Acute CD8+ T cell responses to viral infection harbor Tcf1-dependent stem-like cells that quantitatively yield central memory [RNA-seq]

Central memory CD8+ T cells (TCM) can protect from secondary pathogen infection, from chronic infection and cancer as a result of their stem cell-like properties. However, the developmental origin of central memory cells and consequently the basis of their stemness have not been resolved. By monitoring the expression of the transcription factor Tcf1 (Tcf7), which is essential for central memory formation, we identified a small subset of CD8+ T cells present during the acute response to primary infection. These cells lacked cytotoxic effector function, resembled TCM both transcriptionally and epigenetically, had stem cell-like properties, and quantitatively yielded TCM. Stemness effector phase Tcf7+ CD8+ T cells depended on Tcf1 protein expression and on a set of Tcf1-dependent genes associated with adult stem cells. Stemness was thus not acquired subsequent to antigen clearance but was maintained in rare CD8+ T cells responding to acute infection and these cells quantitatively yielded TCM. Overall design: Tcf7GFP P14 cells (either wild-type (Wt) or Tcf7-/- (Ko) (CD45.2+) were flow sorted from the spleen of naive mice based Tcf7GFPhi and CD62L+ (Naive). Naïve Tcf7GFPhi P14 cells were transferred into B6 recipient mice (CD45.1) prior to infection with LCMV Armstrong (Arm). Tcf7GFPhi and Tcf7GFP- P14 cells were flow sortedfrom the spleen on day 8 or day 30 post infection using CD45.1- CD45.2+. Total RNA was extracted, cDNA libraries prepared and sequencing was performed using Illumina HiSeq 2500 technology.