Notch signalling shapes the CD8 T cell response following Listeria infection (P1416)

Abstract

Abstract Following an infection, naïve CD8 T cells expand and differentiate into effectors able to eliminate the pathogen. At the peak of the response, two populations of effectors are distinguishable: short-lived effector cells (SLECs) meant to die by apoptosis and memory precursor effector cells (MPECs) destined to survive as memory cells that will confer long-term protection. Thus, following activation, the CD8 T cell faces a binary cell fate decision. We postulate that the Notch signalling pathway, known for its role in cellular differentiation and binary cell fate choice, acts as a key player in the MPEC/SLEC choice. To elucidate the role of Notch signalling in CD8 T cell response, we infected mice lacking or not expression of Notch1 and Notch2 in mature CD8 T cells with Listeria monocytogenes expressing OVA. Notch deficiency led to the generation of more OVA-specific effector CD8 T cells but less of these effectors had a SLEC phenotype (CD127loKLRG1hi) at the peak of the response. Surprisingly, Notch did not impair CD8 T cell memory generation following infection. Thus, Notch signalling influences the expansion and the acquisition of a SLEC phenotype following Listeria infection but not the generation of memory cells. Understanding the molecular pathways leading to memory generation is crucial as this knowledge will ultimately contribute to new vaccine development.