Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

Naive T lymphocytes travel to T-cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells(1,2). Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues(3-6). A fraction of primed T lymphocytes persists as circulating memory cells that can confer protection and give, upon secondary challenge, a qualitatively different and quantitatively enhanced response(7-9) The nature of the cells that mediate the different facets of immunological memory remains unresolved. Here we show that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets, CCR7(-) memory cells express receptors for migration to inflamed tissues and display immediate effector function. In contrast, CCR7(+) memory cells express lymph-node homing receptors and lack immediate effector function, but efficiently stimulate dendritic cells and differentiate into CCR7(-) effector cells upon secondary stimulation. The CCR7(+) and CCR7(-) T cells, which we have named central memory (T-CM) and effector memory (T-EM), differentiate in a step-wise fashion from naive T cells, persist for years after immunization and allow a division of labour in the memory response.