Submitted January 26, 2009
Accepted April 27, 2009
NK cell-mediated killing of target cells triggers robust antigen-specific T cell-mediated and humoral responses
Philippe Krebs, Michael J. Barnes, Kristin Lampe, Karen Whitley, Keith S. Bahjat, Bruce Beutler, Edith Janssen, and Kasper Hoebe*
The Scripps Research Institute, Department of Genetics, La Jolla, CA, United States
Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Division of Molecular Immunology, Cincinnati, OH, United States
Robert W Franz Cancer Center, Earle A Chiles Research Institute, Providence Portland Medical center, Portland, OR, United States
* Corresponding author; email: kasper.hoebe{at}cchmc.org.
Previous work showed that administration of antigen-expressing apoptotic cells in vivo results in antigen-specific CD8+ T cell responses independent of TLR signaling. We report here that NK cells can serve a function directly upstream of this pathway and initiate robust adaptive immune responses via killing of antigen-expressing target cells. This pathway is highly sensitive, in that administration of as few as 104 target cells induced detectable antigen-specific CD8+ T cell responses. Importantly, NK cell-mediated cytotoxicity of target cells could also induce robust antigen-specific CD4+ T cell responses, which were critical for subsequent CD8+ T cell priming and IgG responses. Unlike adaptive immune responses induced by 
-irradiated cells, the NK cell pathway required MyD88 and Trif signaling.
NK cells have previously been shown to detect and kill pathogen-infected host cells, as well as neoplastic cells and tissue allografts. The current data provide further evidence that they also discharge a strong tie with their relatives in the adaptive immune system. We believe the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development.
