NK cell-mediated regulation of CD8 T cell responses
NK cells are typically known for their role in early detection and killing of “altered self”, including virus-infected and malignant cells. However, there is growing evidence for a role of NK cells in regulating the size of adaptive T cell responses via direct (e.g. direct killing of T cells) and indirect mechanisms (e.g. modulating antigen-presenting cell numbers and function). We have shown that NK cells effectively recognize and kill - via engagement of NCR1 (natural cytotoxicity receptor 1) antiviral CD8 T cells that are unable to sense inflammatory cues during their priming, suggesting that “improperly” activated CD8 T cells are rendered targets for NK cells. We test this hypothesis by addressing the question whether self-reactive CD8 T cells that are recognizing antigen in a non-inflammatory environment are also subject to NK cell mediated control.
Related publications:
Mandaric, S., S. M. Walton, T. Rulicke, K. Richter, M. J. Girard-Madoux, B. E. Clausen, A. Zurunic, M. Kamanaka, R. A. Flavell, S. Jonjic, and A. Oxenius. 2012. IL-10 Suppression of NK/DC Crosstalk Leads to Poor Priming of MCMV-Specific CD4 T Cells and Prolonged MCMV Persistence. PLoS Pathog 8: e1002846. [external pageAbstract]
Crouse, J., G. Bedenikovic, M. Wiesel, M. Ibberson, I. Xenarios, D. Von Laer, U. Kalinke, E. Vivier, S. Jonjic, and A. Oxenius. 2014. Type I Interferons Protect T Cells against NK Cell Attack Mediated by the Activating Receptor NCR1. Immunity 40: 961-973. [external pageAbstract]
Crouse, J., H. C. Xu, P. A. Lang, and A. Oxenius. 2014. NK cells regulating T cell responses: mechanisms and outcome. Trends Immunol. 2015 Jan;36(1):49-58. [external pageAbstract]
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Pallmer, K., and A. Oxenius. 2016. Recognition and Regulation of T Cells by NK Cells. Front Immunol 7: 251. [external pageAbstract]
Pallmer, K., I. Barnstorf, N. S. Baumann, M. Borsa, S. Jonjic, and A. Oxenius. 2019. NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection. PLoS Pathog 15: e1007725. [external pageAbstract]