Switching on memory CD8+ T cells for enlarged pathogen-specific protection (P4375)

Abstract

Abstract Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. In recent work, we have shown that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes to become potent effector cells by sensing IL-18 and IL-15-derived inflammatory cytokines from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral and parasitic infections, and contributed to innate responses and protection in vivo. In our most recent experiments, we investigate further the molecular mechanisms of cross-talk between activated memory T cells and innate immune effector cells that allow for pathogen-specific protective immunity. Our results unravel a novel and unexpected level of antigen-dependent spatio-temporal tissue organization that is essential to achieve quick and efficient pathogen confinement and killing. This mechanism depends on memory T cell-derived IFN-γ and chemotactic cues, and on effector monocytes. We will present and discuss these data.