a | The process of arresting T cell development is shown. Differentiation of primed naive T (TN) cells can be suppressed using cytokines, such as interleukin-21 (IL-21), or by using small molecules targeting key metabolic and developmental pathways. b | Two step reprogramming of terminally differentiated effector T (TEFF) cells through an induced pluripotent stem (iPS) cell intermediate is shown. TEFF cells are reprogrammed to generate iPS cells by ectopic co-expression of the Yamanaka factors, and OCT4, sex determining region Y (SRY) BOX 2 (SOX2) and Kruppel-like factor 4 (KLF4) with or without MYC or by forced expression of the microRNA (miRNA) cluster 302–367. iPS cells can be subsequently redifferentiated into TN cells through the induction of NOTCH signalling. c | Direct reprogramming of TEFF into TN or memory stem (TSCM) cells by enforced expression of TN or TSCM-associated transcription factors or miRNAs is shown. GSK3β, glycogen synthase 3β; TCM, central memory; TEM, effector memory.