Human memory CCR4+CD8+ T cell subset has the ability to produce multiple cytokines

Int Immunol. 2009 May;21(5):523-32. doi: 10.1093/intimm/dxp019. Epub 2009 Mar 4.


The CC chemokine receptor (CCR)4 is associated with trafficking of specialized cutaneous memory type 2 T(h) cells in the skin. However, a CD8(+) T cell population expressing CCR4 still remains uncharacterized. In the present study, we investigated the expression and function of CCR4 on human CD8(+) T cells and characterized CCR4(+)CD8(+) human T cells. Multi-color flow cytometric analysis revealed that CCR4(+)CD8(+) T cells were predominantly found in the CD27(+)CD28(+)CD45RA(-) memory subset and expressed the CCR7(+/-)CCR5(-) phenotype. CCR4(+)CD8(+) T cells expressed neither perforin (Per) nor granzymes (Gra) A/B, suggesting that they were more immature memory T cells than the CCR6(+)CD8(+) early effector memory T cells that express GraA and Per. CCR4(+)CD8(+) T cells effectively produced IL-4, IFN-gamma, IL-2 and tumor necrosis factor-alpha, indicating that they are memory T cells having the ability to secrete type 1 and type 2 cytokines. These cells also showed chemotaxic activity in response to CC chemokine receptor ligand (CCL)17/thymus and activation-regulated chemokine and CCL22/macrophage-derived chemokine. These results suggest that CCR4(+)CD8(+) T cells are in an immature memory T cell subset in the differentiation pathway of human CD8(+) T cells and that they migrate to inflammatory sites in the skin where they are involved in cutaneous immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Migration Assays
  • Chemokine CCL17 / immunology*
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / biosynthesis*
  • Chemokine CCL22 / metabolism
  • Chemotaxis / physiology
  • Cytokines / biosynthesis*
  • Granzymes / immunology
  • Granzymes / metabolism
  • Humans
  • Immunologic Memory / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / immunology
  • Perforin / immunology
  • Perforin / metabolism
  • Receptors, CCR4 / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • CCL22 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Cytokines
  • Interleukin-2
  • Receptors, CCR4
  • Tumor Necrosis Factor-alpha
  • Perforin
  • Interleukin-4
  • Granzymes