Involvement of CD56brightCD11c+ cells in IL-18-mediated expansion of human γδ T cells.
γδ T cells are considered to be innate lymphocytes that play an important role in host defense against tumors and infections. We recently reported that IL-18 markedly amplified γδ T cell responses to zoledronate (ZOL)/IL-2. In an extension of this finding, we analyzed the mechanism underlying the IL-18-mediated expansion of γδ T cells. After incubation of PBMCs with ZOL/IL-2/IL-18, the majority of the cells expressed γδ TCR, and the rest mostly exhibited CD56(bright)CD11c(+) under the conditions used in this study. CD56(bright)CD11c(+) cells were derived from a culture of CD56(int)CD11c(+) cells and CD14(+) cells in the presence of IL-2 and IL-18 without the addition of ZOL. They expressed IL-18Rs, HLA-DR, CD25, CD80, CD83, CD86, and CD11a/CD18. In addition, they produced IFN-γ, TNF-α, but not IL-12, when treated with IL-2/IL-18, and they exerted cytotoxicity against K562 cells, thus exhibiting characteristics of both NK cells and dendritic cells. Incubation of purified γδ T cells with CD56(bright)CD11c(+) cells in the presence of ZOL/IL-2/IL-18 resulted in the formation of massive cell clusters and led to the marked expansion of γδ T cells. However, both conventional CD56(-/int)CD11c(high) dendritic cells induced by GM-CSF/IL-4 and CD56(+)CD11c(-) NK cells failed to support the expansion of γδ T cells. These results strongly suggest that CD56(bright)CD11c(+) cells play a key role in the IL-18-mediated proliferation of γδ T cells.
Laboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo 663-8501, Japan.
Junko
J
Tsuda
Wen
W
Li
Hiromichi
H
Yamanishi
Hideyuki
H
Yamamoto
Akico
A
Okuda
Shuji
S
Kubo
Zhifeng
Z
Ma
Nobuyuki
N
Terada
Yoshimasa
Y
Tanaka
Haruki
H
Okamura
D000328:Adult; D039521:CD11c Antigen / Q000096:biosynthesis* / Q000502:physiology; D019002:CD56 Antigen / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D020382:Interleukin-18 / Q000502:physiology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D039521:CD11c Antigen; D019002:CD56 Antigen; D020382:Interleukin-18; C522918:NCAM1 protein, human; D016692:Receptors, Antigen, T-Cell, gamma-delta