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

Specific and nonspecific Ag-presentation by B cells was examined for the sensitivity to the treatment with emetin, an irreversible protein synthesis inhibitor. For this aim, A20-HL B lymphoma cells expressing surface IgM receptors specific for TNP were used as APC. OVA and TNP-OVA were used as nonspecific and specific Ag, respectively. The treatment with emetin greatly impaired the ability of A20-HL cells to present specific Ag, but not nonspecific Ag, to 42-6A cloned T cells specific for OVA. The ability of the emetin-treated A20-HL cells to present nonspecific Ag indicates that the treated cells are able to process nonspecific Ag and to present processed Ag. Ag binding and the internalization by A20-HL cells through surface receptors were not affected by the emetin treatment. A20-HL cells took up specific Ag for stimulation of 42-6A cells in the presence of cycloheximide, a reversible protein synthesis inhibitor. These results suggest that the action of emetin is localized to the intracellular processing of specific Ag, not of nonspecific Ag. Thus, the processing pathway for specific Ag seems to be different from that for nonspecific Ag.
J Immunol 1990 Sep 15
PMID:Differential sensitivity of specific and nonspecific antigen-presentation by B cells to a protein synthesis inhibitor. 239 15

To examine the effects of theophylline toxicity on cardiac rhythm, patients underwent continuous ambulatory ECG recording during acute theophylline toxicity and recovery. The patients, who were recruited form inpatient wards, intensive care units, and emergency departments of a University Medical Center and a Veterans Administration Medical Center, had serum theophylline concentrations (STC) greater than 30 mg/L. There were 14 men and two women with a mean age of 66 years. Fourteen patients had COPD and developed toxicity following long-term theophylline overmedication. Two patients had asthma and ingested an intentional overdose. The STC at the onset of ECG recording ranged from 23 to 67 mg/L. The principal rhythm was sinus in 15 patients; one patient had atrial fibrillation. Sinus tachycardia (heart rate greater than 100/min) was common, and heart rate fell in proportion to STC as toxicity resolved. Supraventricular ectopic beats (SVEs) were noted in seven patients with multiple runs of SVE being present in four. One patient developed multifocal atrial tachycardia (MAT) during toxicity that resolved spontaneously. During the 11 +/- 8 hours of recording during toxicity (STC greater than 20 mg/L), 80 percent of patients had ventricular premature beats (VPBs), 44 percent had paired VPBs, and 25 percent had ventricular runs. One elderly patient with heart disease developed sustained ventricular tachycardia (VT) when STC = 66 mg/L. No other patient had ventricular ectopy that required intervention. During the 10 +/- 6 hours of recording during the "recovery phase" (STC less than 20 mg/L), all patients with VPBs continued to have ectopy; however, the number of VPBs declined significantly. A follow-up 24-hour ECG recording obtained one week after recovery from toxicity in the patient with sustained VT demonstrated marked reduction in the frequency and complexity of VPBs. Patients with frequent (greater than 10/h) or repetitive VPBs were older (p less than 0.05) than those without complex ectopy. There was a trend (p = 0.07) suggesting patients with underlying heart disease were at risk for having complex ventricular ectopy. We conclude that sinus tachycardia, SVE, and VPBs are common among patients with theophylline toxicity; however, sustained ventricular or supraventricular tachyarrhythmias that require antiarrhythmic therapy are uncommon.
Chest 1990 Sep
PMID:Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study. 188 98

Th cell-mediated rapid recognition of foreign Ag and the Ia molecule was studied using azobenzenearsonate-L-tyrosine (ABA-L-tyrosine)-specific Th cells (I-Ak restricted), foreign Ag (ABA-L-tyrosine), and APC (H-2k). Initial transmembrane signals in Th cell hybridomas (2-45-12) and in Th cell lines (A24-17 or A33-7) were monitored by stopped-flow fluorometry with fluorescent probes. It was found that Th cells recognized foreign Ag within 1 s at 25 degrees C on the APC (B10.BR spleen cells or L cells into which I-Ak genes were transferred). Recognition of foreign Ag and the Ia molecule was shown to deliver the initial signals to Th cell hybridomas and T cell lines. First, Th cells had membrane fluidity increased and then calcium was transported from the external medium into the T cells. The initial transmembrane signals to Th cell hybridomas were inhibited by the addition of an anti-I-Ak mAb. None of the initial signals were observed in the absence of either specific foreign Ag or APC.
J Immunol 1988 Sep 01
PMID:T cell-mediated recognition of foreign antigen and the Ia molecule observed by stopped-flow fluorometry. 245 16

Experimental allergic encephalomyelitis (EAE)-susceptible Lew and EAE-resistant Brown Norway (BN) rats and the corresponding MHC congenic strains were examined for their ability to develop clinical and histologic EAE. The ability of T cells from these animals to proliferate in vitro in response to whole guinea pig (GP) myelin basic protein (MBP), rat MBP, and to the major encephalitogenic peptide of GP MBP 66-88 (GP 68-88) was also assessed. We found that Lewis (Lew) was highly susceptible and showed good T cell responses to GP, MBP, rat MBP, and GP 68-88. Lew.1N (BN MHC on Lew background) and BN were not susceptible and T cells from these strains showed significant responses to GP MBP, but not to rat MBP or GP 68-88. Although BN.B1 (Lew MHC on BN background) was not susceptible to actively induced EAE, MBP-specific Lew T cells could transfer severe disease to BN.B1. BN.B1 T cells showed responses to GP-MBP, rat MBP, and GP 68-88 and, when transferred to naive BN.B1 or Lew, induced only mild clinical EAE in both strains. Increasing the number of T cells from BN.B1 had no effect on the severity of clinical symptoms in either recipient, suggesting some deficiency in the T cell repertoire that is necessary for induction of severe EAE. These results suggest that 1) the T cell response to rat MBP and GP68-88 (but not to sites other than 68-88 in GP MBP) is necessary for susceptibility to EAE; 2) the ability to respond to both rat MBP and GP 68-88 is determined by the MHC gene products on APC; and 3) given a permissive MHC, the T cell response that results in EAE is influenced by non-MHC genes.
J Immunol 1988 Sep 01
PMID:Genetic control of the development of experimental allergic encephalomyelitis in rats. Separation of MHC and non-MHC gene effects. 245 18

Brief exposure of influenza virus to pH 5 was found to have extensive effects upon presentation of viral Th cell antigenic determinants. This acidity, comparable to that encountered in host cell endosomes, was known to effect conformational changes in the viral hemagglutinin (HA) which alter the molecule's fusion activity, antigenicity, and susceptibility to enzymes. Three major effects of low pH upon presentation of viral T cell determinants were observed: first, acid pretreatment permitted presentation by pre-fixed APC of two of three linear T cell sites of the HA molecule, bypassing the APC activity required to present untreated virus; second, the two determinants presented in this manner disappeared rapidly from APC surfaces; third, acid-pretreated virus was not efficiently utilized by active APC in the normal pathway of viral antigen presentation. These observations suggest that the pH-induced conformational transition of HA may constitute sufficient processing for certain linear determinants of the molecule and additionally influences the processes involved in the general formation and presentation of viral T cell sites.
J Immunol 1988 Sep 15
PMID:Acid-induced conformational modification of the hemagglutinin molecule alters interaction of influenza virus with antigen-presenting cells. 245 93

Ag-specific and MHC-restricted Th clones of different Ag specificities and MHC haplotypes were tested for their ability to produce soluble factors capable of providing the signals required for B cell activation and IgG antibody production. Each of five Th clones tested generated significant helper activity in supernatants derived from coculture of the T cell clone with specific Ag and syngeneic APC. The same helper activity was detected in supernatants of clones stimulated with immobilized anti-CD3 antibody in the absence of Ag or APC. The secreted helper activity resembled the activity of the intact Th cells in that it was Ag-specific, carrier-hapten-linked and MHC-restricted. These T cell products functioned to activate only those B cells expressing MHC products which corresponded to the specificity of each Th clone. Thus, the specificity of the cell-free T cell product mimicked precisely that expressed by the intact Th cell and presumably mediated by the cell surface TcR. In addition to the apparent presence of specific helper factor in Th clone supernatants, a role for nonspecific lymphokines was also identified in these preparations. Although recombinant or purified IL-4 alone was not sufficient to stimulate hapten-primed B cells to secrete hapten-specific IgG antibodies, mAb specific for IL-4 blocked the induction of antibody secretion by Th cell supernatant. These results indicate that stimulation of B cells to produce hapten-specific IgG antibody requires at least two distinct signals: an Ag-specific T cell signal which is restricted by MHC products expressed on the B cells, and a nonspecific signal mediated at least in part by the lymphokine IL-4.
J Immunol 1989 Sep 01
PMID:Antigen-specific, MHC-restricted B cell activation by cell-free Th2 cell products. Synergy between antigen-specific helper factors and IL-4. 247 97

The inductive interaction between class II+ APC and Th cell was investigated in a human system at the chemical level. The study set out to test the predictions of a model of Ag presentation in which epsilon-amino groups and carbonyl groups at the surface of APC and T cell react covalently to form reversible intercellular Schiff bases. In the experimental system of oxidative mitogenesis this process results in T cell activation. If oxidative mitogenesis is an experimental amplification of a physiologic process, and intercellular Schiff base formation is essential in Ag presentation, then it should be possible to inhibit Ag presentation by prior formation of Schiff bases on the surface of participating cells. In this situation Ag-induced T cell activation and T cell activation induced by periodate oxidation should invariably behave in the same way. It should also be possible to demonstrate Schiff base formation occurring between accessory cells and lymphocytes directly and definitively by means of specific reduction with sodium cyanoborohydride. Aldehyde treatment of accessory cells should prevent this intercellular Schiff base formation. In this study the following observations were made. 1) Both Ag-specific and periodate-induced T cell activation were inhibited by aldehyde treatment of class II+ accessory cells. 2) Noncross-linking donors of carbonyl groups other than aldehydes inhibited Ag-specific T cell activation. 3) Brief, low-dose treatment of T cells with aldehydes inhibited Ag-dependent T-cell activation. 4) Exogenous amino groups in the form of lysine and other amino acids inhibited both Ag-specific and periodate-induced T-cell activation. 5) The weak reducing agent sodium cyanoborohydride which is specific for Schiff bases at neutral pH inhibited both Ag-induced and periodate-induced T cell activation. Responses to PHA were markedly prolonged by this reagent. 6) Schiff base formation occurring between accessory cells and lymphocytes was detected directly and definitively by means of radiolabeling with NaCNB(3H)3 at neutral pH. These data are consistent with the view that the formation of reversible covalent Schiff bases between ligands on APC and T cell is an essential process in Ag-induced T cell activation.
J Immunol 1989 Sep 01
PMID:Evidence for an intercellular covalent reaction essential in antigen-specific T cell activation. 247

The choice of class II MHC determinants that serve as self-recognition elements for murine CD4+ T cells is thought to be determined by the environment in which T cells mature rather than their genotype. Patients with severe combined immunodeficiency (SCID) reconstituted with T cell depleted haploidentical parental stem cells provide an excellent model for studying this phenomenon in humans. After engraftment, the T cells that develop in these infants are all of donor origin. We sought to determine whether the successful immune reconstitution observed in two such SCID chimeras involved modification of the MHC restriction of Ag recognition by the genetically donor T cells as they matured to become competent T cells in the infants' microenvironment. A tetanus toxoid (TT)-specific T cell line and TT-specific T cell clones were established from the blood of two reconstituted SCID patients and from their maternal donors. T cell responsiveness was determined by [3H]thymidine incorporation after TT presentation by EBV-transformed B cell lines (EBV-B) from various donors. The TT-specific T cell line from patient 1 proliferated when presented Ag by patient, maternal donor, and paternal APC. A CD4+ donor origin clone that proliferated when presented TT by patient and paternal EBV-B, but not by maternal donor EBV-B, was isolated from each patient. TT recognition by these clones was shown to be restricted by the HLA DR determinant shared by patient and father, but not present in the donor. Four TT-specific clones isolated from maternal donors failed to proliferate when presented TT by the appropriate paternal EBV-B. These studies demonstrate that, in these human SCID bone marrow chimeras, engrafted donor-origin stem cells maturing to competent T cells in the recipient microenvironment are capable of utilizing recipient HLA determinants as restriction elements for Ag recognition. This suggests that human, as well as murine, MHC restriction patterns for Ag recognition by CD4+ T cells are environmentally determined.
J Immunol 1989 Sep 01
PMID:Modified MHC restriction of donor-origin T cells in humans with severe combined immunodeficiency transplanted with haploidentical bone marrow stem cells. 247 4

Alloantigen primed T cells (PTC) were recovered from MLR at day 6 and 12, then added to cultures of erythroid progenitors, erythroid burst-forming units, BFU-E. The PBMC source of BFU-E was prepared either to retain or deplete APC by treatment with appropriate mAb and C. BFU-E grown in cocultures were counted at day 14 and replicate cultures assayed for IFN-gamma production on days 1 to 7. Analysis of MLR cells indicated that large, rapidly cycling cells recovered from MLR at day 6 have significant NK activity, whereas CTL activity is minimal, and production of IFN-gamma requires reexposure to APC. The smaller, noncycling cells recovered from MLR at day 12 have comparable NK activity, also require reexposure to APC for IFN-gamma production, but in addition have significant CTL activity. The addition of day 12 MLR cells to BFU-E cultures results in MHC restricted inhibition of BFU-E growth, suggesting that the CTL activity and not the NK activity contained within this population of cells is responsible for BFU-E inhibition. Studies using enriched population of BFU-E indicated that appropriate APC are needed to trigger both IFN-gamma production and BFU-E inhibition by the PTC. By using various APC-BFU-E combinations it was determined that after reexposure of PTC to appropriate APC, the inhibition of BFU-E was still target-specific indicating a direct effect between the PTC and BFU-E.
J Immunol 1989 Sep 15
PMID:Inhibition of erythroid progenitor growth is mediated by cytotoxic lymphocytes and not by natural killer cells or IFN-gamma. 250 70

The present study investigates the effects of i.v. presensitization with class II H-2-disparate allogeneic cells on various L3T4+ T cell functions including the capability of rejecting the corresponding allogeneic skin graft. C57BL/6 (B6) mice were i.v. presensitized with class II H-2 disparate B6-C-H-2bm12 (bm12) spleen cells. Such presensitization did not affect the bm12-specific L3T4+ T cell-mediated proliferative and interleukin 2 (IL-2)-producing capacities. A single cell suspension of (B6 x bm12)F1 spleen cells was depleted of APC by two round-passages over Sephadex G-10 columns. This APC-depleted fraction of (B6 x bm12)F1 cells failed to stimulate B6 responding cells in mixed lymphocyte reactions (MLR). The addition of recombinant IL-1 to the MLR restored anti-bm12 MLR responses, indicating that APC-depleted (B6 x bm12)F1 cells bear bm12 alloantigens but are unable to stimulate B6 anti-bm12 L3T4+ T cells. A single i.v. administration of APC-depleted (B6 x bm12)F1 cells into B6 mice resulted in almost complete abrogation of the capacity of recipient B6 lymphoid cells to give anti-bm12 MLR and IL2 production. This suppression was bm12 alloantigen-specific and attributed to the elimination or functional impairment of anti-bm12 T cell clones rather than the induction of suppressor cells. The tolerance was also observed in graft-rejection responses. The strikingly prolonged survival of bm12 skin grafts was produced when grafts were implanted into B6 mice which had been presensitized with APC-depleted, but not with untreated (B6 x bm12)F1 spleen cells. These results indicate that allo-class II H-2 antigen-reactive L3T4+ T cells are rendered tolerant by i.v. presensitization with APC-depleted fraction of the corresponding allogeneic cells.
J Immunol 1989 Sep 01
PMID:Tolerance induction of allo-class II H-2 antigen-reactive L3T4+ helper T cells and prolonged survival of the corresponding class II H-2-disparate skin graft. 252 64


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