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 brightCD11c+ under the conditions used in this study. CD56brightCD11c+ cells were derived from a culture of CD56intCD11c+ 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 CD56brightCD11c+ 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-/intCD11chigh 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 brightCD11c+ cells play a key role in the IL-18-mediated proliferation of γδ T cells. Copyright © 2011 by The American Association of Immunologists, Inc.
Tsuda, J., Li, W., Yamanishi, H., Yamamoto, H., Okuda, A., Kubo, S., … Okamura, H. (2011). Involvement of CD56brightCD11c+ Cells in IL-18-Mediated Expansion of Human T Cells. The Journal of Immunology, 186(4), 2003–2012. https://doi.org/10.4049/jimmunol.1001919