Figure 1.

Model of post-thymic CD8⁺ T cell differentiation. According to this model, after activation of naïve T cells (T_N) during priming, early activated effector T cells (T_EA) receive signals driving functional differentiation to effector T cells (T_EFF) and memory T cells (T_MEM) depending on the recognition of antigen, costimulation, and the inflammatory milieu. In contrast, persistent antigen stimulation, reduced costimulation in the presence of coinhibitory signals and prolonged exposure to inflammatory cues are main drivers of the differentiation toward the exhausted T cell (T_EX) fate, including an up-regulation of inhibitory receptors (IRs).