Human memory CCR4+CD8+ T cell subset has the ability to produce multiple cytokines.
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.
Kondo
Takaaki
T
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Takiguchi
Masafumi
M
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054443:Cell Migration Assays; D054414:Chemokine CCL17 / Q000276:immunology* / Q000378:metabolism; D054422:Chemokine CCL22 / Q000096:biosynthesis* / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D054398:Receptors, CCR4 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D016207:Cytokines; D007376:Interleukin-2; D054398:Receptors, CCR4; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D015847:Interleukin-4; D053804:Granzymes