Two Subsets of Memory T Lymphocytes With Distinct Homing Potentials and Effector Functions

Nature. 1999 Oct 14;401(6754):708-12. doi: 10.1038/44385.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • L-Selectin / metabolism
  • Leukopoiesis
  • Lymphocyte Activation
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Receptors, CCR7
  • Receptors, Chemokine / immunology*
  • Receptors, Lymphocyte Homing / metabolism
  • T-Lymphocyte Subsets / immunology*

Substances

  • CCR7 protein, human
  • Receptors, CCR7
  • Receptors, Chemokine
  • Receptors, Lymphocyte Homing
  • L-Selectin
  • Interferon-gamma