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. Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues. 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. 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 (TCM) and effector memory (TEM), 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.
Sallusto
F
F
Basel Institute for Immunology, Switzerland. sallusto@bii.ch
Lenig
D
D
Förster
R
R
Lipp
M
M
Lanzavecchia
A
A
D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D019041:L-Selectin / Q000378:metabolism; D019891:Leukopoiesis; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D007371:Interferon-gamma