Dendritic cell circadian clocks shape memory CD8 + T cell differentiation
Ward Vleeshouwers, Suzanne van Duikeren, J. Fréderique de Graaf, Dominique M. B. Veerkamp, Marissa E. Linger, Sytze H. T. Jorritsma, Sebenzile K. Myeni, Laura Kervezee, Ramon ArensCircadian rhythms regulate diverse immune processes, yet how they influence memory CD8 + T cell differentiation remains unclear. Here, we show that the time of day of antigen encounter shapes CD8 + T cell fate and antiviral immunity. Immunization during the active phase promotes the generation of progenitor-like memory CD8 + T cells and enhances T cell-mediated protection upon viral challenge. Mechanistically, dendritic cell-intrinsic circadian clocks regulate expression of the costimulatory ligand CD70, thereby directing T cell differentiation. These findings uncover a dendritic cell-mediated circadian mechanism that governs memory T cell fate decisions and suggest that aligning immune priming with circadian time may be leveraged to optimize T cell immunity.