Get with the program: regulation of T cell death

Programmed cell death (PCD) encompasses several tightly regulated molecular signalling pathways, leading to the controlled destruction of cells. Apoptosis is a non-immunogenic form of cell death that regulates homeostasis to cell stressors. In contrast, lytic forms of cell death - necroptosis, pyroptosis, and ferroptosis - promote inflammation, alerting the immune system to danger. As adaptive immune responders, T cells clonally expand in response to antigenic stimulation and rapidly contract following the clearance of infection. While the role of apoptosis in regulating these processes is relatively well understood, evidence for lytic death activity in T cells is emerging. This review provides an update on recent advances in the understanding of PCD pathways in conventional and unconventional T cells in diverse immune contexts.