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

The CD8(+) T cell response to infection is characterized by the appearance of short-lived (CD127(low) killer cell lectin-like receptor G 1-high) and memory-precursor (CD127(high) killer cell lectin-like receptor G 1-low) effector cells. How and when central-memory T (T-CM; CD62L(high) CCR7(+)) cell and effector-memory T(T-EM; CD62L(low) 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 T-CM 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 T-CM/T-EM cell lineage decision ultimately through IL-2 and IL-15 signaling levels. These observations identify key early signals that help establish the T-CM/T-EM cell dichotomy and provide the means to manipulate memory lineage choices. The Journal of Immunology, 2010, 185: 263-272.