Dendritic cell circadian clocks shape memory CD8⁺ T cell differentiation.

Abstract

Circadian 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.