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

Abstract

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.