Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent study indicated that all the insulin autoimmune syndrome (IAS) patients had specific HLA class II alleles, the DRB1*0406, DQA1*0301, and DQB1*0302, which allowed T cells to proliferate when autologous APC were exposed to human insulin. The study implied that gene products of DRB1*0406, DQA1*0301, and/or DQB1*0302 may be involved in the presentation of human insulin to T cells. We therefore examined T cell response of healthy donors with different HLA phenotypes to human insulin using an autologous MLR system. The T cells from not only IAS patients but also healthy donors were able to proliferate after exposure of human insulin to autologous APC with DRB1*0406, DQA1*0301, and DQB1*0302 products. The class II molecules are considered to be involved in the recognition of human insulin by T cells. The proliferative response of T cells was completely blocked by anti-HLA-DR mAb and not by anti-HLA-DQ mAb or other mAb. Furthermore, human insulin-specific CD4-positive T cell clones were established from blast cells in autologous MLR of PBMC from two healthy donors with DRB1*0406 in the presence of human insulin. Using DRB1*0406-transfected L cells as APC, we confirmed that these T cells clones recognize human insulin in the context of gene products of DRB1*0406. These results provide the first evidence that HLA-DRB1*0406 products act as the dominant restriction element for the presentation of human insulin to T cells, and suggest that this particular class II gene, HLA-DRB1*0406, contributes to the development of IAS.
 ...
PMID:Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors. 822 61

The capacity of human peripheral blood (PB) dendritic cells (DC) and monocytes to facilitate T cell activation and the interaction molecules employed were compared. We have shown that precursors of DC constitute 2 to 3% of circulating PBMC, and can be isolated as CD33+CD14dim cells, whereas monocytes are CD33+CD14bright. Freshly obtained DC expressed similar densities of HLA-DR and the accessory molecules LFA-3, ICAM-1, and B7 as monocytes; after a 36-h incubation the expression of HLA-DR, ICAM-1, and B7 increased on both APC. Accessory cell function was examined in PB T cell cultures stimulated by suboptimal concentrations of immobilized mAb to CD3, and by stimulation of an allospecific T cell line. Freshly isolated monocytes and DC were comparable accessory cells in these assays, but their accessory function was increased by in vitro preincubation, although cultured DC and monocytes were comparably active. In contrast, DC were much more effective stimulators of freshly isolated allogeneic T cells than monocytes. DC were much more effective stimulators of freshly isolated allogeneic PB CD4+ naive and memory T cells than monocytes, whereas DC and monocytes were comparable accessory cells for memory and naive T cells stimulated with immobilized anti-CD3. The accessory molecules ICAM-1, LFA-3, and B7 were used comparably by DC and monocytes for accessory function in the presence of immobilized anti-CD3 and in the MLR, and none was unique for either APC population. These accessory molecules costimulated T cells in an additive fashion. Although immature blood DC and monocytes expressed minimal B7 and did not utilize it as an accessory molecule, B7 played an important role in the increased accessory function of differentiated APC. The results indicate that PB DC and monocytes function most efficiently after differentiation into mature cells that express increased amounts of MHC and other accessory molecules. Because DC and monocytes exhibit comparable accessory function in anti-CD3 T cell stimulation, differences in the expression of MHC molecules and/or their bound peptides are likely to explain the markedly enhanced capacity of DC to stimulate allogeneic PB T cells.
 ...
PMID:Comparative accessory cell function of human peripheral blood dendritic cells and monocytes. 825 94

Little is known regarding the identification, classification, and function of class II MHC+ dendritic cells in the perivasculature of human connective tissues, such as the dermis. We developed a method for preparing papillary dermal cell suspensions from human keratome strips. Among the class II MHC+ populations of the dermis identified using triple color flow cytometry, cells of monocyte/macrophage lineage (CD45+ CD1- CD11b+ CD11clo-mid CD32+ CD36+ or - CD11a-) and mesenchymal cells of non-bone marrow origin (CD45-) were identified and characterized. Another distinct class II MHC+ subset was identified, which expressed a number of features analogous to epidermal Langerhans cells (LC) and other dendritic APC. These were a numerically minor population comprising only 2.7% +/- 1% (n = 7) of dermal cells. Like LC, they express HLA-DR, CD45, CD1a (albeit at a lower level of expression), CD1c, and CD32 and lack constitutive CD11a or ICAM-1. In contrast to LC, this dermal CD1a+CD1c+ subset expresses CD1b, CD11b, a higher level of CD11c, and intracytoplasmic factor XIIIa. Alloantigen presentation by unfractionated dermal cells was reduced by prior removal of this CD1b+ subset to the same degree achieved by removal of the entire DR+ population (20% of dermal cells), indicating that this was the critical DR+ subset. Cocultures of CD4+ T lymphocytes with cells sorted by flow cytometry into CD1c+DR+, CD1c-DR+ and DR- dermal cell subsets positively identified the CD1c+DR+ population as the most potent of potential APC subsets in human dermis. Thus, in distinction to other dermal macrophage and mesenchymal subsets with elongate morphology, the CD1aloCD1b,c+CD11c(hi)CD11b+CD32+DR+ population in human dermis is highly analogous to cells of LC/dendritic APC lineage in its phenotype and in its exclusive ability to potently present Ag to T lymphocytes. These studies identify and characterize the APC subset most potent in inducing activation of T cells initially entering the perivasculature of human dermis to be of LC/dendritic APC, and not tissue macrophage, lineage.
 ...
PMID:Heterogeneous populations of class II MHC+ cells in human dermal cell suspensions. Identification of a small subset responsible for potent dermal antigen-presenting cell activity with features analogous to Langerhans cells. 840 86

Although peripheral blood eosinophils express little of the class II MHC protein, HLA-DR, eosinophils could be induced to express HLA-DR by exposures to cytokines, including granulocyte-macrophage-CSF, IL-4, and IFN-gamma, with granulocyte-macrophage-CSF eliciting the greatest level of HLA-DR expression as assessed by flow cytometry. The capacity of HLA-DR+ eosinophils to function as APC was evaluated with blood eosinophils isolated free of mononuclear cells, cultured with granulocyte-macrophage-CSF to induce HLA-DR expression and then exposed to the Ag tetanus toxoid. HLA-DR+ eosinophils fixed with paraformaldehyde after Ag exposure stimulated T cell proliferation, whereas HLA-DR+ eosinophils fixed with paraformaldehyde before Ag exposure failed to stimulate lymphocyte proliferation. The lymphocyte proliferative responses elicited by Ag-pulsed HLA-DR+ eosinophils were inhibited by anti-HLA-DR mAb and were restricted to HLA-DR compatible lymphocytes. Moreover, eosinophils from a hypereosinophilic donor, both before and more prominently after stimulation with PMA, contained transcripts for IL-1-alpha mRNA detectable by Northern blot hybridization and in situ hybridization and expressed IL-1-alpha protein detectable by immunohistochemistry. These findings indicate that human eosinophils can process Ag, express the costimulatory cytokine IL-1-alpha, and after cytokine-elicited induction of HLA-DR expression can function as HLA-DR-dependent, MHC-restricted APC in stimulating T lymphocyte responses.
 ...
PMID:Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression. 845 Feb 30

An important and yet unresolved question concerns the mode of T cell recognition of idiotypic epitopes on immunoglobulin molecules in humans. Results from murine and human studies show that some idiotype-specific T cells recognize conformational epitopes on immunoglobulin, and such T cells are not MHC-restricted. In the present study T cell stimulation induced by idiotypic determinants on the autologous monoclonal IgG (M-components) from patients with monoclonal gammopathies was studied. In parallel, T cell stimulation in response to a conventional antigen, purified protein derivative, was also examined. It is shown that, as with conventional antigen, idiotype-induced T cell stimulation requires the presence of antigen-presenting cells (APC; monocytes and/or B cells), and is MHC class II (DR)-restricted. B cells, but not monocytes, can present idiotypic determinants to T cells at very low antigen concentrations, while monocytes do so only when antigen is present at high concentrations. Antigen processing and presentation is abrogated by treatment of APC with chloroquine. In conclusion, our study demonstrates that human idiotype-specific T cells recognize processed idiotypic determinants presented by MHC class II (HLA-DR) molecules on APC, and that B cells require about 1000-fold less antigen that monocytes.
 ...
PMID:Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules. 862 33

This paper shows that the seven HA306-320 specific T-cell clones isolated from one individual recognize the peptide complexed to both autologous HLA-DRB1*1101 and allogeneic HLA-DRB1*1601 (or DRB5*0201) molecules. For each T-cell clone, a single T-cell receptor (TCR) is involved in the recognition of these two different peptide-DR complexes as evidenced by cold target competition experiments. Yet, the seven T-cell clones express several different TCRs as judged by V beta-J beta usage and fine specificities. Furthermore, one representative clone has the same fine specificity for HA306-320 analogues mutated at epitopic residues irrespective of the use of DR1101 or DR1601 APC. These results suggest that structural differences between DRB1*1101 and DRB1*1601 (or DRB5*0201) do not dramatically influence the orientation of HA306-320 in the grooves such that most residues interacting with TCRs are conserved. In another individual, the same pattern of restriction, i.e. DR1101 + DR1601, was found for several HA306-320 specific clones. Two additional patterns, DR1101 + DR0801 and DR1101 + DR0801 + DR1601, were identified. By comparing DR sequences the authors found that DRB1*1101 and DRB1*1601 share four important motifs, i.e. beta 85-86, beta 67-71, beta 57 and beta 28-31 supposed to line three distinct HLA-DR pockets. Three of these motifs are also shared with DRB1*0801. All the results further support that the motif similarities allow the peptide to adopt very similar orientations in the cross-reacting DR molecules.
 ...
PMID:Sharing of four DR-beta sequence motifs between HLA-DRB1*1601 and DRB1*1101 correlates with frequent degenerate T-cell recognition of HA306-320 peptide complexed to these two molecules. 863 94

In this paper, the results of some recent studies on idiotype-specific T cells in human multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are discussed. By using different in vitro measurements such as 3H-thymidine incorporation and ELI-SPOT assay, idiotype-specific T cells have been demonstrated in most of MM and MGUS patients. Based on the cytokine-secretion profiles, idiotype-specific T cells were found to comprise both Th1 and Th2 cells. A Th1 type immunity was found preferentially in indolent disease and a Th2-like response predominated in advanced MM, suggesting a specific T-cell regulation of the tumor B-cell clone. The mode of T-cell recognition of id determinants on M-components has been studied. We found that idiotype-specific T cells recognized processed id determinants presented by MHC class II (HLA-DR) molecules on APC. B cells were much more efficient APC than monocytes. With the aim to induce or to amplify an idiotype-specific T-cell response, we have immunized MM patients with the autologous M-component precipitated in aluminum. Three out of the five patients showed an induction of specific cellular and humoral immunity. Nevertheless, the role for such immunity in controlling the tumor clone remains to be established.
 ...
PMID:Idiotype-specific T cells in multiple myeloma: targets for an immunotherapeutic intervention? 886 33

Microglial cells are resident cells of the CNS and are implicated as regulators and effectors of immune responses which occur within this compartment. The precise role of parenchymal microglia remains speculative because distinctions between these cells, perivascular "microglia," and blood-derived monocytes/macrophages are not well defined. The current study describes the phenotype and function of microglia immediately upon isolation from the non-inflamed adult human CNS and the phenotypic changes which occur in these cells when maintained in tissue culture. We find that the characteristic phenotype of immediately ex vivo parenchymal microglia (CD11c+/CD45low/CD14) corresponds to that found in situ in the "normal" human brain. The phenotype differs from that of perivascular "microglia" in situ and PBDM (both CD45hi/CD14++). The immediately ex vivo microglia express B7-2 and HLA class II molecules and can support alloantigen-induced proliferation by CD4+ T cells freshly isolated from peripheral blood. Following in vitro culture, the cells are characterized by a bipolar morphology, continued lower levels of CD45 expression compared to PBDM, and slight upregulation of B7-1 and HLA-DR antigen expression. CD14 becomes expressed at high levels on the cells, suggesting that CD14 can serve as an apparent marker of microglia activation which is not based on changes in morphology or APC capacity. Further, treatment of the cells with IFN-gamma and LPS causes further upregulation of HLA-DR and clear expression of B7-1 molecules on the surface. The capacity to characterize phenotypic and functional properties of microglia before and after activation provides an opportunity to determine means to manipulate the immune regulatory and effector properties of this cell type.
 ...
PMID:Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. 889 87

In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). Fc epsilon RI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of Fc epsilon RI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti Fc epsilon RI monoclonal antibody. In addition, an Fc epsilon RI positive population was demonstrated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DRHi) and co-express CD 1 a molecules, which identifies them as LC-like dendritic APC of the dermis. No other Fc epsilon RI positive population was found in the other dermal DRMid or DR- populations, except for a minor DRLo population, presumably mast cells. To analyze whether these Fc epsilon RI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of Fc epsilon RI was measured with flow cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DRHiCD1a + cells changed their intracellular calcium level after Fc epsilon RI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following Fc epsilon RI engagement.
 ...
PMID:Expression, but lack of calcium mobilization by high-affinity IgE Fc epsilon receptor I on human epidermal and dermal Langerhans cells. 898 Oct 26

T cell receptor (TCR) triggering via superantigens induces decreased proliferative responses and increased apoptosis in T cells from HIV-infected patients compared with controls. Our aim was to delineate the role of intrinsic T cell defects, of APC dysfunction and of cytokines and costimulatory signal dysregulation in the deficient responses of CD4+ and CD8+ T cells from HIV+ subjects to the superantigen Staphylococcus enterotoxin A (SEA). Proliferation and IL-2R alpha up-regulation on SEA-stimulated CD4+ and CD8+ T cells in whole blood were reduced in HIV+ subjects with CD4 counts < 500, compared with controls. Neither addition of IL-2, IL-12 or phorbol myristate acetate (PMA) nor neutralization of endogenous IL-10, tumour necrosis factor-alpha (TNF-alpha), TNF-beta or transforming growth factor-beta (TGF-beta) could restore the decreased activation by SEA. Possible intrinsic T cell defects were studied by presenting SEA on HLA-DR-transfected Chinese hamster ovary (CHO) cells, co-expressing LFA3 and/or CD80, to purified T cells. In this system CD8+ T cells from most HIV+ patients were hyporesponsive with regard to IL-2 production, IL-2R alpha up-regulation and proliferation, whereas clearly reduced responses were only shown in CD4+ T cells from AIDS patients. Similarly, apoptosis was increased in CD8+ T cells from all patients, but only in CD4+ T cells from AIDS patients. During HIV infection, the responses to TCR triggering through SEA are deficient in both T cell subsets. The intrinsic defect appears earlier during disease progression in purified CD8+ T than in CD4+ T cells, it occurs in conjunction with both CD2 and CD28 costimulation, and it is correlated with increased levels of apoptosis.
 ...
PMID:Superantigen activation of CD4+ and CD8+T cells from HIV-infected subjects: role of costimulatory molecules and antigen-presenting cells (APC) 947 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>