NKp46 Expression Accelerates the Formation of the NK Cell Lytic Immune Synapse
Div. of Abdominal Transplantation/Dept. of Surgery, Stanford University, Stanford, CA
Dept. of Pediatrics, Stanford University, Stanford, CA
Dept. of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer Sheva, Israel
Meeting: 2013 American Transplant Congress
Abstract number: D1564
Natural killer cells play an important role in first-line defense against tumor and virus-infected cells. Studies suggest NK cells have a dichotomous role in transplantation with evidence supporting the role of NK cells in both graft rejection and tolerance. The activity of NK cells is tightly regulated by a repertoire of cell-surface expressed inhibitory and activating receptors. NKp46 is a major NK cell activating receptor that is involved in the elimination of HCV and other viral infected cells and has been shown to regulate interactions of NK cells with other immune cells including T cells and dendritic cells (DC). Recent studies have shown that DC-mediated activation of NK cells is dependent upon signaling through the NKp46 activation receptor. Rapid advances in microscopy techniques have significantly contributed to our ability to examine and analyze the NK immune synapse, the interface between NK cells and other cells. NK cells can form different types of synapses; cytotoxic, inhibitory, and regulatory. However the distinct nature by which NKp46 participates in NK immune synapse formation and function remains unknown. In this study we use high-resolution microscopy and wild-type NK cells (NK92) or NKp46-overexpressing NK cells (NK92-NKp46) to investigate the function of NKp46 at the immune synapse level. We found that NKp46 is arranged in a cone-shaped structure at the immune synapse between NK cells and target cells. Labeling of F-actin with Rh-Phalloidin showed that higher expression of NKp46 is correlated with increased accumulation of actin mesh at the immune synapse. NK92 cells transfected with NKp46-IRES-GFP in combination with LysoTracker demonstrated that higher expression of NKp46 contributes to rapid polarization of lytic granules toward target cells. We developed a live imaging cytotoxicity assay with NKp46-IRES-GFP expressing NK cells to show that NKp46 expression is correlated with a more rapid lysis of target cells. These results suggest that NKp46 on NK cells activates and regulates cells of the immune system resulting in the promotion or prevention of an alloimmune response. NK cell functions are generally refractory to immunosuppressive drugs thus understating these fundamental aspects of NKp46 function will contribute to our ability to manipulate NK cell activity post-transplant.
To cite this abstract in AMA style:
Hadad U, Thauland T, Butte M, Krams S. NKp46 Expression Accelerates the Formation of the NK Cell Lytic Immune Synapse [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/nkp46-expression-accelerates-the-formation-of-the-nk-cell-lytic-immune-synapse/. Accessed May 10, 2025.« Back to 2013 American Transplant Congress