Agenda de l'ENS de Lyon

The encounter of naive CD8 T-cells with antigen presenting cells triggers their activation, proliferation and differentiation up to the memory state. In order to study the early molecular events that are leading to the generation of memory cells we have set-up an in vitro/in vivo model of memory generation. We have first calibrated the in vitro activation conditions and set up the assays to measure cell division, survival and phenotype. To assess the capacity of in vitro activated CD8 T cells to differentiate in memory cells we have established an in vivo transfer system in either naive or virus infected mice.  Our results indicate that cellular concentration strongly impacts the IL-2-dependency of CD8 T cell activation in vitro. Indeed, at high cellular concentration, exogenous IL-2 is redundant to generate effector or memory CD8 T cells.  The presence of exogenous IL-2 becomes essential at lower cell concentration. To characterise the trajectory followed by CD8 T cells following activation in the presence or absence of IL-2 we have performed cell phenotypic and single cell RNA sequence analysis, our result suggest that frequency of memory precursor cells is increased when CD8 are activated in the absence of IL-2. Finally, the role of other gamma c cytokines on the activation of CD8 T cells was also studied, our results suggest that exogenous IL-7 and IL-15 drive a similar differentiation of CD8 as exogenous IL-2, while exogenous IL-4 and IL-21 induce a distinct differentiation-path. 
Key words: CD8 T cell, exogenous IL-2, gamma c cytokines