Down-regulation of CXCR4 expression on human CD8+ T cells during peripheral differentiation

Eur J Immunol. 2004 Dec;34(12):3370-8. doi: 10.1002/eji.200425587.


Multi-color flow cytometric analysis on human CD8(+) T cell subsets revealed that CXCR4 is predominantly expressed on CD8(+) T cells with the naive CD27(+)CD28(+)CD45RA(+) phenotype, and is down-regulated during differentiation into those with an effector phenotype. The down-regulation of CXCR4 expression during peripheral differentiation was supported by the fact that the expression of CXCR4 on CD8(+) T cells was negatively correlated with that of perforin. The analysis of CCR5, CCR7, and CXCR4 co-expression further showed that CD8(+) T cells expressing a high level of CXCR4 are CCR7(+)CCR5(-) naive or central memory subsets, and those expressing a low level of CXCR4 were included in the CCR7(-)CCR5(+/-) memory/effector and effector subsets. Epstein Barr virus-specific CD8(+) T cells, which mostly express the memory phenotype, expressed CXCR4, while human cytomegalovirus-specific CD8(+) T cells, which mostly express the effector phenotype, partially expressed this receptor, showing that the expression of CXCR4 is also down-regulated during differentiation of viral antigen-specific CD8(+) T cells. The classification of human CD8(+) T cells based on the expression of these chemokine receptors should prove useful for studies that clarify the differentiation of human CD8(+) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Down-Regulation
  • Humans
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism
  • Receptors, CCR7
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism*
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism
  • Receptors, Interleukin-8A / immunology
  • Receptors, Interleukin-8A / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • CCR7 protein, human
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Receptors, CCR5
  • Receptors, CCR7
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Receptors, Interleukin-8A
  • Perforin