Vleeshouwers et al. showed that the time of antigen encounter determines the differentiation of antigen-specific CD8+ T cells and antiviral immunity. In mice vaccinated with mRNA-1273, active-phase (dark period for mice [nocturnal]) immunization favored progenitor-like memory CD8+ T cells and enhanced T cell-mediated protection against SARS-CoV-2 infection, whereas resting-phase vaccination skewed toward effector-memory phenotypes. The molecular circadian clock in DCs, rather than in CD8+ T cells, regulated time-of-day-dependent CD8+ T cell differentiation and function through CD70–CD27 costimulatory signaling, independent of CD28.
Contributed by Shishir Pant
(1) Vleeshouwers W (2) van Duikeren S (3) de Graaf JF (4) Veerkamp DMB (5) Linger ME (6) Jorritsma SHT (7) Myeni SK (8) Kervezee L (9) Arens R
Vleeshouwers et al. showed that the time of antigen encounter determines the differentiation of antigen-specific CD8+ T cells and antiviral immunity. In mice vaccinated with mRNA-1273, active-phase (dark period for mice [nocturnal]) immunization favored progenitor-like memory CD8+ T cells and enhanced T cell-mediated protection against SARS-CoV-2 infection, whereas resting-phase vaccination skewed toward effector-memory phenotypes. The molecular circadian clock in DCs, rather than in CD8+ T cells, regulated time-of-day-dependent CD8+ T cell differentiation and function through CD70–CD27 costimulatory signaling, independent of CD28.
Contributed by Shishir Pant
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.
Author Info:
(1) Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (2) Department of Immunology, Leiden University Medical Center, Alb
inusdreef 2, 2333 ZA Leiden, The Netherlands. (3) Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (4) Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (5) Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (6) Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (7) Leiden University Center for Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. (8) Department of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands. (9) Department of Immunology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
