engleski

NKG2D promotes CD8 memory T cell formation by modulating PI3K signaling and enhancing survival of memory precursors

Memory T cell formationa is the result of an intricate balance between extracellular cues and intracellular signaling components. NKG2D (coded by Klrk1) is an activating receptor which potentiates cytotoxic cell function by stimulating PI3K pathway. On CD8 T cells its expression is induced after activatio, but long before target tissues are encountered. In this study, we investigated whether NKG2D and PI3K signaling are involved in the formation and maintenance of CD8 memory T cells. We show that upon viral infection, NKG2D does not only enhance cytotoxicity of effector cells, but also mediateds memory CD8 T cell formation. In vivo, NKG2D requires DAP10 to promote memory cell formation in a process that involves IL15. In vitro, we demonstrate that NKG2D potentiates IL-15 mediated PI3K signaling in a narrow timeframe after activation, early during memory cell differentiation. Inhibition of PI3K or NKG2D signaling during the stage resulted in cell death of memory precursor cells and impaired memory formation. NKG2D deficiency, using Klrk1-/- cells, was accompanied by a more overt effector cell phenotype and reduced survival of cells uder conditions that promote memory differentiation. In conclusion, we demonstrate a novel and crucial role for PI3K-mediated survival signaling early during memory cell differentiation, which is controlled by the IL15/NKG2D axis. Our findings provide new insights in how these receptors may control both cytotoxicity and memory T cell differentiation.

NKG2D; CD8 T cell memory; PI3K

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