Concepts of activated T cell death

Lymphocytes of the adaptive immune system play a crucial role in defending the organism against pathogens. Initial stimulation via antigen receptors induces activation and proliferation of lymphocytes to generate effector cells that clear the pathogen from the body. During the shut-down of the immune response activated lymphocytes are removed by two mechanisms. T cells that are restimulated during the end of the immune response die by activation-induced cell death (AICD), whereas activated lymphocytes which are not restimulated die by activated cell autonomous death (ACAD). Here, we discuss the regulation of AICD and ACAD in T cells and review the role of cytokines, T cell receptor (TCR) proximal signaling mediators like hematopoietic progenitor kinase 1 (HPK1) and the NF-κB pathway. We distinguish between AICD dependent on or independent of death receptor ligation, and discuss caspase-independent death of T cells.