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 cells1,2. Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues3,4,5,6. 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 response7,8,9. 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 (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.

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Figure 1: CCR7 and CD62L are co-expressed on a subset of peripheral blood memory CD4+ and CD8+ T cells.
Figure 2: CCR7+ and CCR7- memory T cells display different effector functions.
Figure 3: Rapid production of IFN-γ following stimulation of CCR7- memory T cells.
Figure 4: CCR7+ memory cells show enhanced responsiveness to T-cell receptor triggering and potently activate dendritic cells to produce IL-12.
Figure 5: Proliferative responses to recall antigens can be detected in both CCR7+ and CCR7- subsets but not in naive T cells.
Figure 6: Differentiation potential of naive and memory T-cell subsets.


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We thank K. Hannestad and K. Karjalainen for critical reading; J. C. Howard for his help as ‘wordsmith’; M. Dessing and A. Pickert for cell sorting; A. Hoy for help in the initial experiments; LeukoSite Inc., Cambridge, Massachusetts for providing antibodies to chemokine receptors; and L. Wu for providing the CCR7 and CCR4 antibodies before publication. The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

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Correspondence to Federica Sallusto.

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