(Left) When effector T cells receive TCR stimulation, they undergo rapid proliferation accompanied by AICD, limiting expansion. When antigen-stimulation persists, cells eventually become terminally differentiated, apoptotic, or dysfunctional. (Right) Intense, acute, and chronic stimulation screens reveal factors regulating either common or specific T cell fitness traits.Dap5depletion in activated T cells stimulates global mRNA translation, upregulates cell cycle gene activity, and suppresses FAS expression, allowing cell pool expansion under all three stimulation conditions.Icam1ablation or Icam-LFA1 interaction blockade prevents T cell hyperclustering upon stimulation, allowing increased exposure to stimulation signals. This contributes to their stronger cytotoxicity and expansion, especially after intense and acute stimulation. On the contrary,Ctbp1depletion does not influence T cell expansion in the short run, but benefits their long-term persistence and functionality exclusively under chronic stimulation. It exerts this effect by hindering CTBP1/ZEB2/T-bet co-regulated effector terminal differentiation.
