Fig. 1.
CD8+ T cell exhaustion states. CD8+ T cell exhaustion is thought of as a gradual process, with various functional and phenotypic states, including TPE and TEX states. The TPE phenotype is characterized by the expression of TCF1, which is lost upon differentiation into TEX cells. Cell surface markers identified on TPE cells include Slamf6, PD1, and CXCR5, and their functional capacity comprises the ability to produce an antigen-specific immune response, persist long-term, self-renew, and eventually differentiate into TEX cells. In contrast, TEX cells expresses mostly coinhibitory cell surface receptors and transcription factors associated with effector and exhausted cells, including CX3CR1, PD1, CD39, and TIM3, which reflects the functional capacity of TEX cells, that is, mostly cytotoxic functions. TEX cells: terminally exhausted T cells, TPE cells: progenitor STEM-like exhausted cells, TCF1: transcription factor 1