentiation pathway. 1022 16

We recently demonstrated that dendritic cells (DCs) can be generated from monocytes in the presence of high concentrations of human serum (HS), provided the extra-cellular pH is maintained at plasma values. Because monocyte-derived DCs (Mo-DCs) can also be generated in the presence of fetal calf serum (FCS) or serum-free medium, we have investigated whether these different culture supplements influence DC generation. With this aim, purified monocytes were cultured with GM-CSF plus IL-4 for 6 days and were further exposed to TNF-alpha for 2 additional days, in the presence of HS, autologous plasma (AP), FCS, or X-VIVO 20, a serum-free medium. Our results show that good yields of functionally mature DCs can reproducibly be obtained in the presence of HS or AP, as assessed by CD83 and CD86 up-regulation, dextran-FITC uptake, allogeneic MLR assays and the induction of an autologous response. Interestingly, the effect of serum on DC generation was probably not only quantitative, but also qualitative, since (i) the majority of HS- or AP-cultured DCs expressed CD83 with very weak levels of CD1a, whereas CD83+ DCs cultured in FCS or X-VIVO were mostly CD1a++; (ii) HS- and AP-cultured DCs were much more granular and heterogeneous than FCS- or X-VIVO-cultured DCs, and (iii) the presence of Birbeck-like granules was preferentially observed in HS- or AP-cultured DCs, as assessed by electron microscopy. That these different cells resemble dermal DCs (DDCs) was further supported by the observations that most of the cells displayed intracytoplasmic FXIIIa in the absence of Lag antigen, and expressed E-cadherin at very low levels. Altogether, our results indicate that starting from the same monocytic population, different subsets of DCs can be generated, depending on the culture conditions. Thus, HS or AP favors the generation of fully mature DCs that resemble activated dermal DCs, whereas FCS, or X-VIVO preferentially leads to the generation of less mature CD1a++ dermal-like DCs.
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PMID:Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements. 1075 42


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