A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells

Tumor cells treated with IL-10 were shown to have decreased, but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. These findings could be explained, at least partially, by a down-regulation of TAP1/TAP2 expression. In this study, IT9302, a nanomeric peptide (AYMTMKIRN), homologous to the C-terminal of the human IL-10 sequence, was demonstrated to mimic these previously described IL-10 effects on MHC class I-related molecules and functions. We observed a dose-dependent down-regulation of MHC class I at the cell surface of melanoma cells after 24-h treatment with IT9302. The EL-10 homologue peptide also caused a dose-dependent inhibition of the IFN-γ-mediated surface induction of MHC class I in a melanoma cell line. We demonstrated, using Western blot and flow cytometry, that IT9302 inhibits the expression of TAP1 and TAP2 proteins, but not MHC class I H chain or low molecular protein molecules. Finally, peptide-treated melanoma cells were shown to be more sensitive to lysis by NK cells in a dose-dependent way. Taken together, these results demonstrate that a small synthetic peptide derived from IL-10 can mimic the Ag presentation-related effects mediated by this cytokine in human melanomas and increase tumor sensitivity to NK cells, which can be relevant in the designing of future strategies for cancer immune therapy

Avancement du programme : essais de systemes photovoltaiques, mai 1990 - avril 1991

Available at INIST (FR), Document Supply Service, under shelf-number : RP 400 (1644) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Minimum information about tolerogenic antigen-presenting cells (MITAP): a first step towards reproducibility and standardisation of cellular therapies

Contains fulltext : 167331.pdf (publisher's version ) (Open Access)Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and for the prevention of destructive immune responses after transplantation. The methodologies for generating tolAPC vary greatly between different laboratories, making it difficult to compare data from different studies; thus constituting a major hurdle for the development of standardised tolAPC therapeutic products. Here we describe an initiative by members of the tolAPC field to generate a minimum information model for tolAPC (MITAP), providing a reporting framework that will make differences and similarities between tolAPC products transparent. In this way, MITAP constitutes a first but important step towards the production of standardised and reproducible tolAPC for clinical application

Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study

Background: Neuroimaging studies of autosomal dominant Alzheimer's disease (ADAD) enable characterization of the trajectories of cerebral amyloid-beta (A beta) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD.Methods: Fourteen ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2-3 sessions of A beta (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2-4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers.Results: Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with A beta accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (similar to 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers.Conclusions: Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between A beta burden and neocortical tau accumulation in ADAD

Search for invisibly decaying Higgs bosons with large decay width using the OPAL detector at LEP

This paper describes a topological search for an invisibly decaying Higgs boson,H, produced via the Bjorken process (e+e- -> HZ). The analysis is based on data recorded using the OPAL detector at LEP at centre-of-mass energies from 183 to 209 GeV corresponding to a total integrated luminosity of 629pb-1. In the analysis only hadronic decays of the Z boson are considered. A scan over Higgs boson masses from 1 to 120 GeV and decay widths from 1 to 3000 GeV revealed no indication for a signal in the data. From a likelihood ratio of expected signal and Standard Model background we determine upper limits on cross-section times branching ratio to an invisible final state. For moderate Higgs boson decay widths, these range from about 0.07pb Mh = 60GeV) to 0.57pb (Mh = 114GeV). For decay widths above 200GeV the upper limits are of the order of 0.15pb. The results can be interpreted in general scenarios predicting a large invisible decay width of the Higgs boson. As an example we interpret the results in the so-called stealthy Higgs scenario. The limits from this analysis exclude a large part of the parameter range of this scenario experimentally accessible at LEP2.Comment: 30 pages, 10 figures, Submitted to Eur. Phys.

Measurement of the e+ e- →\rightarrow W+ W- cross section and W decay branching fractions at LEP

From a total data sample of 701.1 pb(-1) recorded with e(+)e(-) centre-of- mass energies of root s = 161 - 209 GeV with the OPAL detector at LEP, 11693 W-pair candidate events are selected. These data are used to obtain measurements of the W-pair production cross sections at 10 different centre-of-mass energies. The ratio of the measured cross sections to the standard model expectation is found to be: data/SM = 1.002 +/- 0.011(stat.) +/- 0.007 (syst.) +/- 0.005(theory), where the uncertainties are statistical, experimental systematics and theory systematics respectively. The data are used to determine the W boson branching fractions, which are found to be consistent with lepton universality of the charged current interaction. Assuming lepton universality, the branching ratio to hadrons is determined to be 67.41 +/- 0.37(stat.) +/- 0.23(syst.)%, from which the CKM matrix element |V-cs| is determined to be 0.969 +/- 0.017(stat.) +/- 0.012(syst.). The differential cross section as a function of the W- production angle is measured for the qqev and qq mu v final states. The results described in this paper are consistent with the expectations from the standard model

Search for lepton flavor violation in e+ e- collisions at s**(1/2) = 189-GeV - 209-GeV

We search for lepton flavour violating events (e mu, e tau and mu tau) that could be directly produced in e+e- annihilations, using the full available data sample collected with the OPAL detector at centre-of-mass energies between 189 GeV and 209 GeV. In general, the Standard Model expectations describe the data well for all the channels and at each sqrt(s). A single e mu event is observed where according to our Monte Carlo simulations only 0.019 events are expected from Standard Model processes. We obtain the first limits on the cross-sections sigma(e+e- -> e mu, e tau and mu tau) as a function of sqrt(s) at LEP2 energies.Comment: 15 pages, 4 figures, Accepted by Physics Letters