TLR2 engagement on CD8 T cells enables generation of functional memory cells in response to a suboptimal TCR signal.

International audienceTLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal

Integrated platform for home services using new products and services for senior citizens Call CNAV-CARSAT 2015.

International audienceThis project is part of: i) the risks of ageing prevention policy of the French retirement and occupational health insurance agency of Languedoc Roussillon (Carsat-LR) and ii) the European innovation partnership on active and healthy ageing (EIP on AHA). It aims to support senior citizens who live independently and have been identified at risk of frailty on a social or health level. The purpose is to increase legibility as well as technical and financial access to innovations for vulnerable seniors who are remote from the digital era, through a multiservice user-friendly platform. Launched at the end of 2015, the project rallies over 10 actors of the silver economy currently developing personalised ICT tools to improve the safety and comfort of seniors and the coordination between health and social care. The objective is threefold: i) developing new adapted technologies, ii) having them evaluated by retirees and professionals and iii) making them accessible to the ICT web platform which will provide tutorials and prices and collect opinions from users and professionals. 500 retirees selected by CARSAT-LR will be testing these new devices and solutions which will be provided without charge. The following will be evaluated: i) feedback from users; ii) benefits gained through accessing comprehensive and appropriate information; iii) coordination of caregivers and professionals; iv) enjoyment from using the products (access to games, social links, customer confidence, sense of safety). This is a unique opportunity to mobilise solutions in a structured manner, bringing together competing businesses under a consortium agreement. Advantages for these businesses include acceleration of development and availability of their adapted solutions as well as the possibility to test their products on a significant panel of people. Professional caregiver's data follow-up will identify seniors at risk of frailty, proposing preventive actions and local services tailored to their needs

Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions.

International audienceMost memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122(int) memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-gamma secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122(high) memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis

Le site de référence du Partenariat européen d’innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon)

International audienceLe site de référence du Partenariat européen d'innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon