Data from: Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8+ T cells

CD8+ T cells rely on actin cytoskeleton remodeling to search for target
cells and assemble the immunological synapse (IS) for lethal hit delivery.
We here investigated how the energy expenditure related to actin
remodeling might influence the fitness of human cytotoxic T cells. We
first established that the spreading ability of CD8+ T cells in conditions
of LFA-1 and TCR engagement mirrored the cytotoxic potential of these
cells. Morphological and functional fitness were both potentiated by IL-2,
which co-stimulated the transcription of glycolytic enzymes, actin
isoforms and the subunits of the ARP2/3 complex. This molecular program
scaled with F-actin content and cell spreading. Blockade of glycolysis
impaired F-actin remodeling at the lamellipodium, chemokine-driven
motility and synaptic adhesion, while blockade of mitochondrial OXPHOS
affected F-actin less severely and selectively reduced cell elongation
during confined migration. Although T cells deficient for the ARP2/3
subunit ARPC1B increased their ATP content upon IL-2 exposure, their
morphological and functional defects were only partially corrected,
pointing to the pivotal position of ARP2/3 mediated actin polymerization
as integrator of T cell energetic state. Our study therefore highlights
that the ability of effector T cells to migrate, form IS and ultimately
kill target cells depends on a tight coordination of their metabolic and
actin remodeling activities.