Constitutive activation of Wnt signaling favors generation of memory CD8 T cells.

T cell factor-1 (TCF-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical Wnt pathway, are known to be critical for normal thymocyte development. However, it is largely unknown if it has a role in regulating mature T cell activation and T cell-mediated immune responses. In this study, we demonstrate that, like IL-7Ralpha and CD62L, TCF-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during T cell responses, being highly expressed in naive T cells, downregulated in effector T cells, and upregulated again in memory T cells. Enforced expression of a p45 TCF-1 isoform limited the expansion of Ag-specific CD8 T cells in response to Listeria monocytogenes infection. However, when the p45 transgene was coupled with ectopic expression of stabilized beta-catenin, more Ag-specific memory CD8 T cells were generated, with enhanced ability to produce IL-2. Moreover, these memory CD8 T cells expanded to a larger number of secondary effectors and cleared bacteria faster when the immunized mice were rechallenged with virulent L. monocytogenes. Furthermore, in response to vaccinia virus or lymphocytic choriomeningitis virus infection, more Ag-specific memory CD8 T cells were generated in the presence of p45 and stabilized beta-catenin transgenes. Although activated Wnt signaling also resulted in larger numbers of Ag-specific memory CD4 T cells, their functional attributes and expansion after the secondary infection were not improved. Thus, constitutive activation of the canonical Wnt pathway favors memory CD8 T cell formation during initial immunization, resulting in enhanced immunity upon second encounter with the same pathogen.

B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and memory cell generation.

B and T lymphocyte attenuator (BTLA) is a negative regulator of T cell activation, but its function in vivo is not well characterized. Here we show that mice deficient in full-length BTLA or its ligand, herpesvirus entry mediator, had increased number of memory CD8(+) T cells. The memory CD8(+) T cell phenotype resulted from a T cell-intrinsic perturbation of the CD8(+) T cell pool. Naive BTLA-deficient CD8(+) T cells were more efficient than wild-type cells at generating memory in a competitive antigen-specific system. This effect was independent of the initial expansion of the responding antigen-specific T cell population. In addition, BTLA negatively regulated antigen-independent homeostatic expansion of CD4(+) and CD8(+) T cells. These results emphasize two central functions of BTLA in limiting T cell activity in vivo.

Memory of Recessions

This paper reviews the evidence on the effects of recessions on potential output. In contrast to the assumption in mainstream macroeconomic models that economic fluctuations do not change potential output paths, the evidence is that they do in the case of recessions. A model is proposed to explain this phenomenon, based on an analogy with water flows in porous media. Because of the discrete adjustments made by heterogeneous economic agents in such a world, potential output displays hysteresis with regard to aggregate demand shocks, and thus retains a memory of the shocks associated with recessions.

Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.

Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.

A test of long memory hypothesis based on self-similarity

This paper develops a new test of true versus spurious long memory, based on log-periodogram estimation of the long memory parameter using skip-sampled data. A correction factor is derived to overcome the bias in this estimator due to aliasing. The procedure is designed to be used in the context of a conventional test of significance of the long memory parameter, and composite test procedure described that has the properties of known asymptotic size and consistency. The test is implemented using the bootstrap, with the distribution under the null hypothesis being approximated using a dependent-sample bootstrap technique to approximate short-run dependence following fractional differencing. The properties of the test are investigated in a set of Monte Carlo experiments. The procedure is illustrated by applications to exchange rate volatility and dividend growth series.

La mort d'Ananias et Saphira (Ac 5,1-11) dans la stratégie narrative de Luc

L'histoire du jugement de Dieu sur Ananias et Saphira (Ac 5.1-11) compte parmi les épisodes les plus pathétiques du livre des Actes. L'art lucanien de la dramatisation atteint ici un sommet. La fin tragique d'Ananias foudroyé par la parole dénonciatrice de Pierre, son enterrement hâtif, puis la venue de Saphira ignorante du drame, son mensonge public suivi de sa mort annoncée sur un ton d'humour noir (5.9b): l'effet pragmatique cherché par le narrateur est programmé par le scénario; il s'inscrit aussi dans le texte lui-même: 'un grand effroi saisit ceux qui l'entendaient' (5.5, 11). L'histoire est destinée à provoquer la crainte.

Saul's Conversion (Acts 9-22-26) and the Multiplication of Narrative in Acts

(Résumé de l'ouvrage) The essays in this collection come from a research symposium involving the universities of Manchester and Lausanne. The essays cover a wide range of mutually-enriching approaches to the study of the Lukan writings. Aspects considered include Luke's use of the term 'Son of Man', his use of scripture, his literary achievements, and the issue of 'godfearers' in Acts.

Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.

Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma development.

Memory in contracts: the experience of the EBRD (1991-2003)

The objective of this paper is to identify the role of memory as a screening device in repeated contracts with asymmetric information in financial intermediation. We use an original dataset from the European Bank for Reconstruction and Development. We propose a simple empirical method to capture the role of memory using the client's reputation. Our results unambiguously isolate the dominant effect of memory on the bank's lending decisions over market factors in the case of established clients.

Entrer dans le monde du récit biblique en suivant l'analyse narrative

L'analyse narrative permet d'apprécier comment une théologie se dit en narrativité. L'analyse narrative fait réaliser que la construction d'une intrigue, le dispositif d'un réseau de personnages ou la gestion de la temporalité sont autant d'indicateurs de l'intention théologique qu'un énoncé kérygmatique ou une confession de foi. C'est rendre justice aux auteurs bibliques que s'instruire des outils dont ils ont usé pour construire leur récit, quand bien même la théorisation narratologique leur était étrangère. Enfin, l'analyse narrative offre un appareil de lecture et un métalangage simple

L'usage du narratif dans le Testament de Joseph

(Résumé de l'ouvrage) Seventeen innovative studies are collected in this volume which has been produced under the aegis of the Centre for Biblical Studies, University of Manchester, and L'Institut des sciences bibliques, Université de Lausanne. The majority of the studies engage with narrative through providing insightful working examples. Building on the many contributions of recent narratological research, for the most part the studies in this collection avoid the technical language of narratology as they present fresh insights at many levels. Some essays focus more on the implied author, some on the implied reader or hearer, and some on the way particular messages are constructed; some of the studies consider how author, message and reader are all interconnected. There are several creative proposals for refining genre definition, from law and wisdom to gospel and apocryphal writings. Some studies highlight the way in which narratives can contain ethical, religious, and cultural messages. Sensitivity to narrative is also shown by some contributors to expose in intruing ways the redactional processes behind the final form of texts. Students of narrative in the ancient world will find much to consider in this book, and others engaged with literary studies more generally will discover that scholars of the worlds of the Bible and Late Antiquity have much to offer them.

Narrativity in Biblical and Related Texts - La narrativité dans la Bible et les textes apparentés

Seventeen innovative studies are collected in this volume which has been produced under the aegis of the Centre for Biblical Studies, University of Manchester, and L'Institut des sciences bibliques, Université de Lausanne. The majority of the studies engage with narrative through providing insightful working examples. Building on the many contributions of recent narratological research, for the most part the studies in this collection avoid the technical language of narratology as they present fresh insights at many levels. Some essays focus more on the implied author, some on the implied reader or hearer, and some on the way particular messages are constructed; some of the studies consider how author, message and reader are all interconnected. There are several creative proposals for refining genre definition, from law and wisdom to gospel and apocryphal writings. Some studies highlight the way in which narratives can contain ethical, religious, and cultural messages. Sensitivity to narrative is also shown by some contributors to expose in intruing ways the redactional processes behind the final form of texts. Students of narrative in the ancient world will find much to consider in this book, and others engaged with literary studies more generally will discover that scholars of the worlds of the Bible and Late Antiquity have much to offer them.

Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation.

Ag-experienced or memory T cells have increased reactivity to recall Ag, and can be distinguished from naive T cells by altered expression of surface markers such as CD44. Memory T cells have a high turnover rate, and CD8(+) memory T cells proliferate upon viral infection, in the presence of IFN-alphabeta and/or IL-15. In this study, we extend these findings by showing that activated NKT cells and superantigen-activated T cells induce extensive bystander proliferation of both CD8(+) and CD4(+) memory T cells. Moreover, proliferation of memory T cells can be induced by an IFN-alphabeta-independent, but IFN-gamma- or IL-12-dependent pathway. In these conditions of bystander activation, proliferating memory (CD44(high)) T cells do not derive from activation of naive (CD44(low)) T cells, but rather from bona fide memory CD44(high) T cells. Together, these data demonstrate that distinct pathways can induce bystander proliferation of memory T cells.