Effector CD8 T cells dedifferentiate into long-lived memory cells

DNA methyltransferase 3a regulates CD8 T cell memory differentiation Transgenic P14 CD8 T cells were harvested from naïve P14 TCR transgenic mice and 2K P14 cells were adoptively transferred intravenously to congenically distinct C57BL/6 mice one day before acute LCMV infection. Effector P14 CD8 T cells were FACS-purified from spleens of acutely infected mice on days 4.5 and 8 post-infection for whole genome bisulfite sequencing analysis (WGBS), and naïve antigen-specific cells obtained from transgenic P14 mice were used as an antigen-specific naïve control for WGBS. Dnmt3a conditional knockout mice were generated by breeding previously characterized floxed Dnmt3a mice with mice that contain a granzyme b driven recombinase transgene. Dnmt3a cKO and WT C57BL/6 mice mice were acutely infected with LCMV Armstrong strain and gp33-specific CD8 T cells were FACS-purified from spleens of acutely infected mice on day 8 post-infection.