Originally published as Nature 401 , 708–712; 1999 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 , 4 , 5 , 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 , 8 , 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.
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