Dynamic differentiation of activated human peripheral blood CD8+ and CD4+ effector memory T cells

Two functionally different memory T cell subsets were originally defined based on their different CCR7 expression profile, but the lineage relationship between these subsets referred to as central memory T cells (T-CM) and effector memory T cells (T-EM), is not resolved. A prevalent model proposes a linear progressive differentiation from T-CM to T-EM. Our results demonstrate that on activation, human CCR7(-)CD62L(-) peripheral blood CD8(+) and CD4(+) T,m cells exhibit a dynamic differentiation, involving transient as well as stable changes to T-CM phenotype and properties. Whereas the larger fraction of T,m cells increases expression of effector molecules, such as perforin or IFN-gamma a smaller fraction first acquires CCR7 expression. We demonstrate that this acquisition of lymph node homing potential is associated with strong proliferation similar to that of activated T-CM cells. After proliferation, most of these cells lose CCR7 expression again and acquire effector functions (e.g., perforin production). A small proportion (similar to 6%), however, maintain phenotypic and functional T-CM properties over a long time interval. These results suggest that T-CM cells provide immediate effector function by a fraction of cells as well as self-renewal by others through up-regulation of CCR7 followed by either secondary peripheral effector function or long term maintenance of T-CM-like properties.