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)

We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, C15, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and anti-OVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CD5, and TCR-alpha/beta. Three of the seven clones used TCR-V beta 4. However, the V beta expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-gamma. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.
 ...
PMID:Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. 146 Feb 94

Small, resting human peripheral blood T cells are able to mediate anti-CD3 redirected lysis against murine P815 cells transfected with human B7, a ligand of CD28. We demonstrate that cytotoxicity is mediated by preexisting cytotoxic effectors within the small, resting "memory" T cell population and by the de novo generation of additional CTL within both the "memory" and "virgin" T subsets. This conclusion is based on analysis of the kinetics of the response and the effects of metabolic inhibitors on the generation of CTL function. Memory CD45RO+ T cells demonstrated cytotoxicity within 4 h of coculture with anti-CD3 mAb and B7+ P815 cells and cytolysis was only partially prevented by inhibitors of protein synthesis. By contrast, virgin CD45RO- T cells demonstrated anti-CD3-induced lysis against B7+ P815 targets only after 6 or 8 h of coculture and cytotoxicity was completely prevented by inhibiting protein synthesis. Induction of cytotoxicity was B7 dependent in that parental P815 cells and P815 cells transfected with CD72 and vascular cell adhesion molecule-1, ligands for T cell-associated membrane receptors CD5 and very late activation antigen-4, respectively, did not initiate cytotoxicity. Our studies also revealed cooperation between the CD28/B7 and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1 pathways in the generation of CTL from small, resting T cells. However, after CTL generation, the CD28-B7 interaction was not required for cytotoxic effector cell function. These observations may have important physiologic implications because this would permit activated CTL to lyse targets in vivo that do not express B7, after the CTL were generated by APC that do express B7 or possibly other costimulatory molecules.
 ...
PMID:Requirements for CD28-dependent T cell-mediated cytotoxicity. 838 16

We have analyzed the response of rat T cells to myelin basic protein (MBP) and the bacterial superantigen, staphylococcal enterotoxin E (SEE). Rat T cells reactive with MBP can respond to SEE presented by spleen cells but not to SEE presented by LOA, a rat T cell clone that expresses both I-A and I-E MHC class II molecules, even though LOA is much more efficient than splenic APC in the presentation of MBP. The inability of LOA to present superantigen is not due to a structural difference in MHC II molecules between LOA and the splenic APC or to differential expression of major accessory/adhesion molecules, including CD2, CD5, CD4 and CD44, on LOA. The non-responsiveness of SEE/LOA-induced T cells differs from anergy, in that such cells do not lose their subsequent responsiveness to either MBP or SEE. Our results demonstrate that: (i) MHC class II molecules (I-A and I-E) alone are insufficient for the activation of T cells by bacterial superantigen, (ii) failure to respond to antigen presented upon inappropriate APC or in inadequate doses may not necessarily represent anergy, and (iii) the quality of the T cell response towards certain ligands can be strongly influenced by the nature of the APC.
 ...
PMID:An MHC class II-expressing T cell clone presenting conventional antigen lacks the ability to present bacterial superantigen. 852 5

Best's vitelliform macular dystrophy is an autosomal dominant disorder of unknown causes. To identify the underlying gene defect the disease locus has been mapped to an approximately 1.4-Mb region on chromosome 11q12-q13.1. As a prerequisite for its positional cloning we have assembled a high coverage PAC contig of the candidate region. Here, we report the construction of a primary transcript map that places a total of 19 genes within the Best's disease region. This includes 14 transcripts of as yet unknown function obtained by EST mapping and/or cDNA selection and five genes mapped previously to the interval (CD5, PGA, DDB1, FEN1, and FTH1). Northern blot analyses were performed to determine the expression profiles in various human tissues. At least three genes appear to be good candidates for Best's disease based on their abundant expression in retina or retinal pigment epithelium. Additional information on the functional properties of these genes, as well as mutation analyses in Best's disease patients, have to await their further characterization. [The GenBank/EMBL accession numbers and details of the isolation, localization, and characterization of ESTs and selected cDNAs are available as online supplements in Online Tables 1-3 at http://www.genome.org.]
 ...
PMID:A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1. 944 87

Receptors that display negative signalling functions on lymphocytes and other cells of the reticuloendothelial system now number about 30. These negative receptors are transmembrane glycoproteins activated by phosphorylation of a tyrosine residue in immunoreceptor tyrosine-based inhibitory motifs that bind various phosphatases to induce dominant negative signals. Since these receptors are armed by the action of activating receptors and inhibit signalling by activating receptors, we have termed them coinhibitory receptors and the negative outcome is coinhibition. Coinhibitory receptors and some inhibitory mediators include FcgammaRIIB, CTLA-4, CD5, CD22, p58/70/140 KIR, gp49B1/gp91, PIRB1-5, LAIR-1, NKB1, Ly49 A/C/E/F/G, NKG2-A/B APC-R, CD66, CD72, PD-1, SHPS-1, SIRP-alpha1, ILT1-5, MIR7, 10, hMIR(HM18), hMIR(HM9), LIR1-3,5,8, Fas (CD95), TGFbeta-R, TNF-R1, IFNgamma-R (alpha and beta chains), mast cell function Ag, H2-M, HLA-DM, CD1, CD1-d, CD46, c-cbl, Pyk2/FADK2, P130 Ca rel prot, PGDF-R, LIF, LIF-R, CIS, SOCS13 and 5, and others are being defined regularly. This long list suggests that coinhibitors are needed not only for self-nonself discrimination, but also for control of ongoing responses to foreign antigens so that infectious agents are ideally dealt with by an appropriate level of immune responses to nonself and an appropriate amount of immunopathology and sickness behaviour.
 ...
PMID:Why so many coinhibitory receptors? 1040 45

Autoreactive thymocytes can be deleted at an immature stage of their development by Ag-induced apoptosis or negative selection. In addition to Ag, negative selection also requires costimulatory signals from APC. We recently used a fetal thymus organ culture system to show that CD5, CD28, and TNF cooperatively regulate deletion of autoreactive thymocytes. Although these experiments provided strong evidence for the action of several costimulators in negative selection, we wished to demonstrate a role for these molecules in a physiologically natural model where thymocytes are deleted in vivo by endogenously expressed AGS: Accordingly, we examined thymocyte deletion in costimulator-null mice in three models of autoantigen-induced negative selection. We compared CD5(-/-) CD28(-/-) mice to CD40L(-/-) mice, which exhibited a profound block in negative selection in all three systems. Surprisingly, only one of the three models revealed a requirement for the CD5 and CD28 costimulators in autoantigen-induced deletion. These results suggest that an extraordinarily complex array of costimulators is involved in negative selection. We predict that different sets of costimulators will be required depending on the timing of negative selection, the Ag, the signal strength, the APC, and whether Ag presentation occurs on class I or class II MHC molecules.
 ...
PMID:Requirement for a complex array of costimulators in the negative selection of autoreactive thymocytes in vivo. 1134 22

CD123(bright) plasmacytoid cells (PC) and CD1c(+) peripheral blood myeloid dendritic cells (DC) are two human DC precursors that can be expanded in vivo by Fms-like tyrosine kinase 3 ligand (FL). It has been proposed that PC and myeloid CD1c(+) DC may represent two distinct lineages of DC. However, the phylogenetic affiliation of PC and its relationship with myeloid DC remain controversial. Here we show that CD123(bright)HLA-DR(+) PC from FL-treated healthy volunteers can be divided into mutually exclusive subsets that harbor either lymphoid or myeloid features. Lymphoid-like PC represent the majority of PC and include pTalpha-, CD3epsilon-, and CD7-expressing cells. They exhibit TCR-beta gene loci in germline configuration and show low allostimulatory capacity, but produce type I IFN upon virus infection and can be differentiated in vitro into potent APC. Myeloid-like PC represent a minor fraction of the total PC population. They exhibit a striking PC/myeloid DC intermediate phenotype (CD5(+)CD11c(low)CD45RA(low)CD45RO(-)CD101(+)), produce proinflammatory cytokines, and do not require in vitro maturation to act as potent APCs. We propose that, rather than forming a lineage, PC might represent a population of lymphoid cells undergoing an in vivo cell fate conversion from a lymphoid to a myeloid cell type.
 ...
PMID:CD123bright plasmacytoid predendritic cells: progenitors undergoing cell fate conversion? 1207 31

Physiologically, Ag detection by T cells occurs at the immunological synapse (IS) formed at the interface with an APC. CD5 is considered as an inhibitory molecule for Ag receptor-mediated signals in T cells. However, the influence of CD5 at the IS on synapse formation and functioning has not yet been reported. We demonstrate here that CD5 is recruited and tightly colocalized with CD3 in different human and murine IS. Following transfection in a CD5-negative T cell line of CD5 fused to the green fluorescent protein, we show that CD5 recruitment includes a fast Ag-independent and a slower Ag-dependent component. In video-imaging recordings of doubly transfected cells, the movements of CD3 and CD5 show similar kinetics, and the amount of CD3 recruited to the synapse is unaffected by CD5 expression. Moreover, APC-T cell adhesion is unchanged in CD5-expressing cells. Despite this, the extent of tyrosine phosphorylation at the synapse and the amplitude of calcium responses induced by Ag recognition are both decreased by CD5. These inhibitions increase with CD5 membrane levels. They also requires the pseudo-immunoreceptor tyrosine-based activation motif expressed in the cytoplasmic domain of the molecule. Thus, CD5 is rapidly recruited at the IS and lowers the T cell response elicited by Ag presentation by targeting downstream signaling events without affecting IS formation.
 ...
PMID:CD5 inhibits signaling at the immunological synapse without impairing its formation. 1270 40

This study describes a double-transgenic model in which monoclonal CD8 F5 T cells are chronically exposed to self Ag (nucleoprotein) in the periphery, but are not affected during thymic development. Chronic exposure of CD8 T cells to their cognate Ag rendered them unable to proliferate or produce cytokines in response to antigenic stimulation in vitro. However, the cells still retained some killer function in vivo and continuously eliminated APC expressing high levels of Ag. In addition, when crossed with mice expressing Ag in the anterior pituitary gland (triple-transgenic mice), F5 T cells migrated to this site and killed growth hormone producing somatotrophs. The anergic state was reversible upon transfer into Ag-free recipients, resulting in full recovery of in vitro responsiveness to Ag. Anergic CD8 T cells express higher levels of CD5, a negative regulator of T cell signaling, whereas after transfer and residence in Ag-free hosts, CD5 levels returned to normal. This suggests that up-regulation of negative T cell regulators in peripheral T cells exposed to chronic stimulation by Ag may prevent full functionality and thus avoid overt autoreactivity.
 ...
PMID:Chronic exposure to low levels of antigen in the periphery causes reversible functional impairment correlating with changes in CD5 levels in monoclonal CD8 T cells. 1287 16

The diagnosis of classical Hodgkin lymphoma (CHL) has been made in tissue sections as attempts to identify neoplastic Hodgkin and Reed Sternberg (HRS) cells in lymph nodes by flow cytometry (FC) have been unsuccessful. However, we have recently demonstrated that HRS cells can be identified by FC, often present as T-cell-HRS-cell rosettes. In this study, we examined the usefulness of a novel 9-color (CD95-Pacific blue/CD64-fluorescein isothiocyanate/CD30-phycoerythrin [PE]/CD45-PE-Texas red/CD40-PE cyanine [Cy]5.5/CD20-PECy7/CD15-allophycocyanin [APC]/CD71-APC-AlexaFluor A700/CD5-APC-Cy7), single tube FC assay to diagnose CHL in lymph nodes. We used the FC assay to determine diagnostic sensitivity and specificity in 279 blindly identified and 141 selected (for specimen type or cytopreparation morphologic features suggesting CHL) tissues. Of the 53 morphologically defined CHL cases identified (10 in the unselected group; 43 in the selected group), the FC assay diagnostic sensitivity and specificity were 88.7% and 100%, respectively. With the current availability of 8 (or more) color clinical flow cytometers, this assay can now be applied to routinely immunophenotype and confirm a diagnosis of CHL or as an adjunct to immunohistochemical analysis.
 ...
PMID:Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity. 1922 36


1 2 Next >>