NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via PI3K

Abstract

Event Abstract Back to Event NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via PI3K Felix M. Wensveen1*, Maja Lenartić1, Vedrana Jelenčić1, Niels A. Lemmermann2, Anja Ten Brinke3, Stipan Jonjić1 and Bojan Polić1 1 Faculty of Medicine, University of Rijeka, Croatia 2 University Medical Center of the Johannes Gutenberg–University Mainz, Germany 3 Sanquin Research, Netherlands Memory formation of activated CD8 T cells is the result of a specific combination of signals that promote long-term survival and inhibit differentiation into effector cells. Much is known about initial cues that drive memory formation, but it is poorly understood which signals are essential during the intermediate stages before terminal differentiation. NKG2D is an activating co-receptor on antigen-experienced CD8 T cells, which promotes effector cell functions. Its role in memory formation is currently unknown. We show that NKG2D controls formation of CD8 memory T cells by promoting survival of precursor cells. We demonstrate that NKG2D enhances IL-15 mediated PI3K signaling of activated CD8 T cells, in a specific phase of memory cell commitment, after activation but before terminal differentiation. This signal is essential for the induction of pro-survival protein Mcl-1 and precursor cell survival. In vivo, NKG2D-deficiency results in reduced memory cell formation and impaired protection against re-infection. Our findings show a new role for PI3K and the NKG2D/IL-15 axis in an underappreciated stage of effector to memory cell transition that is essential for the generation of anti-viral immunity. Moreover, we provide novel insights how these receptors control both effector and memory T cell differentiation. Keywords: NKG2D, Mcl-1, PI3K, CD8 T cell, memory T cell, Survival Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Wensveen FM, Lenartić M, Jelenčić V, Lemmermann NA, Ten Brinke A, Jonjić S and Polić B (2013). NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via PI3K. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00669 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Felix M Wensveen, Faculty of Medicine, University of Rijeka, Rijeka, Croatia, felix.wensveen@medri.uniri.hr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Felix M Wensveen Maja Lenartić Vedrana Jelenčić Niels A Lemmermann Anja Ten Brinke Stipan Jonjić Bojan Polić Google Felix M Wensveen Maja Lenartić Vedrana Jelenčić Niels A Lemmermann Anja Ten Brinke Stipan Jonjić Bojan Polić Google Scholar Felix M Wensveen Maja Lenartić Vedrana Jelenčić Niels A Lemmermann Anja Ten Brinke Stipan Jonjić Bojan Polić PubMed Felix M Wensveen Maja Lenartić Vedrana Jelenčić Niels A Lemmermann Anja Ten Brinke Stipan Jonjić Bojan Polić Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.