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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Figure 5

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Characterization of activating NK receptors’ internalization following t...
Characterization of activating NK receptors’ internalization following target recognition. (A) Time-dependent percentages of surface levels of NKp30, NKp46, NKG2D, and CD16 receptors on fixed and nonfixed ANK cells. (B) Modulating NKp30 and NKp46 surface expression following ligand-specific recognition. ANK cells (50 × 103) were incubated with an equal number of 721.221 cells at 37_C for 150 minutes. The figure shows time-dependent changes in the percentages of surface levels of NKG2D, NKp46, and NKp30. (C) Downregulation of NKG2D following interaction with its ligands. ANK cells (50 × 103) were incubated with an equal number of C1R transfectants, or with control C1R (C1R mock). The figure shows time-dependent changes in the percentages of expression of NKG2D following specific interaction with its ligands. (D and E) The same coculturing conditions described in B and C, respectively, were applied. Subsequently, NK cells were permeabilized and stained for total expression (intracellular plus surface) of NKp30, NKp46, and NKG2D. The figure displays total cellular expression levels of these receptors following ligation with their specific ligands.