CD8 cytotoxic T lymphocytes (CTL) rely on rapid reorganization of the branched F-actin network to drive the polarized secretion of lytic granules, initiating target cell death during the adaptive immune response. Branched F-actin is generated by the nucleation factor Arp2/3 complex. Patients with mutations in the ARPC1B subunit of Arp2/3 show combined immunodeficiency with symptoms of immune dysregulation including recurrent viral infections and reduced CD8 T cell count. Here we show that loss of ARPC1B led to loss of CTL cytotoxicity, with the defect arising at two different levels. First ARPC1B is required for lamellipodia formation, cell migration and actin reorganisation across the immune synapse. Second, we found that ARPC1B is indispensable for the maintenance of TCR, CD8 and GLUT1 membrane proteins at the plasma membrane of CTL, as recycling via the retromer and WASH complexes was impaired in the absence of ARPC1B. Loss of TCR, CD8 and GLUT1 gave rise to defects in T cell signalling and proliferation upon antigen stimulation of ARPC1B-deficient CTL, leading to a progressive loss of CD8 T cells. This triggered an activation-induced immunodeficiency of CTL activity in ARPC1B-deficient patients, which could explain the susceptibility to severe and prolonged viral infections.