Développement et mécanismes suppresseurs des lymphocytes T régulateurs CD8+CD28low chez la souris

Un des mécanismes qui contribuent à maintenir une tolérance vis-à-vis de ses propres constituants est l'immunosuppression active exercée par des sous-populations lymphocytaires immunorégulatrices. Parmi celles-ci, une population de lymphocytes T (LT) CD8+ régulatrice est caractérisée par un niveau très faible d'expression de la molécule de co-stimulation CD28. Les lymphocytes T régulateurs CD8+CD28low (Treg) fraîchement isolés préviennent le développement d'une maladie inflammatoire intestinale induite par le transfert de cellules T naïves CD4+CD45RBhigh chez la Souris immunodéficiente. L'IL-10 et le TGF-ß sont deux cytokines immunosuppressives indispensables à cette protection. De façon intéressante, un défaut de l'activité suppressive des LT CD8+ (mais pas CD4+) isolés à partir du côlon de patients atteints de maladies inflammatoires chroniques intestinales a été décrit. L'ensemble de ces données suggère un rôle important des Treg CD8+ dans le maintien de l'homéostasie immunologique de l'intestin. La sélection du répertoire des Treg capables d'inhiber l'inflammation intestinale reste inconnue. Nous avons testé la capacité des Treg CD8+CD28low isolés à partir de souris déficientes pour AIRE à prévenir le développement d'une colite expérimentale. Ce facteur de transcription permet l'expression d'antigènes des tissus périphériques dans les cellules épithéliales de la medulla du thymus ainsi que dans les cellules stromales des nœuds lymphatiques et participe ainsi à l'induction d'une tolérance envers les antigènes du soi. Alors que les lymphocytes T CD8+CD28low AIRE-/- sont fonctionnels in vitro, ces cellules sont incapables de prévenir une colite expérimentale. Cette observation suggère fortement qu'AIRE est impliqué dans la sélection des Treg CD8+CD28low et pourrait moduler le TCR-répertoire de cette population. Nous nous sommes également intéressés à l'identification des cibles de l'IL10 ainsi qu'au rôle de l'enzyme IDO (indoléamine 2,3-dioxygénase) dans la protection de la colite expérimentale par les LTreg CD8+CD28low. Une meilleure compréhension des mécanismes d'action et du développement des Treg CD8+CD28low capables de contrôler l'inflammation intestinale devrait ouvrir la voie au ciblage de cette population à des fins thérapeutiques.Immunological unresponsiveness to self and innocuous non-self antigens is in large part assured by regulatory T lymphocytes. While CD4+ T lymphocytes have recently attracted most attention, several CD8+ regulatory T cell populations are also thought to play an important role in immunoregulation. One of these CD8+ populations is characterized by low-level expression of the co-stimulatory molecule CD28. CD8+CD28low regulatory T cells (Treg), freshly isolated from unmanipulated wildtype mice, prevent inflammatory bowel disease (IBD) induced by transfer of CD4+CD45RBhigh T-cells into immunodeficient mice. IL-10 and TGF-ß play a crucial and non-redundant role in prevention of experimentally induced colitis. Importantly, defects in the immunosuppressive activity of CD8+ (but not CD4) cells from colonic biopsies of patients affected by inflammatory bowel disease have been described, suggesting a critical role of CD8+ Treg in the prevention of this pathology. The selection of the Treg TCR-repertoire inhibiting intestinal inflammation remains a largely unexplored issue. We have assessed the capacity of CD8+CD28low Treg isolated from AIRE-deficient mice to prevent experimental colitis. This transcription factor allows for expression of tissue-antigens in thymic medullary epithelial as well as lymph node stromal cells and thereby induces tolerance to self-antigens. Whereas they were fully functional in in vitro suppression assays, AIRE-deficient CD8+CD28low failed to prevent experimental colitis. This observation strongly suggests that AIRE shapes the TCR-repertoire CD8+CD28low Treg. We also searched for the cellular target of Treg-derived IL-10 and assessed the potential role of IDO (indoleamine 2,3-dioxygenase) in the prevention of colitis by CD8+CD28low Treg. A better comprehension of the molecular suppressor mechanisms and of the development of CD8+CD28low Treg involved in control of intestinal inflammation should ultimately lead to development of novel and genuinly curative therapies for the treatment of IBD

Extended RDF: Computability and Complexity Issues

ERDF stable model semantics is a recently proposed semantics for ERDF ontologies and a faithful extension of RDFS semantics on RDF graphs. In this paper, we elaborate on the computability and complexity issues of the ERDF stable model semantics. Based on the undecidability result of ERDF stable model semantics, decidability under this semantics cannot be achieved, unless ERDF ontologies of restricted syntax are considered. Therefore, we propose a slightly modified semantics for ERDF ontologies, called ERDF #n- stable model semantics. We show that entailment under this semantics is, in general, decidable and also extends RDFS entailment. Equivalence statements between the two semantics are provided. Additionally, we provide algorithms that compute the ERDF #n-stable models of syntax-restricted and general ERDF ontologies. Further, we provide complexity results for the ERDF #nstable model semantics on syntax-restricted and general ERDF ontologies. Finally, we provide complexity results for the ERDF stable model semantics on syntax-restricted ERDF ontologies

The DLV System for Knowledge Representation and Reasoning

This paper presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to $\Delta^P_3$-complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof. Furthermore, we illustrate the general architecture of the DLV system which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.Comment: 56 pages, 9 figures, 6 table

Reasoning about actions meets strategic logics (LORI 2013)

International audienceWe introduce ATLEA, a novel extension of Alternating-time Temporal Logic with explicit actions in the object language. ATLEA allows to reason about abilities of agents under commitments to play certain actions. Pre- and postconditions as well as availability and unavailability of actions can be expressed. We show that the multiagent extension of Reiter’s solution to the frame problem can be encoded into ATLEA. We also consider an epistemic extension of ATLEA. We demonstrate that the resulting logic is sufficiently expressive to reason about uniform choices of actions. Complexity results for the satisfiability problem of ATLEA and its epistemic extension are given in the paper

A Note on Vectorial AdS5_5/CFT4_4 Duality for Spin-jj Boundary Theory

The vectorial holographic correspondences between higher-spin theories in AdS$_5$ and free vector models on the boundary are extended to the cases where the latter is described by free massless spin-$j$ field. The dual higher-spin theory in the bulk does not include gravity and can only be defined on rigid AdS$_5$ background with $S^4$ boundary. We discuss various properties of these rather special higher-spin theories and calculate their one-loop free energies. We show that the result is proportional to the same quantity for spin-$j$ doubleton treated as if it is a AdS$_5$ field. Finally, we consider even more special case where the boundary theory itself is given by an infinite tower of massless higher-spin fields.Comment: 27 pages, version to appear in JHE

Dynamics of Higher Spin Fields and Tensorial Space

The structure and the dynamics of massless higher spin fields in various dimensions are reviewed with an emphasis on conformally invariant higher spin fields. We show that in D=3,4,6 and 10 dimensional space-time the conformal higher spin fields constitute the quantum spectrum of a twistor-like particle propagating in tensorial spaces of corresponding dimensions. We give a detailed analysis of the field equations of the model and establish their relation with known formulations of free higher spin field theory.Comment: JHEP3 style, 40 pages; v2 typos corrected, comments and references added; v3 published versio

Ground state properties of a Tonks-Girardeau Gas in a periodic potential

In this paper, we investigate the ground-state properties of a bosonic Tonks-Girardeau gas confined in a one-dimensional periodic potential. The single-particle reduced density matrix is computed numerically for systems up to $N=265$ bosons. Scaling analysis of the occupation number of the lowest orbital shows that there are no Bose-Einstein Condensation(BEC) for the periodically trapped TG gas in both commensurate and incommensurate cases. We find that, in the commensurate case, the scaling exponents of the occupation number of the lowest orbital, the amplitude of the lowest orbital and the zero-momentum peak height with the particle numbers are 0, -0.5 and 1, respectively, while in the incommensurate case, they are 0.5, -0.5 and 1.5, respectively. These exponents are related to each other in a universal relation.Comment: 9 pages, 10 figure

Families of exact solutions to Vasiliev's 4D equations with spherical, cylindrical and biaxial symmetry

We provide Vasiliev's four-dimensional bosonic higher-spin gravities with six families of exact solutions admitting two commuting Killing vectors. Each family contains a subset of generalized Petrov Type-D solutions in which one of the two so(2) symmetries enhances to either so(3) or so(2,1). In particular, the spherically symmetric solutions are static and we expect one of them to be gauge-equivalent to the extremal Didenko-Vasiliev solution given in arXiv:0906.3898. The solutions activate all spins and can be characterized either via generalized electric and magnetic charges defined asymptotically in weak-field regions or via the values of fully higher-spin gauge-invariant observables given by on-shell closed zero-forms. The solutions are obtained by combining the gauge-function method with separation of variables in twistor space via expansion of the Weyl zero-form in Di-Rac supersingleton projectors times deformation parameters in a fashion that is suggestive of a generalized electromagnetic duality.Comment: v1: 77 pages; 3 tables; 23 pages of appendices. v2: 5 additional pages of clarifications, typos correcte