Validierung eines Zytotoxizitaetstests als Ersatzmethode zum Fischtest nach DIN 38412. T. 31, Phase II Abschlussbericht

SIGLEAvailable from TIB Hannover: F97B460+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Signal Integration by Akt Regulates CD8 T Cell Effector and Memory Differentiation

During a T cell response, the effector CTL pool contains two cellular subsets: short-lived effector cells (SLECs), a majority of which are destined for apoptosis, and the memory precursor effector cells, which differentiate into memory cells. Understanding the mechanisms that govern the differentiation of memory CD8 T cells is of fundamental importance in the development of effective CD8 T cell-based vaccines. The strength and nature of TCR signaling, along with signals delivered by cytokines like IL-2 and IL-12, influence differentiation of SLECs and memory precursor effector cells. A central question is, how are signals emanating from multiple receptors integrated and interpreted to define the fate of effector CTLs? Using genetic and pharmacological tools, we have identified Akt as a signal integrator that links distinct facets of CTL differentiation to the specific signaling pathways of FOXO, mTOR, and Wnt/beta-catenin. Sustained Akt activation triggered by convergent extracellular signals evokes a transcription program that enhances effector functions, drives differentiation of terminal effectors, and diminishes the CTLs' potential to survive and differentiate into memory cells. Whereas sustained Akt activation severely impaired CD8 T cell memory and protective immunity, in vivo inhibition of Akt rescued SLECs from deletion and increased the number of memory CD8 T cells. Thus, the cumulative strength of convergent signals from signaling molecules such as TCR, costimulatory molecules, and cytokine receptors governs the magnitude of Akt activation, which in turn controls the generation of long-lived memory cells. These findings suggest that therapeutic modulation of Akt might be a strategy to augment vaccine-induced immunity. The Journal of Immunology, 2012, 188: 4305-4314.X117763sciescopu

Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus

Human pandemic H1N1 2009 influenza virus rapidly infected millions worldwide and was associated with significant mortality. Antiviral drugs that inhibit influenza virus replication are the primary therapy used to diminish disease; however, there are two significant limitations to their effective use: (i) antiviral drugs exert selective pressure on the virus, resulting in the generation of more fit viral progeny that are resistant to treatment; and (ii) antiviral drugs do not directly inhibit immune-mediated pulmonary injury that is a significant component of disease. Here we show that dampening the host's immune response against influenza virus using an immunomodulatory drug, AAL-R, provides significant protection from mortality (82%) over that of the neuraminidase inhibitor oseltamivir alone (50%). AAL-R combined with oseltamivir provided maximum protection against a lethal challenge of influenza virus (96%). Mechanistically, AAL-R inhibits cellular and cytokine/chemokine responses to limit immunopathologic damage, while maintaining host control of virus replication. With cytokine storm playing a role in the pathogenesis of a wide assortment of viral, bacterial, and immunologic diseases, a therapeutic approach using sphingosine analogs is of particular interest

L'Égypte. [3], Ankh / Serge Grave, réal. ; Josette Niel-Poinssac, aut. ; Christiane Desroches-Noblecourt, cons. scient., présent. ; Alain Cuny, voix

Collection : Histoire ancienneCollection : Histoire ancienneRésumé : Le terme ankh serait à l'origine un hiéroglyphe symbole de l'Égypte et plus précisément du Nil, source de vie. Cette émission fixe une tranche de vie de la foule anonyme à l'aide de documents figurés ou écrits. C'est ainsi que sont évoqués : la vie rurale axée sur le régime du fleuve, la vie urbaine liée aux boutiques, aux petits métiers et à l'habitat d'une classe aisée (source : Média-Scérén)Durée : 00:25:10Thème : Histoir