PIM kinase control of CD8 T cell protein synthesis and cell trafficking

Abstract

Integration of kinase signalling networks co-ordinates the transcriptional, translational, and metabolic changes required for T cell activation and differentiation. This study explores the role of the Serine/Threonine kinases PIM1 and PIM2 in controlling mouse CD8 T lymphocyte antigen receptor-mediated activation and differentiation in response to the cytokines Interleukin-2 (IL-2) or IL-15. We show that the PIM kinases are dispensable for antigen-receptor and IL-15 controlled differentiation programs, but that they play a selective role in IL-2 regulated CD8 T cell fate. One key insight was that PIM kinases controlled the migratory capabilities of effector CD8 T cells, with Pim1/Pim2-deficient CD8 T cells unable to fully switch off the naive T cell chemokine and adhesion receptor program during effector differentiation. PIM kinases were also needed for IL-2 to sustain high expression of the glucose transporters SLC2A1 and SLC2A3 and to maintain activity of the nutrient-sensing kinase mTORc1. Strikingly, PIM kinases did not have a dominant impact on IL-2-driven transcriptional programs but rather selectively modulated protein synthesis to shape cytotoxic T cell proteomes. This study reveals a selective role of PIM kinases in IL-2 control of CD8 T cells and highlights how regulated changes in protein synthesis can impact T cell phenotypes.

Keywords

• T cell
• PIM kinase
• proteomics
• protein translation
• IL-2
• IL-15