Early Signals during CD8+ T Cell Priming Regulate the Generation of Central Memory Cells

Abstract

The CD8+ T cell response to infection is characterized by the appearance of short-lived (CD127low killer cell lectin-like receptor G 1–high) and memory-precursor (CD127high killer cell lectin-like receptor G 1–low) effector cells. How and when central-memory T (TCM; CD62Lhigh CCR7+) cell and effector-memory T(TEM; CD62Llow CCR7−) cell subsets are established remains unclear. We now show that the TCM cell lineage represents an early developmental branchpoint during the CD8+ T cell response to infection. Central-memory CD8+ T cells could be identified prior to the peak of the CD8+ T cell response and were enriched in lymphoid organs. Moreover, the kinetics and magnitude of TCM cell development were dependent on the infectious agent. Furthermore, the extent of early Ag availability, which regulated programmed death-1 and CD25 expression levels, controlled the TCM/TEM cell lineage decision ultimately through IL-2 and IL-15 signaling levels. These observations identify key early signals that help establish the TCM/TEM cell dichotomy and provide the means to manipulate memory lineage choices.