Novel APC-like properties of human NK cells directly regulate T cell activation
Jacob Hanna, … , Jane H. Buckner, Ofer Mandelboim
Jacob Hanna, … , Jane H. Buckner, Ofer Mandelboim
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1612-1623. https://doi.org/10.1172/JCI22787.
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Article Immunology

Novel APC-like properties of human NK cells directly regulate T cell activation

Abstract

Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane–enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell–mediated cytotoxicity and specific ligand recognition by cell surface–activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell–activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2–deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell–activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.

Authors

Jacob Hanna, Tsufit Gonen-Gross, Jonathan Fitchett, Tony Rowe, Mark Daniels, Tal I. Arnon, Roi Gazit, Aviva Joseph, Karoline W. Schjetne, Alexander Steinle, Angel Porgador, Dror Mevorach, Debra Goldman-Wohl, Simcha Yagel, Michael J. LaBarre, Jane H. Buckner, Ofer Mandelboim

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Enhanced APC-like properties of NK cells after lysis receptor_mediated a...
Enhanced APC-like properties of NK cells after lysis receptor_mediated activation. (A) UaNK cells (100 × 103)were cocultured with multiple target cells at an effector/target ratio of 1:1 for 72 hours. NK cells were purified using magnetic beads and stained for CD56 and either HLA-DR,DP,DQ or CD86. MFI for the latter 2 markers is indicated in each panel. (B) UaNK cells were cultured in triplicate for 72 hours in RPMI medium plus 10% human serum and 30 U/ml human IL-2 and in the presence of the indicated soluble mAbs and were stained for expression of HLA-DR,DP,DQ and CD86. Data are shown as MFI ± SD. Iso con, isotype-matched control. (C) Circulating CD4+ T cells (4 × 106) isolated from HLA-DR4+ donors were incubated with 1 × 106 ANK cells pulsed with 150 ng/ml HA protein per well in 24-well plates. On day 4, half of the wells in each experiment were supplemented with 5 μg/ml of anti-CD16 and anti-NKp46 mAbs. On day 10, cells from each well were stained for CD4 and DR0401-HA or control DR0401-ospA tetramers. The percentage of tetramer-positive fraction out of total CD4+ T cells stained is indicated. (D and E) UaNK cells (D) or ANK cells (E) (0.5 × 106 each) were incubated with noninfected or influenza virus_infected 1106mel cells at an NK/target ratio of 10:1 for 72 hours. The NK cells were repurified with magnetic beads, irradiated, washed, incubated with OFR3 clone cells for 48 hours, and pulsed with thymidine for the last 24 hours. *P < 0.05; **P < 0.01 by Student’s t test. Data are representative of 2_4 independent experiments.