Biomedical subjects

Jean-Yves Cesbron

Publications and source records attributed to Jean-Yves Cesbron.

5 recordsLinked to original sources

PubMed2006

Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus.

Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.

Animals↗

PubMed2004

Epidemiological evidence of higher susceptibility to vCJD in the young.

BACKGROUND: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. METHODS: Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. RESULTS: The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. CONCLUSIONS: This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases.

Adolescent↗

PubMed2004

Prion protein (PrPc) immunocytochemistry and expression of the green fluorescent protein reporter gene under control of the bovine PrP gene promoter in the mouse brain.

Expression of the cellular prion protein (PrP(c)) by host cells is required for prion replication and neuroinvasion in transmissible spongiform encephalopathies. As a consequence, identification of the cell types expressing PrP(c) is necessary to determine the target cells involved in the cerebral propagation of prion diseases. To identify the cells expressing PrP(c) in the mouse brain, the immunocytochemical localization of PrP(c) was investigated at the cellular and ultrastructural levels in several brain regions. In addition, we analyzed the expression pattern of a green fluorescent protein reporter gene under the control of regulatory sequences of the bovine prion protein gene in the brain of transgenic mice. By using a preembedding immunogold technique, neuronal PrP(c) was observed mainly bound to the cell surface and presynaptic sites. Dictyosomes and recycling organelles in most of the major neuron types also exhibited PrP(c) antigen. In the olfactory bulb, neocortex, putamen, hippocampus, thalamus, and cerebellum, the distribution pattern of both green fluorescent protein and PrP(c) immunoreactivity suggested that the transgenic regulatory sequences of the bovine PrP gene were sufficient to promote expression of the reporter gene in neurons that express immunodetectable endogenous PrP(c). Transgenic mice expressing PrP-GFP may thus provide attractive murine models for analyzing the transcriptional activity of the Prnp gene during prion infections as well as the anatomopathological kinetics of prion diseases.

Animals↗

PubMed2003

Modelling the epidemic of variant Creutzfeldt-Jakob disease in the UK based on age characteristics: updated, detailed analysis.

Incubation period of the new variant Creutzfeldt-Jakob disease (vCJD) from infection to clinical onset and the eventual impact of the disease remain major concerns. Based on i) epidemiological conceptualization of human exposure to BSE contaminated material, ii) exponentially decreasing susceptibility after 15 years of age, and iii) typical incubation period (IP) distributions for time from infection to onset, we have previously estimated mean incubation period and projected number of vCJD cases. In this paper, we investigate the robustness of these estimates with respect to i-iii using the UK's 113 vCJD cases with clinical onset before December 2000. Mean incubation period was estimated at 16.4 years (95% CI 11.4-24.8), 15.9 years (95% CI 11.4-22.0), 14.1 years (95% CI 10.4-24.2) with the log-normal, Gamma and Weibull distributions respectively. Corresponding predictions for the total size of the epidemic ranged from 183 to 304. Maximal susceptibility to infection between 1.3 and 15.9 years and decreasing by 15% per year of age thereafter yielded the best fit. The shape of the IP distribution did not affect the predictions. In summary, within a set of reasonable assumptions, mean incubation period for vCJD ranged from 15 to 20 years, and the eventual impact of vCJD was a few hundred patients.

Age Factors↗

PubMed2002

PrP expression and replication by Schwann cells: implications in prion spreading.

Prion infection relies on a continuous chain of PrP(c)-expressing tissues to spread from peripheral sites to the central nervous system (CNS). Direct neuroinvasion via peripheral nerves has long been considered likely. However, the speed of axonal flow is incompatible with the lengthy delay prior to the detection of PrP(Sc) in the brain. We hypothesized that Schwann cells could be the candidate implicated in this mechanism; for that, it has to express PrP(c) and to allow PrP(Sc) conversion. We investigated in vivo localization of PrP(c) in sciatic nerve samples from different strains of mice. We demonstrated that PrP(c) is mainly localized at the cell membrane of the Schwann cell. We also studied in vitro expression of PrP(c) in the Schwann cell line MSC-80 and demonstrated that it expresses PrP(c) at the same location. More specifically, we demonstrated that this glial cell line, when infected in vitro with the mouse Chandler prion strain, both produces the PrP(Sc) till after 18 passages and is able to transmit disease to mice, which then develop the typical signs of prion diseases. It is the first time that infection and replication of PrP(Sc) are shown in a peripheral glial cell line.

Animals↗