Figure 3.

T-bet and Eomes partitioning during CD8⁺ T cell priming and expansion. (A) The orientation and strength of TCR/MHC ligation, co-stimulation (e.g., CD28 interaction with CD80 and CD86), CD4⁺ T cell help (CD40L/CD40 licensing of DCs including up-regulation of MHC I, CD80/CD86, CD70, and third signal cytokines), autocrine IL-2 exposure, and innate inflammatory stimuli (danger- and pathogen-associated molecular patterns) all influence the activation, survival, and differentiation of naïve CD8⁺ T cells. (B) CD8⁺ T cells integrate these input events at priming and during the first division. The uneven partitioning of T-bet and Eomes favors SLEC (effector) versus MPEC (memory) differentiation early after activation, respectively. In contrast, the CD8⁺ T_ex lineage requires both transcription factors and retains some features of memory cells including self-renewal of PD-1^lo subsets and expression of memory-associated transcription factors and survival molecules. The reliance on homeostatic cytokines (predominantly IL-7) versus persistent antigen for development and self-renewal distinguishes memory from PD-1^lo/hi exhaustion lineages, respectively.