Transcriptional regulatory network for the establishment of CD8+ T cell exhaustion

Abstract

Immunity: exhausted T cells provide subtle long-term defenses A type of T cell previously thought to be defective could actually provide long-term mild immune responses for combating cancer. The unique environment created during chronic infections gives rise to functionally inert T cells known as ‘exhausted’ cells, which were once thought to impede immune responses. Wooseok Seo and co-workers at Nagoya University and the National Cancer Center in Tokyo, Japan, have reviewed recent studies suggesting that exhausted T cells may be generated by the body to provide mild immune responses. Such responses are safer over the long term than strong inflammatory defense mechanisms, where T cells may be overstimulated, leading to uncontrolled tissue damage and induced T cell death. The signaling pathways that generate and propagate exhausted cells are being revealed, shedding light on the developmental stages that lead to this subtle but effective response to chronic conditions.