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Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor
Shino Hanabuchi1, Norihiko Watanabe, Yi-Hong Wang
1Department of Immunology and Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, 7455 Fannin, Unit 910, Houston, 77030-1903, USA.
Abstract:
Plasmacytoid dendritic cell precursors (pDCs) are professional type I interferon-producing cells, a critical cell type in regulating innate and adaptive immune responses. By microarray gene expression analysis, we found that pDCs activated by virus or CpG-ODN preferentially express the ligand for the glucocorticoid-induced tumor necrosis factor receptor (GITRL), which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis. Using the same approaches, we found GITR is expressed by activated natural killer (NK) cells and T cells. We show that pDCs activated by CpG-ODN promote NK cell cytotoxicity and interferon (IFN)-gamma production through type I IFNs and GITRL. Using a GITRL-transfected cell line, we further demonstrate that GITRL promotes NK cell cytotoxicity and IFN-gamma production in synergy with interleukin-2 (IL-2), IFN-alpha, and NKG2D triggering. We also demonstrated that pDCs localized in close contact to NK cells in T-cell areas of the tonsils, and a subpopulation of the pDCs expressed GITRL. This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells.
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