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NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase (CROSBI ID 202241)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Wensveen, Felix Martinus ; Lenartić, Maja ; Jelenčić, Vedrana ; Lemmermann, N.A. ; ten Brinke, A. ; Jonjić, Stipan ; Polić, Bojan NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase // Journal of immunology, 191 (2013), 3; 1307-1315. doi: 10.4049/jimmunol.1300670

Podaci o odgovornosti

Wensveen, Felix Martinus ; Lenartić, Maja ; Jelenčić, Vedrana ; Lemmermann, N.A. ; ten Brinke, A. ; Jonjić, Stipan ; Polić, Bojan

engleski

NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase

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 coreceptor on Ag-experienced CD8 T cells that promotes effector cell functions. Its role in memory formation is currently unknown. In this study, 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 prosurvival protein Mcl-1 and precursor cell survival. In vivo, NKG2D deficiency results in reduced memory cell formation and impaired protection against reinfection. 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 antiviral immunity. Moreover, we provide novel insights how these receptors control both effector and memory T cell differentiation.

NKG2D; CD8 T cell memory; Mcl1; PI3K

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Podaci o izdanju

191 (3)

2013.

1307-1315

objavljeno

0022-1767

10.4049/jimmunol.1300670

Povezanost rada

Temeljne medicinske znanosti

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