Letter | Published:

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

Nature volume 402, pages 3438 (16 December 1999) | Download Citation

Abstract

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 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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Acknowledgements

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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  1. *Basel Institute for Immunology, Grenzacherstrasse 487, Postfach, CH-4005 Basel, Switzerland

    • Federica Sallusto
    • , Danielle Lenig
    •  & Antonio Lanzavecchia
  2. †Max-Delbrueck-Center for Molecular Medicine, Robert Rossle Strasse 10, 13122  Berlin-Buch, Germany

    • Reinhold Förster
    •  & Martin Lipp

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Correspondence to Federica Sallusto.

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https://doi.org/10.1038/35005534

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