Immunity and cytotoxic lymphocytes
CD8 T-lymphocytes are an essential component of adaptive immunity. Their role is to protect the organism against infections by viruses and some bacteria and against tumour development. Naïve CD8 T-cells that are specific for a given antigen represent rare cells that can be found in the blood and secondary lymphoid organs (spleen and lymph nodes). Upon infection or vaccination, naïve cells that are specific for microbial antigens are activated by Dendritic Cells, in the corresponding draining lymph nodes and in the spleen. There, naïve cells proliferate, differentiate into effector cells and migrate to the infection/immunisation site, in order to kill infected cells. Upon clearance of the pathogen, a small fraction of those cells will survive as long-lived memory cells that can protect the organism against subsequent infections. This enhanced protection is conferred by the improved functions of memory cells (in terms of reactivity, cytotoxic activity, cytokines productions, migration), their increased frequency and their modified positioning in the organism.
Projects that are developed in the team are:
– to characterise and model the differentiation of naïve lymphocytes into effector and memory cells
– to identify and characterise distinct subsets of memory CD8 T-cells
– to establish the properties of memory CD8 T cells that associated with immune protection
– to study factors that regulate migration and positioning of CD8 T-cells
Altogether, that knowledge is critical for the development of vaccines whose aim is to induce efficient, T-cells mediated, immune responses. In line with this, we have several on-going translational projects with industrial partners.
– Establishment of a mathematical model describing CD8 T-cells response (Cell System 2017, BMC Syst Biol. 2016).
– Deep characterisation of “innate-like” memory CD8 T-cells (Journal of Immunol. 2018)
– Identification of transcriptomic signatures associated with the capacity of memory CD8 T-cells to protect against a diversity of pathogens (Sci. Report 2016)
– Demonstration that inflammatory signals (GM-CSF or PAMP) stimulate cross-presentation by newly generated DC to CD8 T-cells (Journal of Immunol. 2011, Trends Immunol. 2012).
INSERM, UCBL, CNRS, ANR, FINOVI, ARC, LNCC, REGION