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International Immunology Advance Access originally published online on March 4, 2009
International Immunology 2009 21(5):523-532; doi:10.1093/intimm/dxp019
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Takaaki Kondo and Masafumi Takiguchi

Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan

Correspondence to: M. Takiguchi; E-mail: masafumi{at}kumamoto-u.ac.jp

The CC chemokine receptor (CCR)4 is associated with trafficking of specialized cutaneous memory type 2 Th 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.

Keywords: cell differentiation, chemokines, cytotoxic T cells, human, memory

Transmitting editor: T. Saito

Received 22 July 2008, accepted 4 February 2009.


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