KLRG1+ Memory CD8 T cells Combine Properties of Short-lived Effectors and Long-lived Memory

CD8 effector T cells with a CD127hi KLRG1- phenotype are considered precursors to the long-lived memory pool, while KLRG1+ CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+ CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells or LLEC) display robust protective function during acute re-challenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. Here, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. Furthermore, we find that LLEC are exclusively derived from day 12 KLRG1+ effector cells. Our work challenges the concept that the KLRG1+ CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell. This study includes 15 samples (5 groups in triplicate) analyzed by bulk RNA sequencing. These samples consist of various splenic memory CD8 T cell subsets collected from mice 90 days post infection and analyzed. The study also includes 2 single cell RNA sequencing samples taken at day 12 and day 60 post infection. The study also includes 2 samples (no sample replicates) of splenic memory CD8 T cells captured at 12 or 60 days post infection and analyzed as a large population of single cells using scRNAseq methods.