Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL).
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.
Hanabuchi
Shino
S
Department 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.
Watanabe
Norihiko
N
Wang
Yi-Hong
YH
Wang
Yui-Hsi
YH
Ito
Tomoki
T
Shaw
Joanne
J
Cao
Wei
W
Qin
F Xiao-Feng
FX
Liu
Yong-Jun
YJ
D001483:Base Sequence; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014162:Transfection; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
C408982:CPG-oligonucleotide; D053450:Glucocorticoid-Induced TNFR-Related Protein; D009838:Oligodeoxyribonucleotides; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C491405:TNFRSF18 protein, human; C478967:TNFSF18 protein, human; D048069:Tumor Necrosis Factors; D007371:Interferon-gamma; D004247:DNA