NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via PI3K
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1
Faculty of Medicine, University of Rijeka, Croatia
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2
University Medical Center of the Johannes Gutenberg–University Mainz, Germany
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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
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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