Four functionally distinct populations of human effector-memory CD8+ T lymphocytes

J Immunol. 2007 Apr 1;178(7):4112-9. doi: 10.4049/jimmunol.178.7.4112.


In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected the functional properties of ex vivo effector-memory (EM) CD45RA-CCR7- T lymphocytes present within the circulating CD8+ T cell pool of healthy individuals. Our studies show that EM T cells are heterogeneous and are subdivided based on differential CD27 and CD28 expression into four subsets. EM(1) (CD27+CD28+) and EM(4) (CD27-CD28+) T cells express low levels of effector mediators such as granzyme B and perforin and high levels of CD127/IL-7Ralpha. EM(1) cells also have a relatively short replicative history and display strong ex vivo telomerase activity. Therefore, these cells are closely related to central-memory (CD45RA-CCR7+) cells. In contrast, EM(2) (CD27+CD28-) and EM(3) (CD27-CD28-) cells express mediators characteristic of effector cells, whereby EM(3) cells display stronger ex vivo cytolytic activity and have experienced larger numbers of cell divisions, thus resembling differentiated effector (CD45RA+CCR7-) cells. These data indicate that progressive up-regulation of cytolytic activity and stepwise loss of CCR7, CD28, and CD27 both characterize CD8+ T cell differentiation. Finally, memory CD8+ T cells not only include central-memory cells but also EM(1) cells, which differ in CCR7 expression and may therefore confer memory functions in lymphoid and peripheral tissues, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD28 Antigens / genetics
  • CD8-Positive T-Lymphocytes / classification*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Granzymes / genetics
  • Humans
  • Immunologic Memory*
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Male
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins / genetics
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, CCR6
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / genetics
  • Receptors, Interleukin-7 / analysis
  • T-Lymphocyte Subsets / classification*
  • T-Lymphocyte Subsets / immunology*
  • Telomere / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics


  • CCR6 protein, mouse
  • CD28 Antigens
  • Interleukin-7 Receptor alpha Subunit
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, CCR6
  • Receptors, Chemokine
  • Receptors, Interleukin-7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • interleukin-7 receptor, alpha chain
  • Perforin
  • Granzymes