UMLS:C0033036 - FACTA Search

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

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

Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4+ T cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45lowCD11b/c+ is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45highCD11b/c+) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45highCD11b/c+ transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4+ myelin basic protein (MBP)-reactive T cells. CD45highCD11b/c+ CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture, suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4+ T cells to proliferate or secrete IL-2.
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PMID:Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. 772 89

After BMT, donor T cells are activated which can display GvHD as well as GvL activities. In order to study this GvL-specific T-cell response in vitro, proliferative T-cell clones from post-BMT PBMCs were generated by stimulation with a patient's leukemic cells. One CD4+ T-cell clone (designated M-33) displayed strong proliferative activity against the patient's leukemic cells but not against the patient's EBV-LCLs. The induction of proliferation, however, appeared not to be leukemia specific. Detailed analysis of the reactivity patterns revealed that T-cell clone M-33 recognizes an as yet unknown nonpolymorphic determinant in the context of self HLA-DRw52, presented by all but one type of APC. T-cell clone M-33 proliferated upon stimulation by PB-MCs, freshly isolated B cells, monocytes, dendritic cells, leukemic B cells, and nonleukemic B-cell blasts; solely in vitro EBV-transformed B cells and in vivo EBV-infected B cells failed to induce proliferation of T-cell clone M-33. Neither surface expression of MHC or accessory molecules on the EBV cells nor suppression caused by the EBV-infected cells could explain their failure to stimulate T-cell clone M-33. We therefore hypothesize that the absence of the stimulatory capacity once the B cells are virally infected could be the result of competition for MHC class II binding of the Epstein-Barr viral peptides, thus affecting the postulated DRw52-restricted peptide for recognition by T-cell clone M-33.
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PMID:Epstein-Barr virus infection abrogates the stimulatory capacity of B cells to a major histocompatibility complex class-II-restricted proliferative T-cell clone. 774 17

MHC class II (MHC-II) molecules bind fragments of exogenous Ags in an intracellular endocytotic compartment. In view of divergent data on the MHC-II distribution in different cell lines, it was of interest to localize MHC-II molecules in a natural and the most potent APC type, the dendritic cell (DC). By using immunogold labeling of ultrathin cryosections of cultured mouse spleen DC, we found that MHC-II molecules were present abundantly at the plasma membrane and in intracellular compartments containing internal membrane vesicles and/or membrane sheets. The majority of these compartments was situated late in the endocytotic route, as demonstrated by the late appearance (after a lag of 30 min) of internalized exogenous tracer. These compartments contained the lysosomal enzymes cathepsin D and beta-hexosaminidase, but lacked the late endosomal marker cation-dependent mannose-6-phosphate receptor. We conclude that most of the intracellular MHC-II molecules in cultured spleen DC reside in a compartment with (pre)lysosomal characteristics, resembling the so-called MHC-II-enriched compartments (MIIC), originally described in B cells. We also investigated whether the presence of MHC-II molecules in endocytotic compartments was related to the kinetics of Ag processing and presentation by these cells. Pulse-chase endocytosis experiments with hen egg lysozyme (HEL) as a model Ag showed that activated spleen DC were able to efficiently process and present this Ag to an HEL-specific T hybridoma cell line. However, presentation started only after a lag of 2 h and was maximal after 6 h. The difference in time between the arrival of Ag in proteolytic endocytotic compartments, in particular MIIC, and effective Ag presentation is discussed in the context of DC maturation.
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PMID:MHC class II compartments and the kinetics of antigen presentation in activated mouse spleen dendritic cells. 775 23

Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4+ T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4+ T cells that remain in the 3-day thymectomized animal revealed that the majority (approximately 80%) of the CD4+ lymph node cells express an activated (MEL-14low) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4+ IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease.
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PMID:Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells. 775 94

The mouse beta 2-microglobulin (m beta 2-m) peptide corresponding to residues 25-40 binds to the MHC class II molecules I-Ad and I-Ed and is immunogenic in BALB/c beta 2-m-deficient but not in normal BALB/c mice. The self-m beta 2-m peptide 25-40 is presented by both I-Ad and I-Ed class II molecules as demonstrated by the activation of T cell hybridomas specific for this sequence obtained from beta 2-m knock-out mice. By analyzing the effect of N- and C-terminal truncations of m beta 2-m25-40 on binding to class II molecules and on activation of T cell hybridomas, the minimum epitopes recognized by I-Ad and I-Ed-restricted T cells are included within amino acid residues 26-39 and 24-36, respectively. Both sets of T hybridomas are also activated by the corresponding naturally processed self-epitope presented by APC from BALB/c mice and from other H-2d strains, irrespective of their Mls phenotype. Therefore, the sequence 25-40 contains dominant naturally processed self-epitopes of the mouse beta 2-m. Processing of endogenous m beta 2-m is sensitive to protease inhibitors and lysosomotropic amines, and is not caused by reuptake of shed or released protein. These results indicate that self-beta 2-m-peptide-MHC class II complexes derive from constitutive processing of the endogenous intracellular pool of m beta 2-m in an acidic endosomal compartment. Antigenic complexes between m beta 2-m peptides and I-Ad or I-Ed class II molecules are constitutively expressed by APC of different tissues, including the thymus, and they are able to induce T cell tolerance, as shown by the lack of T cell response to m beta 2-m25-40 in BALB/c mice.
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PMID:Constitutive presentation of dominant epitopes from endogenous naturally processed self-beta 2-microglobulin to class II-restricted T cells leads to self-tolerance. 781 67

CD4+ T cell clones were generated to tetanus toxin or to two tetanus toxin-derived peptides p2 (AA 830-834) and p30 (AA 947-976). 11 of the 24 p30-specific clones reacted to shorter p30 subunits (p301 or p302), and only 14 of the p2 or p30-specific clones reacted with TT presented by EBV-transformed B cell lines (B-LCL). The p30-specific clones were HLA-DP4 restricted. In contrast to autologous B cell lines, the majority of allogeneic, but HLA-DP4-positive cell lines failed to present p30 to the specific clones. We concluded that T cell clones are highly specific and that both, small alterations of the peptide length as well as discrete differences of the HLA-molecule may abrogate recognition of the peptide HLA complex by T cells. Moreover, use of peptides as stimulators of T cells may recruit and activate T cells which fail the "original" peptide, derived from normal antigen processing. Clones could usually be maintained in culture for 4-6 months, but with the help of freezing and thawing some clones are now available for over 2 years and still specific. Comparison of different autologous antigen-presenting cells, namely B-LCL and activated MHC class II-positive T cells revealed that not all clones were able to mount a proliferative response to peptide presentation by T cells, while all clones proliferated to B cells as APC. If stimulated with peptide and B-LCL, the clone proliferating to T cells as APC (so-called T responder clones) secreted a broad spectrum of cytokines (Th0-like) and were easier to maintain in culture. In contrast, clones which were unable to proliferate to peptide presentation, so-called T-nonresponder clones, showed a more restricted cytokine pattern and elevated or very low IL4/IFN gamma ratio upon antigen specific stimulation. However, all clones secreted at least small amounts of IL2, IL4, IFN gamma and TNF alpha, if stimulated by PMA and ionomycin. Thus, both chemical and antigen-specific stimulations should be considered if T cell clones are classified as Th1 or Th2, whereby those clones, which secrete a limited cytokine pattern after antigen stimulation only, might be named Th1 or Th2 like clones, while clones which even after PMA/ionomycin do not secrete all cytokines, might represent "real" Th1 or Th2 clones.
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PMID:Peptide-induced T cell clones: specificity, MHC restriction, proliferation and cytokine pattern as a function of different stimulations. 787 53

This study demonstrates that a syngeneic specific cytotoxic T lymphocyte (CTL) response to a class I major histocompatibility complex (MHC) positive tumour requires dual processing and recognition of tumour antigens. One type of antigen is processed and expressed in association with class I MHC at the surface of intact tumour cells. It is recognized by CD8 alpha, beta TCR CTL in vitro and by protective immune T cells in vivo and thus functions as a tumour-associated transplantation antigen (TATA). The other type of antigen is processed and expressed by distinct host APC in association with class II MHC. This is recognized by immune CD4 T cells which function as essential helper cells in the generation of the CD8 CTL response. These conclusions are supported by cell depletion and reconstitution experiments as well as by blocking experiments with monoclonal antibodies using the highly metastatic class II negative murine lymphoma ESb as a model system. The existence of two types of cognate T cell responses in a syngeneic anti-tumour response was directly proved by the establishment of two types of tumour specific T cell lines which required as co-stimulator either MHC class II positive APC or IL-2. In suboptimal mixed lymphocyte tumour cell cultures either of these co-stimulator functions was found to be limiting the overall anti-tumour CTL response. The generation of the tumour specific CTL response could be blocked by monoclonal antibodies against all the molecules involved in the cognate interactions (i.e. class I MHC, CD8, class II MHC, CD4 and TCR) but not by anti-CD2 or anti-IgG. The strict requirement for helper cells and APC could be bypassed by the addition of recombinant IL-2 but optimal triggering of CD8 CTL-precursor required viable tumour stimulator cells. This well characterized in vitro assay may be useful (i) for monitoring the immune status of CD4 and CD8 immune T cells separately, for instance of tumour bearing and/or treated animals and (ii) for the development and testing of potent tumour cell vaccines with T cell stimulatory and/or co-stimulatory activities.
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PMID:Tumour-specific CTL response requiring interactions of four different cell types and recognition of MHC class I and class II restricted tumour antigens. 790 Nov 50

The contribution of dendritic cells (DC) in the initial priming of CD4+ T lymphocytes in vivo was examined. To assess the capacity of different APC to prime CD4+ T cells, a series of MHC class II I-E transgenic mice that differentially express I-E on APC were utilized. Transgenic mice that express I-E primarily on DC, on macrophages, and on B cells were primed with an I-E restricted peptide in vivo, and the extent of priming was determined by restimulation of CD4+ T cells in vitro with the same Ag. The results indicate that DC are required for priming of CD4+ T cells, and that the extent of priming correlates with the frequency of I-E+ DC. Moreover, DC alone can serve as APC for the peptide Ag, in that priming can be restored in an I-E negative mouse by the transfer of peptide-pulsed I-E+ DC. The potency of DC, compared with B cells and macrophages, to prime naive CD4+ T cells was confirmed with in vitro studies.
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PMID:Role of dendritic cells in the priming of CD4+ T lymphocytes to peptide antigen in vivo. 790 97

The Ag, pigeon cytochrome c, was coupled to human ferric transferrin by a heteroligation technique to target Ag into the endosomal transport pathway via transferrin receptors. The ability of various types of APC that do or do not express transferrin receptors to process exogenous Ag in their endosomes was investigated by the stimulation of Ag-specific CD4+ T cells with the transferrin-Ag conjugate in a serum-free assay. When two B lymphoma cells were the source of APC, the conjugate was significantly more potent than native Ag in activating the T cells, agreeing with our previous finding using a third B lymphoma cell. The conjugate and Ag were similarly presented by splenic B cells that lack transferrin receptors to the T cells. However, both a macrophage hybridoma and a MHC class II-L cell transfectant hardly elicited a T cell response to the conjugate, although a response to native Ag was readily observed. These findings could not be attributed to an absence of transferrin receptors or receptor-mediated internalization of the conjugate, nor to differential expression of MHC class II molecules or li chain by the APC. The poor presentation of the conjugate by the L cell transfectants was associated with diminished catabolism of the conjugate, however, the macrophage hybridoma rapidly degraded the conjugate, similar to the B lymphoma cell. Peritoneal macrophages, which lack transferrin receptors, and the macrophage hybridoma induced a response to the conjugate only at concentrations that allowed internalization by fluid phase pinocytosis. The lower potency of the conjugate compared with native Ag with non-B-presenting cells suggest that these cell types process the conjugate by a different mechanism than used by B cells. Differences in the mechanism of Ag processing used by APC of distinct cell lineages may possibly influence immune responsiveness.
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PMID:Differences among various lineages of antigen-presenting cells in processing exogenous antigen internalized through transferrin receptors. 790 98

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