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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cell binding to target cells involves not only the TCR and its MHC-bound ligand, but also a collection of additional proteins on both the T cell and its target. In an attempt to identify new molecules involved in this binding, mAb were raised against APC, and screened for their abilities to inhibit T cell recognition of Ag plus MHC on B cells. Six antibodies were identified that inhibited this reaction and that bound a cell-surface glycoprotein (Lgp55), with core polypeptide Mr 30,000 and a glycosylated Mr of approximately 55,000 depending upon the cell source. The properties of Lgp55 were consistent with it being the mouse homologue of a recently identified human ligand (intercellular adhesion molecule-2) for lymphocyte functional Ag-1 because the proteins are of comparable Mr, and antibody to Lgp55, like anti-lymphocyte functional antigen-1, blocks T cell recognition of Ag presented by B cells, but not of Ag presented by mouse fibroblasts.
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PMID:Identification of a new cell surface glycoprotein with accessory function in murine T cell responses. 213 99

Dendritic cells (DC) are the principle APC involved in primary immune responses; their major function is to obtain Ag in tissues, migrate to lymphoid organs, and activate T cells. DC are also the first immune cells to arrive at sites of inflammation on mucous membranes, the major site of sexual transmission of HIV. We have demonstrated previously that three populations of cells that can develop a dendritic morphology are present in peripheral blood. Two of these populations can express CD83, a marker of DC, and appear to be at different stages of maturation: 1) a precursor population and 2) a mature immunostimulatory DC. Precursor-derived DC express high levels of CD86 (B7-2) and HLA-DR but no CD80 (B7-1), whereas mature DC have high levels of expression of all three markers. Mature DC in peripheral blood bind HIV to their surface and induce infection when added to autologous CD4+ T cells in the absence of added stimuli, such as mitogens. These mature DC, when isolated directly from peripheral blood, appear to be conjugated to T cells, and these conjugates are infected easily and productively with HIV. These findings suggest a role for DC in early HIV infection in which they bind virus and interact with T cells locally or after migrating to a lymphoid organ, thus establishing a productive infection. Furthermore, they likely play a role in the propagation of HIV infection by activating T cells in the presence of HIV, which leads to viral replication and immune cell destruction.
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PMID:Both a precursor and a mature population of dendritic cells can bind HIV. However, only the mature population that expresses CD80 can pass infection to unstimulated CD4+ T cells. 756 Nov 24

Dendritic cells are potent APC that initiate primary T cell-dependent immune responses. The lack of lineage-associated cell surface Ags for human dendritic cells has made characterization of this lineage difficult. In this study, analysis of leukocyte subpopulations isolated from human blood revealed that circulating or cultured B and T cells, NK cells, and monocytes did not express CD83, whereas CD83+ cells were predominantly found in the dendritic cell-enriched metrizamide low density fraction of plastic nonadherent blood mononuclear cells. Blood CD83+ cells had a cellular morphology characteristic of dendritic cells and a cell surface phenotype that did not correlate with that of T cells, B cells, NK cells, or cells of the myelomonocytic lineage. Analysis of CD83+ cells with a panel of mAbs that identify 126 leukocyte cell surface Ags revealed the CD83+ cells to be a phenotypically homogeneous and unique population of cells that expressed the highest levels of MHC class II molecules when compared with other leukocyte lineages. CD83+ cells were also the most potent stimulator cells in an allogeneic MLR when compared with other leukocyte lineages. Functional analysis of CD83+ cells revealed that MHC class II, CD11a, CD40 and CD86 played functionally dominant roles, whereas CD80 contributed minimally to the specialized costimulatory activity of these potent APC. Thus, CD83 serves as a useful and specific marker for this unique population of human blood dendritic cells.
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PMID:Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. 770 22

We have investigated an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The procedure uses 1% human plasma in the place of 10% fetal calf serum and involves two steps. The first step or 'priming' phase is a 6-7 day culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The second step or 'differentiation' phase requires the exposure to macrophage conditioned medium. This medium cannot be replaced by several known cytokines such as TNF-alpha, IL-1, IL-6, IL-12 and IL-15, and cannot be inhibited with neutralizing antibodies to IL-1, TNF-alpha, IL-6 or IL-12 alone, or in combination. Using this two-step approach, we obtain substantial yields. About 1-3 x 10(6) mature dendritic cells are generated from 40 ml of blood vs. < 0.1 x 10(6) from noncytokine treated blood. The dendritic cells derive from progenitors found primarily in a radioresistant population of CD14+ and adherent blood mononuclear cells and have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. Strong APC function was evident for both the proliferation of allogeneic T cells in the MLR, and the generation by syngeneic T cells of class I restricted, CTL responses to influenza virus. A panel of dendritic cell restricted markers is also expressed, including CD83, p55, and perinuclear CD68. All of these dendritic cell properties are retained for at least 3 days when the cytokines are removed, suggesting that these populations are stable and terminally differentiated. We suggest that these cells will be effective in vivo as adjuvants for active immunotherapy.
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PMID:Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. 884 51

Dendritic cells (DC) form a specialized system for presenting Ag to naive or quiescent T cells and consequently play a central role in the induction of T and B cell immunity. In this study we used DC generated from peripheral progenitors to analyze the effect of IL-10 on the accessory function of human DC. We demonstrate that immature DC, harvested on days 9 to 11 and exposed to IL-10 for the last 2 days of culture, show a strongly reduced capacity to stimulate a CD4+ T cell response in an allogeneic MLR in a dose-dependent manner. In contrast, fully mature DC are completely resistant to the effects of IL-10. These results were obtained in both an alloantigen-induced MLR and an anti-CD3 mAb-induced response of primed and naive (CD45RA+) CD4+ T cells. FACS analysis revealed inhibition of the up-regulation of the costimulatory molecules CD58 and CD86 and the specific DC marker CD83 in DC pretreated with IL-10. These data suggest that IL-10 inhibited the development of fully mature DC. Furthermore, DC precultured with IL-10, but not controls, induced a state of alloantigen-specific anergy in CD4+ T cells and of peptide-specific anergy in the influenza hemagglutinin-specific T cell clone HA1.7. Analysis of the supernatants of these anergic T cells revealed a reduced production of IL-2 and IFN-gamma compared with that in control cells. Collectively, these data suggest that IL-10 converts immature DC into tolerogenic APC, which might be a useful tool in the therapy of patients with autoimmune or allergic diseases.
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PMID:Induction of tolerance by IL-10-treated dendritic cells. 936 1

Human peripheral blood contains a small subpopulation of immature dendritic cells (iDC) distinguished from circulating monocytes by their low expression of CD14. We utilized leukapheresis and countercurrent centrifugal elutriation to obtain myeloid origin mononuclear cell (MOMC) fractions of monocytes and iDC for study. These subpopulations were ultrastructurally and immunophenotypically similar before culture. After a 20- to 96-h culture either alone, with recombinant human granulocyte-monocyte CSF, or with endotoxin, greater up-regulation of costimulatory molecule expression was observed among iDC than among monocytes, and only iDC expressed the activation molecule CD83. Treatment with rhIL-4 caused many MOMC to develop morphologic properties of dendritic cells within 96 h, but costimulatory molecule up-regulation and CD14 down-regulation were heterogeneous, and CD83 expression was infrequent. In contrast, calcium ionophore (CI) treatment induced rapid and consistent effects in MOMC from both healthy volunteers and cancer patients, including down-regulated CD14 expression, acquisition of dendritic cell morphologic properties, up-regulated MHC and costimulatory molecule expression, and de novo CD83 expression. Many such effects occurred within 20 h of treatment. CI treatment activated purified CD14+ monocytes and also enhanced the spontaneous activation of purified CD14-/dim iDC in culture. Unfractionated MOMC, purified monocytes, and purified iDC displayed equivalently enhanced T cell-sensitizing efficiency following CI treatment. CD4+ T cell sensitization to keyhole limpet hemocyanin and CD8+ T cell sensitization to MART-1 melanoma-associated peptide were achieved in a single culture stimulation. Therefore, circulating monocytes and iDC can be induced by CI to manifest properties of activated DC, providing large numbers of efficient, nontransformed autologous APC for T cell sensitization strategies.
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PMID:Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells. 937 70

OX40 ligand (OX40L), a member of the TNF family, was shown to be capable of signaling both the cells on which it is expressed and those expressing OX40, its cognate receptor. Here we show that OX40L is expressed on dendritic cells (DC), the most efficient APC to prime naive T cells. The expression and the functional activity of OX40L were examined by means of mAbs used to stain or cross-link OX40L on 1) freshly isolated human blood DC (bDC) and 2) monocyte-derived DC at different stages of differentiation. These were derived from monocytes cultured either with IL-4 and granulocyte-macrophage CSF (IL-4-Mo-DC) or with IL-4 and granulocyte-macrophage CSF plus TNF-alpha. Both types of Mo-DC expressed OX40L after stimulation through CD40; ligation of OX40L on activated IL-4-Mo-DC enhanced by 4- to 35-fold their cytokine production (TNF-alpha, IL-12 p40, IL-1 beta, and IL-6) and increased CD80, CD86, CD54, and CD40 expression. Stimulation of activated IL-4-Mo-DC through OX40L strikingly enhanced their maturation as evidenced by CD83 up-regulation, CD115 (CSF-1R) down-regulation, and typical morphologic changes. OX40L was constitutively expressed on a subset of bDC, and its ligation slightly enhanced CD40L-stimulated IL-12 production. OX40L was down-regulated after overnight culture and spontaneously reexpressed on a subset of mature bDC (CD83high, CD33high, CD11chigh, CD5+). Thus, the expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation.
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PMID:Expression and function of OX40 ligand on human dendritic cells. 937 71

Loci conferring susceptibility to schizophrenia, coeliac disease, and orofacial clefting have been assigned to the 6p23-p25 region of human chromosome 6. To facilitate the identification of candidate genes we have sublocalized and ordered 39 ESTs assigned to this interval by radiation hybrid mapping. This was achieved by generating PAC contigs containing the ESTs, genetic markers, and random STSs. For full integration into previously published data a single YAC contig spanning 6p23-p25 was used to unambiguously order the PAC contigs and ESTs along the chromosome. The majority of the ESTs (31/39) were positioned in the 6p23-p24 interval at the proximal half of the map, and of these 8 are located within a single PAC clone. The order of known genes in this region is cen-CD83-ZNF40-EDN1-(GCNT2, CAPZB)-TFAP2-BMP6-DSP-tel.
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PMID:Fine mapping of 39 ESTs on human chromosome 6p23-p25. 941 21

We describe a subset of peripheral CD14+ cells, coexpressing the CD34 progenitor marker and able to migrate across endothelial cell monolayers. On culture with granulocyte-macrophage-CSF, this population differentiated into dendritic cells expressing CD83, CD80, HLA-DR(bright), CD86, and CD54. These dendritic cells were immunostimulatory, in that they induced proliferation of allogenic and tetanus toxoid-specific T lymphocytes. The CD14+ CD34+ population expressed higher levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha4beta1 integrin than the CD14+ CD34- counterpart, being dull positive for other integrins. Using stably transfected PECAM-1+, VCAM-1+, or ICAM-1+ cells, we found that PECAM-1 and, to a lesser extent, VCAM-1, could support transmigration of CD14+ CD34+ cells, whereas the alphaL-ICAM-1 interaction was involved in cell adhesion. PECAM-1-driven transmigration was conceivably dependent on a haptotactic gradient, as it was reduced by 80% across NIH3T3 cells transfected with the PECAM-1-delta cyto deletion mutant. This mutant lacks the cytoplasmic tail and displays a reduced tendency to localize at the intercellular junctions, thus failing to form a molecular junctional gradient. Once differentiated, dendritic cells derived from CD14+ CD34+ precursors retained their transendothelial migratory capability, using both PECAM-1 and ICAM-1 for transmigration. We suggest that a subset of CD14+ CD34+ circulating leukocytes can localize to peripheral tissues and differentiate into functional dendritic cells, thus representing a functional reservoir of potential APC. PECAM-1, constitutively expressed on vascular endothelium, is likely to play a relevant role in the egress of this population from the bloodstream.
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PMID:CD14+ CD34+ peripheral blood mononuclear cells migrate across endothelium and give rise to immunostimulatory dendritic cells. 951 Jan 66

The CTL response to HIV-I can be vigorous, but antigen presenting cell requirements have not been studied in detail. To approach this question, we have examined the dendritic cell populations that can be obtained from the blood of HIV-1 infected individuals. We studied 13 asymptomatic patients, who spanned a wide range of plasma viremia and CD4 counts. We show here that sizeable numbers of mature dendritic cells can be generated from nonproliferating progenitors in the blood of HIV + patients using a recently developed approach. The procedure involves two steps. The first step or 'priming' phase is a 7 day culture of T-cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The second step or 'differentiation' phase requires the exposure to monocyte conditioned medium. The yields of DCs from HIV + individuals were comparable to normal blood donors, 0.4 - 3 x 10(6) mature dendritic cells from 50 ml of blood. Strong APC function was evident for both the proliferation of allogeneic T-cells in the MLR, and the generation by syngeneic T-cells of class I restricted, CTL responses to influenza virus. A panel of dendritic cell restricted markers are expressed, including CD83, p55, and perinuclear CD68. By semi-quantitative PCR analysis, the cytokine derived cells did not express HIV-1 DNA. We suggest that these blood derived dendritic cells will be effective for studies of immune responses to HIV-1 antigens and may be considered as adjuvants for active immunotherapy.
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PMID:Dendritic cells generated from blood monocytes of HIV-1 patients are not infected and act as competent antigen presenting cells eliciting potent T-cell responses. 1020 44


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